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Lessons learned Primary records, checked October 2026

Eight documented botanical failures each trace to a missing control, at identity, contamination, legal status or dose

What happened, what the primary record counted, what changed, and which control would have caught it, from a Brussels slimming clinic in 1993 to kratom actions in 2025 and 2026. Harms are described as published.

Status. EUTECNIQ was not involved in any case on this page. The controls named are proposals for a company that has no laboratory or products. Nothing here is medical advice.

Each harm was counted after people were exposed, under its own case definitionPrimary records
566cases with blood lead ≥ 3.5 µg/dL within 3 months of eating recalled cinnamon applesauce; 96% under age 6 (MMWR 2025)
18 of 39patients with aristolochia nephropathy who had prophylactic surgery had urothelial carcinoma (NEJM 2000)
24 of 29acute hepatitis cases of unknown cause in Hawaii, 2013, had used OxyELITE Pro (MMWR 2013)
≥ 800 mgEGCG a day from supplements raised liver enzymes in trials; mean intake from green tea is 90–300 mg (EFSA 2018)
MMWR 2025;74(14):239–244; Nortier et al., N Engl J Med 2000;342:1686–1692; MMWR 2013;62(40):817; EFSA Journal 2018;16(4):e05239.
Timeline

Thirty-three years of failures and responses: harm signals, investigations and the rules or rulings that followed

