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The Bioactive Imperative: Why Standardization to Unique Compounds is Essential for Botanical Product Integrity

A Technical White Paper on Quality Standards in the Botanical Supplement Industry

Author: Paul Eftang, President and CEO of Nootropics Depot

December 30, 2025


Executive Summary

The botanical supplement market, representing a substantial portion of the $177 billion global dietary supplement industry, faces a fundamental quality crisis that undermines consumer trust, clinical reproducibility, and public health. Despite current Good Manufacturing Practice (cGMP) regulations under 21 CFR Part 111 requiring dietary supplements to meet specifications for identity, purity, strength, and composition, a substantial proportion of products fail to deliver verifiable therapeutic value. [1][2]

Global authentication studies reveal that 27% of herbal products are adulterated, with specific botanicals showing even higher rates: 56% of ginkgo samples contained adulterants, 42% of black cohosh products were compromised, and 37% of Tongkat Ali products were found to be adulterated using DNA barcoding validated by HPLC analysis. These figures represent not merely economic fraud but a systemic failure of quality assurance that results in an estimated 23,000 emergency department visits annually in the United States attributed to dietary supplements. [3][4][5][6][7][8]

This white paper examines three critical deficiencies in current industry practices: (1) the inadequacy of botanical identification testing alone, (2) the unverifiable and frequently fraudulent nature of ratio extracts, and (3) the absence of standardization to pharmacologically active bioactive compounds. Using Tongkat Ali (Eurycoma longifolia) as a detailed case study, where Nootropics Depot has tested hundreds of samples over the better part of a decade, this document presents evidence-based recommendations for mandatory bioactive standardization as the only scientifically defensible approach to ensuring product quality, clinical validity, and consumer protection.


The Limitation of Identification: Why DNA Testing is Not Enough

Limitations of Botanical Authentication Methods

Current industry practice relies heavily on species identification through UV-VIS, DNA barcoding, microscopic examination, or macroscopic authentication. More enhanced identification methods using high performance thin layer chromatography (HP-TLC) have started to become more prevalent in recent years, through the efforts of companies like CAMAG. While these methods serve an important role in raw material verification, they are fundamentally insufficient for finished products without further orthogonal testing. This is particularly true for botanical extracts, which constitute the majority of commercial supplements.

Critical Limitation #1: DNA Degradation in Processed Materials

DNA barcoding requires relatively long gene sequences (500–1,000 base pairs) to function accurately. However, extraction processes involving heat, solvents, or chemical treatment fragment DNA into short pieces, rendering standard barcoding methods ineffective. Studies examining finished botanical dietary supplements have consistently found that “DNA in botanical dietary supplements containing extracts is of relatively poor quality, or absent altogether”. [9][10][11]

The 2015 controversy involving the New York Attorney General’s investigation into herbal supplements illustrates this limitation. While the investigation concluded that tested products lacked botanical material, subsequent expert analysis revealed that “the claim by the NY AG’s office that the tested products were devoid of botanical material was based on a misuse of technologies that led to misinterpretation of test results”. The absence of detectable DNA does not indicate whether a botanical product originated from a plant, “because the DNA can be removed while retaining the phytochemicals from the plant source”. [12][9]

Critical Limitation #2: Identification Does Not Equal Efficacy

Even when botanical identity is successfully confirmed, this provides no information about therapeutic value. Just because a supplement is proven to be Eurycoma longifolia or Hericium erinaceus does not mean it will give the effects that consumers expect, or that they read about in published research. Dietary supplements need to be more than just the correct species. They need to actually contain the bioactive compounds that lead to their expected effects.

This is because the plant itself is not responsible for the pharmacodynamic properties of the supplement. What is responsible are the specific compounds inside the plant or fungus, and if those compounds are not present in the supplement, it will not result in the benefits consumers are looking for. This disconnect between botanical authentication and pharmacological activity represents a fundamental flaw in current quality control paradigms. Confirming that a product contains Panax ginseng DNA or matches the HP‑TLC fingerprint reveals nothing about ginsenoside content, bioavailability, or clinical effectiveness.

Illustrative HP‑TLC and UPLC Data

HP‑TLC plate of a Tongkat Ali product that passed ID testing, but only contained 0.075% eurycomanone

The far right lane is the sample with 0.075% eurycomanone, and the far left lane is the botanical reference material. The two center lanes are Nootropics Depot 2% eurycomanone and 10% eurycomanone extracts.

This test indicates the sample tested is a non‑extracted Tongkat Ali root powder on the lower end of expected native eurycomanone concentration.

HPTLC plate comparing eurycomanone tongkat ali extracts, showing distinct fluorescent bands for BRM, reference, and SI samples.

HP‑TLC plate of a Tongkat Ali product that failed ID testing, and contained ZERO eurycomanone

The far right lane is the sample with 0% eurycomanone, and the far left lane is the botanical reference material. The two center lanes are Nootropics Depot 2% eurycomanone and 10% eurycomanone extracts.

This test indicates the sample tested is not Tongkat Ali at all, and further UPLC testing showed it contained none of the expected quassinoids.

HPTLC plate of tongkat ali eurycomanone identity testing, comparing BRM, reference extracts

Tongkat Ali: Where Identification Testing Fails

The inadequacy of identification testing becomes starkly evident in the Tongkat Ali market. Published research using DNA barcoding validated by HPLC analysis found that 37% of tested Tongkat Ali herbal medicinal products were adulterated. More critically, the researchers documented situations “in which a species which was identified as authentic was found not to contain the expected chemical compound.” Products that passed species identification but failed chemical verification. [6][7][15]

 

Infographic illustrating the blind spot of testing with an iceberg analogy.

This finding reveals the fatal flaw in identification‑only approaches: a product can be authentically derived from Tongkat Ali root while containing zero therapeutic value. In Nootropics Depot’s own testing over the years, internal lab data show that the percentages of products that are adulterated in some manner are even higher than 37% in many cases. Some sections of the supplement market are nearly 100% adulterated, as seen in testing on turkesterone products from a few years ago, in which every single turkesterone product on the market did not even contain turkesterone, nor were they even the species of plant they claimed to be.

For Tongkat specifically, the incidents of retail products not containing Eurycoma longifolia at all are relatively low, but that only tells part of the story. When eurycomanone content is tested is where the real picture starts to form. Initial rounds of testing of Tongkat products on the market found that most contained little to no eurycomanone, even as most tested positive for Eurycoma longifolia DNA and HP‑TLC fingerprints. Identity testing alone would not have shown the real state of the quality of the Tongkat Ali products on the market.

UPLC chromatogram of a Tongkat Ali sample that passed ID, but contained very little eurycomanone

This sample passed testing for identity, confirming that it is Eurycoma longifolia. However, further UPLC testing showed almost zero eurycomanone. This product claimed to contain 240 mg of Tongkat Ali extract with no fillers or excipients. However, the lab found that each capsule contained 386 mg of powder, meaning it was either overfilled by a significant margin, or contained undisclosed fillers and/or carriers. Based on the 240 mg claim, the 0.03 mg per capsule means there was 0.0125% eurycomanone; based on 386 mg actual mass, there was 0.0078% eurycomanone. Both of these are well below the native concentration of eurycomanone in dried non‑extracted root, and the lack of distinct peaks for other quassinoids indicates that this product contains spent marc.

UPLC chromatogram report for tongkat ali sample SSF-2852.4 showing eurycomanone peak at 5.715 minutes with 0.03 mg per capsule result.

The Ratio Extract Deception: Fabricated Numbers and Spent Marc Fraud

The Tongkat Ali Scandal: A Case Study in Systematic Deception

No botanical ingredient better exemplifies the systematic deception of ratio extracts than Tongkat Ali (Eurycoma longifolia). This Southeast Asian root, valued for its testosterone‑supporting and adaptogenic properties attributed to quassinoid compounds like eurycomanone, has become ground zero for one of the industry’s most egregious fraud schemes. [16]

Infographic debunking inflated botanical claims with cost and weight comparisons.

The Fabrication of 100:1 and 200:1 Ratios

The U.S. market is flooded with Tongkat Ali products labeled as “100:1 extract” or “200:1 extract” ratios that suggest extraordinary potency and concentration. Laboratory testing and direct admissions from suppliers show that these numbers are entirely fabricated marketing constructs with no basis in actual extraction methodology.

To get 100kg of a real 100:1 extract, you would need to discard 99kg of plant material for every 1kg of finished extract. For one, the economics of this make these crazy extract ratios not just uncommon in reality, but unheard of. Furthermore, the higher you go in extract ratio, the more the finished product clumps and requires carriers to keep them stable. However, none of these brands claiming insane ratios like 100:1 or 200:1 list carriers.

Suppliers have openly admitted that they assign these inflated ratios because “that’s what US supplement companies want to see”, not because the products represent genuine 100:1 or 200:1 concentrations. Our laboratory has tested hundreds of Tongkat Ali samples over many years, and the data reveal the scope of this deception:

  • Many products labeled “100:1” or “200:1” are not extracts at all; they are simply non‑extracted Tongkat Ali root powder.
  • The limited number of products that are actual extracts typically represent modest 2:1 to 4:1 extractions at best.
  • Eurycomanone content in these fraudulent products often measures 0.1% or less, barely above or even below the native concentration found in non‑extracted root.

As industry analysts have concluded, “any respectable Medical Herbalist or Phytochemist would not mention any extraction ratio greater than 30:1 or 33:1 at the highest” for Tongkat Ali. The prevalence of 100:1 and 200:1 claims represents pure fabrication designed to exploit consumer ignorance. [20]

Understanding Native Eurycomanone Baselines

Through extensive testing of raw Tongkat Ali root material, we have established that native eurycomanone concentration in non‑extracted, dried Tongkat Ali root consistently measures 0.08% to 0.18%. All non‑extracted root material tested over the years falls within this range.

This baseline is critical for detecting fraud. Any product claiming to be an extract that contains eurycomanone levels at or below this native range is either:

  1. Not an extract at all (simply ground root powder).
  2. Spent marc from which bioactives have been previously extracted.
  3. Heavily diluted extract mixed with non‑extracted material or excipients.

A genuine extract, even a modest 2:1 or 4:1 concentration, should show eurycomanone levels meaningfully above the 0.08–0.18% baseline if the extraction was done properly. Products claiming 100:1 or 200:1 extraction with eurycomanone content of 0.15% or 0.2% are mathematically impossible and represent obvious fraud.