25 events in nine lanes, 1993 to 2026: select a dot, step through, or press PlayPrimary records
Sources are listed with each event. The time axis is stretched after 2010 (break mark), and close events in one lane are offset vertically. Import-alert dates are the current versions shown by FDA, not first issue dates.
Text version: all 25 events in date order
  1. 1993 Nine women with rapidly progressive kidney fibrosis after one slimming regimen Two index cases and seven more women under 50 in terminal or preterminal renal failure (1991–1992) had all followed the same slimming treatment at a Brussels clinic, which added two Chinese herbs in May 1990. Vanherweghem JL et al. Lancet 1993;341:387–391.
  2. October 25, 1994 DSHEA enacted The Dietary Supplement Health and Education Act created the notification duty for new dietary ingredients not marketed before October 15, 1994. Pub. L. 103-417; 21 U.S.C. 350b.
  3. June 1997 FDA proposes a dose limit for ephedrine alkaloids The proposal would have deemed a supplement adulterated at 8 mg or more of ephedrine alkaloids per serving; FDA withdrew that provision in April 2000. As described in 69 FR 6788 (Feb. 11, 2004).
  4. June 8, 2000 Urothelial carcinoma in 18 of 39 patients Aristolochia fangchi had replaced Stephania tetrandra in the slimming pills through a manufacturing error. Every tissue sample analyzed carried aristolochic acid–DNA adducts, and cumulative doses above 200 g carried higher risk. Nortier JL et al. N Engl J Med 2000;342:1686–1692.
  5. December 21, 2000 Causality review of 140 ephedra adverse-event reports 31% were judged definitely or probably related and 31% possibly related; 10 events were deaths and 13 caused permanent disability. Haller CA, Benowitz NL. N Engl J Med 2000;343:1833–1838.
  6. February 11, 2004 FDA declares ephedrine-alkaloid supplements adulterated The final rule found that they present an unreasonable risk of illness or injury; it took effect on April 12, 2004. 69 FR 6788 (Docket 1995N-0304).
  7. August 17, 2006 Appeals court upholds the ban at every dose Reversing a 2005 district ruling that had blocked enforcement at 10 mg a day or less, the Tenth Circuit held that FDA reasonably concluded "there is no recommended dose of EDS that does not present an unreasonable risk." Nutraceutical Corp. v. Von Eschenbach, 459 F.3d 1033 (10th Cir. 2006).
  8. June 25, 2007 Supplement cGMP rule requires identity testing 21 CFR Part 111 requires at least one appropriate test or examination to verify the identity of every dietary ingredient before use. 72 FR 34752; 21 CFR 111.75(a)(1)(i).
  9. April 2012 Warning letters to ten DMAA marketers Letters dated April 24, 2012 opened FDA's DMAA actions; its list grew to 18 firms by October 2017. FDA calls DMAA an amphetamine derivative that can raise blood pressure. FDA, DMAA in Products Marketed as Dietary Supplements (content current as of Feb. 22, 2023).
  10. 2013 DMAA formulations detained and destroyed FDA administratively detained OxyElite Pro and Jack3d after the distributor initially refused voluntary compliance; the products were destroyed. FDA DMAA page.
  11. October 11, 2013 Hepatitis cluster in Hawaii 29 cases of acute hepatitis of unknown cause, May 10 to October 3, 2013; 24 had used OxyELITE Pro. Eleven were hospitalized, two received liver transplants and one died. The product was recalled later in 2013. MMWR 2013;62(40):817; U.S. Department of Justice release, Mar. 13, 2019.
  12. February 2015 State attorney general halts sales after DNA tests The New York attorney general ordered four national retailers to stop selling certain herbal supplements after DNA barcoding failed to detect the labeled botanical in about 80% of products tested. As summarized in Wu DT et al. Sci Rep 2017;7:7792. The attorney general's release could not be retrieved for this page.
  13. 2016 Review: universal DNA barcodes cannot identify processed botanicals alone The authors do not recommend universal-primer DNA barcoding as the sole identification of processed plant material; they recommend combining specific DNA primers with chemical, microscopic and macroscopic methods. Parveen I et al. Planta Med 2016;82:1225–1235.
  14. March 13, 2019 Guilty pleas in the OxyELITE Pro and Jack3d case The distributor pleaded guilty to conspiracy involving mislabeled food. The indictment alleged that DMAA was imported with false certificates of analysis and sold as a natural plant extract. U.S. Department of Justice, Office of Public Affairs, Mar. 13, 2019.
  15. 2019 DMAA is not a dietary ingredient, a court affirms The Eleventh Circuit affirmed that "DMAA is not a dietary ingredient and is not generally recognized as safe"; the seized products were destroyed on November 12, 2020. FDA DMAA page.
  16. Current version, December 10, 2020 Import Alert 54-10 FDA detains, without physical examination, bulk and finished dietary supplements containing aristolochic acid. FDA Import Alert 54-10.
  17. February 2023 Ten turmeric liver-injury cases in a national network All ten were enrolled since 2011; five were hospitalized and one died. Seven carried HLA-B*35:01, an allele frequency of 0.450 against 0.056 to 0.069 in controls. Halegoua-DeMarzio D et al. Am J Med 2023;136:200–206.
  18. October 28, 2023 FDA alert on cinnamon applesauce pouches The distributor recalled the product the next day; the recall was expanded and reached 2,998,088 pouches. MMWR 2025;74(14):239–244.
  19. February 29, 2024 The source was lead chromate FDA reported that the lead and chromium in the recalled products and cinnamon came from lead chromate. MMWR 2025;74(14):239–244.
  20. January 7, 2025 Lead action levels for baby food Final guidance sets 10 ppb for fruits, most vegetables, mixtures, yogurts, custards and single-ingredient meats, and 20 ppb for single-ingredient root vegetables and dry infant cereals. 90 FR 1135; Docket FDA-2022-D-0278.
  21. April 24, 2025 566 cases in 44 States, DC and Puerto Rico 130 confirmed, 401 probable and 35 suspected; 96% were children under 6. Pouches from affected homes held 1.9 to 3.0 ppm lead. MMWR 2025;74(14):239–244.
  22. May 2025 Tianeptine: "not a dietary ingredient" FDA reports poison-center cases rising from 4 in 2013 to about 350 in 2024 and says it has issued import alerts to detain tianeptine shipments. FDA consumer update (content current as of May 9, 2025).
  23. July 29, 2025 FDA recommends scheduling 7-OH The recommendation targets concentrated 7-hydroxymitragynine products, "not natural kratom leaf products"; DEA rulemaking would follow. HHS press release, July 29, 2025.
  24. Current version, August 17, 2026 Import Alert 54-15 on kratom Supplements and bulk ingredients that are or contain Mitragyna speciosa are detained without physical examination as adulterated new dietary ingredients. FDA Import Alert 54-15.
  25. October 19, 2026 Final guidance on NDI identity and safety information Finalizes FDA's recommendations on identity, history of use and the safety narrative in a new dietary ingredient notification. 91 FR 66336; Docket FDA-2025-D-6501.

Five of the eight signals came from clinicians, a case registry, adverse-event reports or poison centers, after people had been exposed.

What was counted

The primary records count very different things, from 9 patients to 566 children

What each investigation counted, with its own definitionPrimary records
What each investigation counted: 566 lead cases, 140 ephedra reports, 39 patients in the aristolochia cohort, 29 hepatitis cases, 10 turmeric cases, 9 women in the first aristolochia reportCase or report definitionNumber counted (log scale)Lead and chromium, cinnamon applesauceCases with blood lead ≥ 3.5 µg/dL after eating a recalled product, 44 States, DC andPuerto RicoLead and chromium, cinnamon applesauce: 566566Ephedra alkaloidsAdverse-event reports to FDA reviewed for causation, June 1997 to March 1999Ephedra alkaloids: 140140Aristolochia (Belgium)Patients with end-stage nephropathy who had prophylactic surgery; 18 had urothelialcarcinomaAristolochia (Belgium): 3939OxyELITE Pro period (Hawaii)Acute hepatitis cases of unknown cause after a weight-loss or muscle supplement; 24used OxyELITE ProOxyELITE Pro period (Hawaii): 2929TurmericAdjudicated liver-injury cases in the U.S. Drug-Induced Liver Injury Network, 2004–2022Turmeric: 1010Aristolochia, first reportWomen with rapidly progressive renal fibrosis after one slimming regimen, Brussels: 2index cases, 7 found by surveyAristolochia, first report: 991101001,000Each bar uses its own definition, so the bars rank scale of investigation, not comparativerisk.What each investigation counted, phone layoutLead and chromium, cinnamon applesauceCases with blood lead ≥ 3.5 µg/dL after eating a recalledproduct, 44 States, DC and Puerto RicoLead and chromium, cinnamon applesauce: 566566Ephedra alkaloidsAdverse-event reports to FDA reviewed for causation, June1997 to March 1999Ephedra alkaloids: 140140Aristolochia (Belgium)Patients with end-stage nephropathy who had prophylacticsurgery; 18 had urothelial carcinomaAristolochia (Belgium): 3939OxyELITE Pro period (Hawaii)Acute hepatitis cases of unknown cause after a weight-loss ormuscle supplement; 24 used OxyELITE ProOxyELITE Pro period (Hawaii): 2929TurmericAdjudicated liver-injury cases in the U.S. Drug-Induced LiverInjury Network, 2004–2022Turmeric: 1010Aristolochia, first reportWomen with rapidly progressive renal fibrosis after oneslimming regimen, Brussels: 2 index cases, 7 found by surveyAristolochia, first report: 99Log scale; each bar uses its own definition.
MMWR 2025;74(14):239–244; Haller & Benowitz, NEJM 2000; Nortier et al., NEJM 2000; MMWR 2013;62(40):817; Halegoua-DeMarzio et al., Am J Med 2023; Vanherweghem et al., Lancet 1993.
Data table
Counts as published
CaseWhat was countedNumber
Cinnamon applesauceCases (blood lead ≥ 3.5 µg/dL within 3 months of eating a recalled product)566
EphedraAdverse-event reports reviewed, June 1997 to March 1999140
Aristolochia, Belgian cohortPatients who had prophylactic removal of kidneys and ureters39
OxyELITE Pro periodAcute hepatitis cases, Hawaii, May–October 2013 (24 used OxyELITE Pro)29
TurmericAdjudicated DILIN cases, 2004–202210
Aristolochia, first reportWomen with rapidly progressive interstitial renal fibrosis after the same slimming regimen (2 index cases and 7 found by survey)9

The bars show the size of each investigation; none of them is an incidence rate, so they do not rank the risk of one botanical against another.