That’s not even the worst of it. Most of the products on the market that claim to be 100:1 or 200:1 contain less than 0.001% eurycomanone, or none at all in many cases. These results are not just coming from small no-name brands on Amazon. We are finding these horribly low levels in large and seemingly reputable brands as well.

The Mathematical Ambiguity of Ratio Specifications

A plant‑to‑extract ratio indicates only the quantity of starting material used to produce a unit of extract. For example, a 5:1 ratio means 5 kilograms of plant material were processed to yield 1 kilogram of extract. However, this ratio provides no information about: [21]

  • The bioactive compound content of the starting material.
  • The efficiency of the extraction process.
  • The concentration of therapeutically relevant constituents in the final product.
  • The presence or absence of excipients or fillers.

Peer‑reviewed analysis notes that “Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the make‑up of final extracts, such as the quality of the raw starting material, extraction solvent(s) used, duration and temperature of extraction, and percentage and type of excipients present”. [21]

The situation becomes more problematic when excipients are added. If two parts of native extract are produced from eight parts of starting material (a genuine 4:1 ratio), and then a 50% maltodextrin carrier is added, the actual ratio becomes 2:1. However, most brands continue to label this as a 4:1 extract. Without disclosure of excipient percentages, consumers and healthcare practitioners cannot determine actual active ingredient levels. [21]


The Spent Marc Scheme: Selling Extracted Waste as Premium Product

The Most Insidious Form of Botanical Fraud

Beyond fabricated ratios lies an even more sophisticated adulteration pattern: the systematic resale of spent marc, or the depleted plant material remaining after bioactive compounds have been extracted. In the Tongkat Ali market, this scheme operates with remarkable efficiency:

Diagram illustrating the

 

  • Step 1: Primary Extraction. Manufacturers extract Tongkat Ali root to obtain eurycomanone and other valuable quassinoids using ethanol or other organic solvents.
  • Step 2: Premium Sale. The bioactive‑rich extract is sold at premium prices to manufacturers who conduct rigorous testing, such as Nootropics Depot and other quality‑focused brands that assay for eurycomanone content using validated HPLC/UPLC methods.
  • Step 3: Spent Marc Resale. The leftover plant material, now depleted of therapeutic compounds, is sold to brands that perform no assay testing or only basic identification tests. These brands receive material that is technically authentic Tongkat Ali but functionally worthless. These products are even sold as the extract ratios that were used to make the extracts sold to other brands, but with flipped ratios. This means that the spent marc from a real 10:1 extract will be labeled as a 10:1 extract, then sold to brands that do not do proper bioactive testing.
  • Step 4: Adulteration Evolution. Some suppliers now mix non-extracted root powder back into the spent marc to further deceive testing methods, creating products that show strong identification test results while remaining therapeutically inferior. This makes the HP-TLC fingerprint signals stronger, tricking that ID method, and adds more DNA into the end product, tricking the DNA identification methods.

The Smoking Gun: Sub‑Native Eurycomanone Levels.

The definitive evidence of spent marc fraud is eurycomanone content below the 0.08–0.18% native baseline. Numerous tested products show eurycomanone concentrations of 0.001% to 0.04%, or similarly depressed levels. Non‑extracted root material consistently tests at 0.08–0.18% eurycomanone, so any product testing below this range has been depleted of bioactives through extraction, definitively proving it is spent marc. This is the “smoking gun” that identification testing cannot detect.

Why This Scheme is Particularly Devious

Spent marc fraud succeeds because the depleted material remains authentically derived from Tongkat Ali root. It will pass multiple layers of quality control that do not measure bioactive content:

  • DNA Barcoding: ✓ Passes (Tongkat Ali DNA still present)
  • HP‑TLC Fingerprinting: ✓ Passes (shows appropriate bands for Tongkat Ali, though potentially fainter)
  • Microscopic Authentication: ✓ Passes (cellular structures remain intact)
  • Certificate of Analysis: ✓ Passes (if supplier only tests for identity, not bioactives)

The critical difference is invisible to these methods: eurycomanone levels in spent marc products are lower than those found in non‑extracted root, which is definitive proof that bioactive compounds have been stripped away.

When suppliers mix non‑extracted root back into spent marc, they create products that pass identification testing with flying colors but still show depressed eurycomanone content, demonstrating that the bulk of the material has been previously extracted. This represents a “perfect fraud”: spent marc looks authentic, tests as authentic, but delivers no therapeutic benefit. Only bioactive quantification reveals the deception.

Chromatogram of non‑extracted dried Tongkat Ali root material

Graph showing anti-burst chromatography results over time with labeled peaks.

The Wider Context: Spent Marc Fraud Across the Botanical Industry

A Systematic Problem Documented by Leading Experts

The Tongkat Ali case exemplifies a fraud pattern documented across the botanical supplement industry. A comprehensive 2024 report published in HerbalGram by the Botanical Adulterants Prevention Program (BAPP) exposed the widespread practice of excessive dilution and spent marc resale. [22][23]

The report identifies two primary fraud schemes:

Scheme 1: Excessive Dilution with Undeclared Excipients

Suppliers dilute native plant extracts with undisclosed amounts of carriers (typically maltodextrin) while providing ambiguous or misleading plant-to-extract ratios. Examples documented include:

  • Valerian extract containing 0.25% actual extract and 99.75% maltodextrin. [22]
  • Lady’s mantle extract diluted 80‑fold beyond its claimed 5:1 ratio, yielding an actual ratio of 0.06:1. [22]
  • Multiple elderberry, ginkgo, and black cohosh extracts showing minimal or absent characteristic compounds. [22]

Scheme 2: Spent Marc Resale

“Whole herbs are extracted to obtain specific fractions or compounds that are considered to be therapeutically beneficial and are provided to select markets. The marc (leftover or spent biomass) may then be re‑sold without disclosure that it is pre‑extracted material.” [22]

Industry experts compare this to coffee grounds: “That first cup is great, but then someone passes off the grounds as full potency. The coffee genes may still be in there, but it’s extracted waste product.” [24]

Flora Research Laboratories has identified spent marc in saw palmetto and valerian products that were water extracts mainly composed of sugars and devoid of any of the characteristic saw palmetto fatty acids or typical valerenic acids. While these products technically pass identity tests, they have no known pharmacological or clinical research supporting health benefits. [22]

The Supply Chain Deception: Multiple Tiers

  • Tier 1: Premium extracts sold to quality‑conscious supplement manufacturers who conduct bioactive testing.
  • Tier 2: Spent material re‑extracted with water and sold as “botanical extract” to manufacturers who rely solely on identification testing.
  • Tier 3: Spent marc mixed with non‑extracted material or excessive excipients to pass basic chromatography tests.

Contract analytical laboratories report an alarming trend. BotaniCERT's analysis of 1,028 botanical extracts between 2017–2019 found that 11% were classified as “empty” or devoid of any constituents characteristic of the labeled botanical. Zero crude botanical materials showed this problem, confirming that fraud targets the extract market specifically. [22]


The Bioactive Imperative: Why Only Compound‑Specific Testing Reveals the Truth

The Hierarchy of Testing Methods

The Tongkat Ali spent marc fraud demonstrates why bioactive compound standardization is not optional. It is the only method capable of detecting sophisticated adulteration schemes. The hierarchy of testing methods shows what each can and cannot detect:

DNA Barcoding

  • ✓ Confirms species identity

  • ✗ Cannot detect spent marc (still contains Tongkat Ali DNA)

  • ✗ Cannot detect dilution with excessive excipients

  • ✗ Cannot measure absence of therapeutic compounds

  • ✗ Cannot quantify extraction efficiency or bioactive concentration

  • ✗ Ineffective for processed extracts due to DNA degradation

HP‑TLC Fingerprinting

  • ✓ Shows chemical profile pattern for identification

  • ✓ Can quantify eurycomanone when paired with CAMAG quantification module

  • ✗ Less accurate than UPLC for precise quantification

  • ✗ Cannot reliably detect spent marc if characteristic bands remain visible (even if faint)

  • ✗ Subjective interpretation of band intensity without quantification add-on

UPLC‑UV or HPLC‑UV

  • ✓ Reveals precise eurycomanone and quassinoid content

  • ✓ Confirms whether extraction has occurred and at what efficiency

  • ✓ Detects spent marc fraud (sub-native bioactive levels)

  • ✓ Ensures product-to-product consistency

  • ✓ Predicts actual therapeutic potential

  • ✓ Validates bioactive concentration claims

  • ✓ Gold standard for bioactive quantification


Tongkat Ali: The Eurycomanone Standard and Quassinoid Profile

Eurycomanone is the most extensively studied bioactive compound in Tongkat Ali, with documented effects on testosterone production, stress response, and athletic performance. Through years of comprehensive testing using validated UPLC‑UV methods, Nootropics Depot has established rigorous quality benchmarks for Tongkat Ali.

Native baseline (dried non‑extracted root)

  • Eurycomanone: 0.08–0.18%.
  • Other quassinoids (combined): approximately equal to eurycomanone content.
  • Total quassinoids: approximately 0.16–0.36%.

Quality extract specifications

  • Eurycomanone: minimum 0.4% for acceptable extracts; 1-10% for premium standardized extracts
  • Other quassinoids: roughly equivalent percentage to eurycomanone (e.g., in a 0.8% eurycomanone product, expect ~0.8–1.0% other quassinoids)
  • Eurycomanone is always the dominant quassinoid, with others collectively matching its concentration

The Reality of Market Products

The European Food Safety Authority (EFSA), in evaluating Tongkat Ali for novel food approval, referenced extracts standardized to 0.8–1.5% eurycomanone as high‑quality materials. However, most market products fall well below this specification. [26][27]

Even more troubling, the most clinically studied Tongkat Ali extracts, LJ‑100 and Physta, claim standardization to 0.8–1.5% eurycomanone in marketing materials, or even up to 3% in some places such as Akarali’s site. Extensive testing of numerous batches from multiple brands using these proprietary extracts consistently shows actual eurycomanone content, never reaching the claimed upper specification: [26][27]

  • Actual eurycomanone content: 0.4-0.8%

  • Never reaches the claimed 1.5%-3% upper specification claims

  • Typically clusters around 0.5-0.6% in most batches

This represents a significant disconnect between claimed standardization and actual measured content. Even the extracts backed by clinical research, the gold standard materials that other products attempt to emulate, fail to consistently meet their own published specifications.