Identity

A substituted root caused kidney failure and urothelial cancer; an identity test that cannot read extracts produced a disputed verdict

Of 39 patients with aristolochia nephropathy who had prophylactic surgery, 18 had urothelial carcinomaPeer-reviewed cohort
Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342(23):1686–1692. Prevalence 46% (95% CI 29–62%).
Data table
Histology of 39 surgical specimens
FindingPatients
Urothelial carcinoma, ureter or renal pelvis (or both)17
Urothelial carcinoma, bladder (papillary tumor)1
Mild-to-moderate urothelial dysplasia19
Normal urothelium2
Total39

An identity test fit for the material, run on every lot before use, is the control that would have stopped the substitution.

Explanation, details and sources

In Brussels, a slimming clinic changed its regimen in May 1990 to include two Chinese herbs; by 1992 nine young women were in renal failure (Vanherweghem 1993). The pills' alkaloid profiles differed from those expected. Nortier and colleagues later reported that Aristolochia fangchi, which is nephrotoxic and carcinogenic, had been supplied in place of Stephania tetrandra by a manufacturing error. FDA now detains imported supplements containing aristolochic acid without physical examination (Import Alert 54-10).

Identity has a second failure mode: the test itself. In February 2015 the New York attorney general halted sales of certain store-brand herbal supplements after DNA barcoding failed to find the labeled plant in most products tested. Reviewers noted that extraction and processing can destroy DNA, so its absence is not proof of substitution (Wu et al. 2017; Ivanova et al. 2016, who called the move premature), and Parveen et al. (2016) advised against universal-primer barcoding as the sole identification of processed material. Since 2007, 21 CFR 111.75(a)(1)(i) has required at least one appropriate identity test of each dietary ingredient before use.

Contamination

Lead chromate in cinnamon reached 566 people, almost all young children, through pouches at about 190 to 300 times FDA's action level

566 cases by case status and by age group (two separate breakdowns of the same total)Government surveillance data
MMWR Morb Mortal Wkly Rep 2025;74(14):239–244 (doi:10.15585/mmwr.mm7414a2). The middle node joins two separate tallies; the figure implies no link between a case's status and its age group. Age was not reported for 3 cases.
Data table
Cases, November 2023 to April 2024
GroupCasesShare
Confirmed (venous test, no other significant lead source)13023.0%
Probable (venous test; other sources possible or not assessed)40170.8%
Suspected (capillary or unspecified test)356.2%
Under 2 years31155.2% of 563 with age reported
2 to 5 years23141.0% of 563
6 years and older213.7% of 563
Age not reported3–

Case-status shares are of all 566 cases; age shares are of the 563 cases with age reported, as in the MMWR table. Children under 6 were 542 (96% of 566).

Lead in pouches from affected homes against FDA's action level for fruit-based baby foodGovernment data and guidance
Lead in recalled cinnamon applesauce pouches was 1.9 to 3.0 ppm, about 190 to 300 times FDA's 10 ppb action level for fruit-based food for babies and young childrenLead concentration, ppm (log scale)Pouches from affected homesPouches from affected homes: 1.9–3.0 ppm1.9–3.0 ppmFDA action level for fruits (finalguidance, 2025)FDA action level for fruits (final guidance, 2025): 10 ppb = 0.010 ppm10 ppb = 0.010 ppm0.0010.010.1110About 190 to 300 times the action level (MMWR: “nearly 200–300 times”). Highest venous blood lead in a case:39.3 µg/dL.
MMWR 2025;74(14):239–244; FDA, Action Levels for Lead in Processed Food Intended for Babies and Young Children, final guidance (90 FR 1135, Jan. 7, 2025).

Testing incoming spice lots for lead and qualifying the spice supplier were the missing controls; highest venous blood lead in a case was 39.3 µg/dL.

Explanation, details and sources

FDA issued a public health alert on October 28, 2023; the distributor recalled the product the next day, and the recall was later expanded to 2,998,088 pouches. On February 29, 2024 FDA reported that the lead and chromium came from lead chromate. A case had a blood lead level of 3.5 µg/dL or more within three months of eating a recalled product. The within-person maximum venous level ranged from 3.5 to 39.3 µg/dL (median 7.2). The MMWR authors write that "increased product testing is essential to identifying contaminated products."