The Eurypeptide Myth: Standardization to Fictitious Compounds

Beyond spent marc and fabricated ratios lies another insidious practice: standardization to compounds that are either unvalidated, irrelevant to therapeutic activity, or entirely fictitious. The "eurypeptide" standardization claim exemplifies this problem.

The Origin of the Eurypeptide Myth

Multiple brands market Tongkat Ali products standardized to "eurypeptides" or "glycoproteins," claiming these represent important bioactive compounds. This claim originates from a single paper that used a basic Lowry's total protein assay. This is an outdated colorimetric method that measures total protein content without any peptide-specific validation, and is subject to many factors that can both understate and overstate results from reality. This includes many matrix interferences from the sample being tested, even substances commonly present in samples, like potassium, magnesium, ammonium, and carbohydrates.

The researchers measured total protein, then labeled that figure as "eurypeptides" without:
    • Isolating or characterizing any specific peptides
    • Validating that peptides (rather than other proteins or amino acids) accounted for the measurement
    • Demonstrating bioactivity of the measured fraction
    • Addressing matrix interferences in the Lowry assay, which is known to produce artifacts

Why Eurypeptide Standardization is Scientifically Invalid

The scientific evidence is unambiguous: quassinoids, particularly eurycomanone, are the primary bioactive compounds in Tongkat Ali, not peptides. Multiple lines of evidence refute peptide bioactivity:[16][25]
    1. Oral bioavailability: Even if peptides were present, they would not absorb intact through oral administration due to gastric acid and digestive enzyme degradation
    2. Processing incompatibility: LJ-100 and Physta use hot water extraction processes that would denature any peptides present
    3. Mechanism of action: Documented testosterone, cortisol, and performance effects are attributed to quassinoid activity, not peptide signaling
    4. Analytical artifacts: The Lowry method is subject to interferences from phenolic compounds, nucleic acids, and other matrix components

At best, "eurypeptide" measurements represent total protein content in the plant material, which is a nutritionally irrelevant specification. At worst, they represent analytical artifacts from an inappropriate methodology . In either case, they provide zero information about therapeutic potency.

The Broader Problem: Made‑Up Standardization Terms

The eurypeptide example illustrates a pervasive industry problem: standardization to marketing terms rather than validated bioactive compounds. Other examples include:

  • “Proprietary polyphenol blends” without specification of individual compounds.
  • “Bioactive fractions” with no chemical characterization.
  • “Phytocomplex ratios” that are unmeasurable.
  • “Active principles” without identification of those principles.
  • Trademarked names for bioactives that are not fully elucidated or validated (e.g., Saffromotivines, Fenuside, Lepticrosalides).

These terms sound scientific while providing no actionable information about product quality or therapeutic value. They allow manufacturers to claim standardization without the expense and accountability of actual bioactive quantification and can create standards that no other brand can use because the term itself is trademarked.

The Gold Standard: Evidence‑Based Bioactive Standardization

Legitimate standardization must follow the scientific evidence and clinical research:

  • Tongkat Ali: Eurycomanone and total quassinoids by HPLC/UPLC‑UV. [28]
  • Ginkgo biloba: Bilobalide, flavone glycosides, and terpene lactones by HPLC/UPLC‑UV.
  • Milk thistle: Silymarin (with silibinin, silychristin, silydianin specified) by HPLC/UPLC‑UV.
  • Ashwagandha: Withanolides by HPLC/UPLC‑UV.
  • Turmeric: Curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) by HPLC/UPLC‑UV or spectrophotometry.
  • Bacopa: Bacopasides by HPLC/UPLC‑UV.

These specifications are based on:

  • Compounds with demonstrated pharmacological activity
  • Methods validated in peer-reviewed literature
  • Specifications used in clinical efficacy studies
  • Analytical techniques that can be independently verified

Standardization to anything else, whether eurypeptides, proprietary fractions, or undefined "bioactive complexes,” represents either scientific ignorance or deliberate obfuscation.


The Trust Crisis: When Even Clinical Extracts Don’t Meet Specifications

The Physta Specification Problem

The disconnect between claimed and actual eurycomanone content in Physta extracts represents a crisis of credibility that extends beyond individual products. These proprietary extracts are:

  • The most clinically studied Tongkat Ali materials on the market
  • Referenced in multiple peer-reviewed publications
  • Used as benchmarks by other manufacturers attempting to formulate evidence-based products
  • Marketed with explicit standardization claims to 0.8-1.5% eurycomanone, or 3% in some cases

Yet our testing of batches shows actual eurycomanone content of 0.4-0.8%—never reaching the claimed 1.5% (or 3% in the case of Akarali) upper specification and frequently falling significantly below 0.8%.

UPLC chromatogram of a batch of Akarali Eury-Prep 200, that contains Physta

UPLC chromatogram of a batch of Akarali Eury-Prep 200, that contains Physta

Implications for the Industry

This finding has profound implications:
    1. Clinical research validity: Studies conducted with batches claiming 1.5% eurycomanone that actually contained 0.6% used half the presumed active compound dose
    2. Dose calculations: Healthcare practitioners recommending products based on published specifications are unknowingly under-dosing patients
    3. Competitive claims: Manufacturers using these extracts and claiming "clinically studied dosages" are making representations that may not match actual bioactive delivery
    4. Consumer deception: End users paying premium prices for "standardized" extracts receive less bioactive content than claimed

If even the most reputable, clinically validated extracts fail to meet their own specifications, what confidence can consumers have in the broader market?

The Akarali Overstating Problem

Brand-level misrepresentation compounds the issue. Akarali, a prominent Tongkat Ali brand, consistently overstates eurycomanone concentrations on their website and marketing materials. This pattern of specification inflation contributes to:

  • Unrealistic consumer expectations about what constitutes quality
  • Pressure on honest manufacturers to either match inflated claims or lose market share
  • Erosion of standardization credibility when testing reveals discrepancies
  • Regulatory scrutiny of the entire category

When a brand that purports itself to be an authority in the space makes exaggerated claims, it damages industry-wide trust and makes fact-based quality communication more difficult.


Regulatory Framework and Industry Obligations

Current Good Manufacturing Practices: The Legal Requirement

Federal regulations under 21 CFR Part 111 explicitly require dietary supplement manufacturers to establish specifications for "the identity, purity, strength, and composition" of both components and finished products. The regulation defines quality as ensuring products “consistently meet the established specifications" and "prevent adulteration".[2][29][1]

Critically, the FDA has clarified that "the amount of labeled extract does not include any flow agents, anticaking agents, antistatic agents, lubricants, or whatever else companies may add to an extract to improve the ability to process it. And it certainly wouldn't include any fillers used to adjust the plant-to-extract ratio". This interpretation contradicts current industry practices that label diluted extracts as if excipients were part of the botanical content.[22]

Despite these clear requirements, FDA inspection data reveals systematic non-compliance. The most common observations in 2023-2024 include:

  1. Failure to establish product specifications for identity, purity, strength, and composition[30][31]
  2. Inadequate testing of raw materials for identity verification[31]
  3. Missing component specifications for purity, strength, and composition[31]
  4. Deficient master manufacturing records[30]

These violations directly contribute to the widespread adulteration documented in authentication studies and enable spent marc fraud schemes.

The Legal Definition of Strength

Under 21 CFR Part 111, "strength" is defined in relation to the dietary ingredient itself, not merely its presence or absence. For botanical extracts, strength specifications must address:

  • Concentration of bioactive constituents: Eurycomanone percentage in Tongkat Ali, ginsenosides in ginseng, curcuminoids in turmeric, etc.
  • Batch consistency: Demonstrable reproducibility of bioactive levels
  • Manufacturing controls: Process validation ensuring consistent extraction efficiency

A product that passes identity testing but contains spent marc or excessive dilution fails the "strength" requirement. Similarly, a fabricated 100:1 or 200:1 ratio claim without corresponding bioactive content represents a violation of labeling regulations under 21 CFR 101.36. Products claiming standardization to 1.5% eurycomanone that actually contain 0.6% are misbranded under federal law. This applies equally to raw material suppliers and finished product manufacturers.


The Path Forward: Mandatory Bioactive Standardization

Industry Action Items

The botanical supplement industry must transition from identification-based quality control to bioactive-compound standardization. This requires immediate action across five domains:

1. Abandon Ratio Extract Claims Without Bioactive Verification

Plant-to-extract ratios must either be disclosed accurately with supporting analytical data or eliminated entirely from marketing claims. When ratio specifications are used, labels should declare:

  • Native extract ratio (genuine Plant-to-Extract Ratio) separately from total ratio including excipients
  • Percentage of actual extract versus carriers and flow agents
  • Validated bioactive compound content with analytical method citation
  • Batch-specific certificate of analysis available upon request

For Tongkat Ali specifically: Any product claiming 100:1 or 200:1 extraction must provide UPLC evidence of eurycomanone concentration meaningfully above the 0.08-0.18% native baseline. Products claiming high ratios with eurycomanone at or below native levels are prima facie fraudulent.

2. Implement Compound‑Specific Testing for Every Batch

Every batch of botanical extract must be tested for the unique bioactive compounds responsible for therapeutic effects using validated methods:

  • Tongkat Ali: Eurycomanone and quassinoid profile by HPLC/UPLC‑UV or HP‑TLC with CAMAG quantification.
  • Ginkgo biloba: Flavone glycosides and terpene lactones.
  • Milk thistle: Silymarin components.
  • Ashwagandha: Withanolides.
  • Turmeric: Curcuminoids.

Specifications must be based on clinical research standards and pharmacopeial monographs, not arbitrarily selected markers or fictitious terms like “eurypeptides”.

3. Demand Supply Chain Transparency

Manufacturers must require from suppliers:

  • Certificates of Analysis with bioactive quantification, not just identification testing
  • Disclosure of extraction methodology: solvents, temperatures, duration, and yield
  • Flow charts of the extraction process showing each step
  • Confirmation that materials are not spent marc or post-extraction waste
  • Batch-to-batch consistency data demonstrating process control
  • Traceability to geographic origin and harvest practices

For Tongkat Ali, manufacturers should explicitly ask suppliers: "Has this material been extracted, and how?" and "What is the eurycomanone content measured by HPLC/UPLC?" Any hesitation or inability to provide validated analytical data should disqualify the supplier. Relying on Certificates of Analysis that only confirm species identity through DNA, UV-VIS, or even HP-TLC, enables spent marc fraud. This is only step one in the process. Brands cannot trust supplier documentation alone. This supplier documentation needs to be used as a starting point for a brand’s own internal specification sheets, then to determine what independent verification needs to happen to ensure the batch meets that spec.

4. Implement Third‑Party Verification

Independent testing through ISO accredited laboratories is no longer just a nice-to-have. It is a must for every batch of every product from every supplier. Third-party verification eliminates conflicts of interest inherent in supplier-provided testing and ensures that each batch meets its specifications and label claims. Moreover, this testing needs to be done by ISO/IEC 17025:2017 accredited labs that have shown proficiency in the specific testing they are undertaking. This includes ensuring that the lab’s ISO scope contains validated methods and proficiency in the exact methodologies being used to test that specific batch of product. A lab that is ISO accredited, but only has microbial testing on their scope, should not be used to assay for unique bioactives in plant material. The lab needs to be proficient in the methodologies needed to accomplish the testing being ordered. If you order an assay for eurycomanone via UPLC from a lab that doesn’t have any UPLC methods on their scope, you are not using an appropriate lab for that test.

5. Educate Consumers and Healthcare Practitioners

The industry must invest in consumer education about quality indicators:

  • Ratio claims are meaningless without bioactive data: A 200:1 Tongkat Ali extract with 0.03% eurycomanone is inferior to non-extracted root powder at 0.15%
  • Look for standardization statements based on science: "Standardized to 0.8% eurycomanone by UPLC" provides actionable information; "100:1 extract" or "standardized to eurypeptides" does not
  • Understand native baselines: Tongkat Ali eurycomanone should be meaningfully above 0.08% - 0.18% to represent genuine extraction
  • Third-party testing matters: Ensure these labs are ISO accredited for the methods being used
A 5-step action plan for botanical product integrity.

Economic and Public Health Implications

The True Cost of Adulteration

The failure to implement bioactive standardization carries consequences that extend far beyond economic fraud:

Consumer Harm

Beyond the 23,000 annual emergency department visits attributed to dietary supplements, adulterated products expose consumers to:[8]

  • Ineffective therapy for serious health conditions: Consumers relying on botanical support for testosterone production, stress management, or other indications receive no therapeutic benefit from spent marc or diluted products
  • Wasted healthcare expenditures: Billions spent annually on non-functional products
  • Pharmaceutical contamination: 746 brands identified by FDA between 2007-2016 containing undeclared drugs[8]
  • Allergenic or toxic adulterants: Substitution of incorrect plant species or addition of synthetic compounds[35][36]

Economic Fraud and Market Distortion

Spent marc and fabricated ratio claims create unfair competitive advantage for low-quality manufacturers:

  • Price compression: Companies selling spent marc or non-extracted powder labeled as "100:1 extract" at premium prices undercut manufacturers using genuine standardized extracts
  • Consumer confusion: Proliferation of 100:1 and 200:1 Tongkat Ali claims creates expectation that these ratios are legitimate
  • Specification inflation: Brands like Akarali overstating eurycomanone content force honest manufacturers to either match false claims or lose market share
  • Regulatory arbitrage: Companies that don't test for bioactives have lower quality control costs, gaining competitive advantage through non-compliance

With the global botanical supplement market exceeding $50 billion annually, fraudulent revenue from spent marc, excessive dilution, and fabricated ratios likely represents several billion dollars. This is money extracted from consumers who believe they are purchasing therapeutic products.

Clinical Research Validity

Studies conducted with non-standardized or adulterated materials produce irreproducible results:

  • Dosing inconsistency: If batches used in one clinical trial contained 0.3% eurycomanone, but were assumed to contain 1.5%, efficacy assumptions about products will be wrong
  • Negative studies may reflect poor material quality, not lack of efficacy
  • Positive results cannot be replicated if commercial products don't match research material specifications
  • Meta-analyses become impossible when included studies used heterogeneous materials with different bioactive concentrations
  • Research funding is wasted on poorly characterized interventions

The scientific literature on botanical medicine loses credibility when commercially available products bear no resemblance to materials tested in clinical trials, and when even the clinical materials don't meet their own specifications. Moreover, it is the responsibility of the authors of studies to verify standardization claims before conducting their experiments. Manufacturer claims cannot be used as evidence of bioactive concentration when scientific research is conducted.


Conclusion: The Industry’s Choice

The botanical supplement industry stands at a critical juncture. Through years of rigorous testing involving hundreds of Tongkat Ali samples and validated UPLC methods, we have documented systematic fraud that extends from raw material suppliers through finished product manufacturers. The evidence is clear and compelling:

  • Identification testing cannot ensure quality: DNA barcoding and HP-TLC confirm species but provide no information about therapeutic value
  • Ratio extracts are frequently fabricated: some suppliers openly admit to inventing 100:1 and 200:1 Tongkat Ali ratios "because that's what US supplement companies want to see"
  • Spent marc schemes systematically deceive consumers: Suppliers extract eurycomanone for premium markets, then resell depleted waste material to brands that don't conduct assay testing
  • Sub-native eurycomanone levels indicates prior extraction: Products testing below the 0.08-0.18% baseline have been stripped of bioactives
  • Fraudulent standardization terms proliferate: "Eurypeptides" and similar made-up markers provide zero therapeutic information
  • Only bioactive standardization detects fraud: HPLC/UPLC quantification of eurycomanone reveals spent marc, dilution, and specification misrepresentation

This is not just poor quality control. It is systematic and intentional fraud that harms consumers, damages industry credibility, and violates federal law under 21 CFR Part 111.

The Solution is Non‑Negotiable

Standardization to unique, pharmacologically active bioactive compounds, validated through sophisticated analytical chemistry and supported by clinical evidence, is the only approach that can deliver on the industry's promise to consumers.

For Tongkat Ali, this means:

  • Abandoning meaningless 100:1 and 200:1 ratio claims
  • Requiring minimum 0.4% eurycomanone by UPLC-UV (acceptable quality) or 2%+ (premium quality)
  • Testing every batch against the 0.08-0.18% native baseline to detect spent marc
  • Profiling total quassinoids to ensure comprehensive bioactive presence
  • Demanding supply chain transparency about extraction status
  • Rejecting "eurypeptide" and other fictitious standardization terms
  • Holding clinical extract manufacturers accountable to their specifications

For the broader botanical industry, this means:

  • Implementing compound-specific standardization based on clinical research
  • Rejecting suppliers who cannot provide UPLC or HPLC bioactive quantification
  • Supporting regulatory action to mandate disclosure and eliminate deceptive practices
  • Investing in third-party verification through independent laboratories
  • Educating consumers about the difference between identification and potency testing
  • Exposing fraud through transparent testing and public education

The Competitive Advantage of Quality

Companies that embrace bioactive standardization will establish market leadership through demonstrated quality, clinical validity, and consumer trust. Testing for eurycomanone by validated UPLC methods is not an unnecessary cost. It is the only testing that matters. It ensures products deliver the health benefits consumers expect and deserve.

Nootropics Depot and other quality-focused brands that have invested in comprehensive quassinoid profiling, validated analytical methods, and rigorous supply chain verification should not be outliers. This should be the minimum standard for ethical commerce in the supplement industry. The fact that it is 2025 and we are still having this conversation represents a systemic failure on the part of entrenched authorities in the supplement industry. It is much easier to make money by false claims and obfuscation than spending the money on ensuring proper science is done before products reach consumers. It’s up to the thought leaders in the space, like industry organization, testing labs, and certification companies, to force brands to take things seriously. We need to have difficult conversations now, so that we can force real positive change for consumer trust and safety.

Those that continue to rely on identification testing, unverifiable ratio claims, or fictitious standardization terms will face increasing scrutiny from regulators, practitioners, and an increasingly sophisticated consumer base. The market is evolving. Consumers are learning to ask: "What is the eurycomanone content measured by UPLC?" Healthcare practitioners are demanding standardization data before making recommendations. Regulatory agencies are documenting adulteration patterns. If we as an industry don’t come together and self-regulate, and hold the bad actors accountable, this space will face more legal and regulatory action that will undeniably damage the reputation of dietary supplements as a whole.

Brands Have A Choice

The choice facing the botanical supplement industry is binary: embrace bioactive standardization or perpetuate a fraud that will eventually destroy consumer confidence and invite regulatory intervention. The bioactive imperative is not aspirational. It is the minimum standard required for ethical commerce and regulatory compliance under 21 CFR Part 111. The future of the botanical supplement industry depends on our collective commitment to standardization based on the compounds that matter: eurycomanone in Tongkat Ali, ginsenosides in ginseng, silymarin in milk thistle, and withanolides in ashwagandha. These are the bioactives that deliver authentic health benefits. These are the compounds that define product quality. These are the specifications that separate therapeutic products from spent marc, diluted extracts, and fraudulent ratio claims. As we move forward in 2025, the industry must choose quality over deception, transparency over opacity, and science over marketing fiction. Our years of testing hundreds of Tongkat Ali samples have illuminated the problem with unprecedented clarity. Now comes the responsibility to implement solutions.

The spent marc must be called what it is: extracted waste. The 100:1 and 200:1 ratios must be called what they are: fabricated numbers. The eurypeptides must be called what they are: fictitious markers. And the products claiming standardization without UPLC verification must be called what they are: unverifiable and likely fraudulent. Only then can the botanical supplement industry fulfill its promise to consumers and earn the trust required for sustainable growth.


References

1. https://www.cdph.ca.gov/Programs/CEH/DFDCS/CDPH%20Document%20Library/FDB/FoodSafetyProgram/DietarySupplements/21CFRPart111.pdf

2. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/small-entity-compliance-guide-current-good-manufacturing-practice-manufacturing-packaging-labeling

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31. https://certified-laboratories.com/blog/detailing-the-top-five-21-cfr-111-compliance-issues-for-supplement-manufacturers/

32. https://www.scientificamerican.com/custom-media/setting-standards-for-supplements/

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This content is for informational purposes only and is not intended as medical advice. These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. Always consult a healthcare professional before starting any new supplement.