Dose, form and susceptibility

Green-tea EGCG raised liver enzymes at 800 mg a day in supplement trials, and turmeric injury clustered in one genotype

EGCG intake from green tea and from supplements, against the 800 mg-per-day level linked to raised transaminasesAgency scientific opinion
EFSA 2018: green tea infusions provide 90 to 300 mg EGCG per day on average and up to 866 mg for high consumers; supplements provide 5 to 1,000 mg; intakes of 800 mg per day or more from supplements raised serum transaminases in trials≥ 800 mg/day from supplements: transaminases rose in trialsGreen tea infusion, mean intakeGreen tea infusion, mean intake: 90–300 mg/day90–300 mg/dayGreen tea infusion, high consumersGreen tea infusion, high consumers: up to 866 mg/dayup to 866 mg/dayFood supplements, daily doseFood supplements, daily dose: 5–1,000 mg/day5–1,000 mg/day02004006008001,000EGCG, mg per dayIn interventional trials, ≥ 800 mg EGCG per day taken as a food supplement produced a statistically significant risein serum transaminases versus control (EFSA ANS Panel, 2018). Tea prepared traditionally was consideredgenerally safe at reported intakes.Same plant, different form and dose
EFSA ANS Panel. Scientific opinion on the safety of green tea catechins. EFSA Journal 2018;16(4):e05239 (doi:10.2903/j.efsa.2018.5239).

Dose and exposure data: EGCG and curcumin dose–exposure studies · benchmark-dose explorer

Turmeric liver injury clustered in carriers of one immune-system gene variantPeer-reviewed case series
Turmeric-associated liver injury in DILIN: the HLA-B*35:01 allele frequency was 0.450 among cases against 0.056 to 0.069 in population controls; 7 of 10 patients carried the alleleHLA-B*35:01 allele frequencyCases: 0.45010 turmeric cases (DILIN)0.450Population controls: 0.056 to 0.069Population controls0.056–0.0690.00.10.20.30.40.57 of 10 patients carried the allele (2 homozygous). Latency 1 to 4 months; 5 hospitalized, 1 died. All 7products tested contained turmeric; 3 also contained piperine.
Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric: a growing problem. Ten cases from the Drug-Induced Liver Injury Network. Am J Med 2023;136(2):200–206.

A safe history in one form and dose does not transfer to a concentrated extract, a higher dose or a susceptible person.

Explanation, details and sources

EFSA estimated mean EGCG intake from green tea infusions at 90 to 300 mg a day and up to 866 mg for high-level consumers, while supplements supply 5 to 1,000 mg. It concluded that tea prepared traditionally is generally safe at reported intakes, but that interventional trials show a statistically significant rise in serum transaminases at 800 mg EGCG a day or more taken as a supplement.

Dose was also the legal question for ephedra. A 2005 district court blocked enforcement of the ban for products at 10 mg a day or less; the Tenth Circuit reversed in 2006, holding that FDA "reasonably concluded that there is no recommended dose of EDS that does not present an unreasonable risk." In the aristolochia cohort, cumulative doses above 200 g were associated with a higher risk of urothelial carcinoma.

In the turmeric series, three of seven products tested also contained piperine (black pepper); the authors suggest the rise in cases may reflect use patterns or combination with black pepper.

Unlawful ingredients

Substances that are not dietary ingredients, from DMAA to tianeptine, were sold as supplements until warning letters, import alerts and prosecutions intervened

Poison-center cases involving tianeptine: 4 in 2013, about 350 in 2024Agency data
Poison control center cases involving tianeptine rose from 4 in 2013 to about 350 in 2024, per FDA citing the National Poison Data System0100200300400201320162019202220242013: 4 cases2024: about 350 cases4 (2013)about 350 (2024)Tianeptine is not approved by FDA for any medical useand “is not a dietary ingredient”.Only the two endpoint years are published on FDA's page; thedashed line joins them and shows no yearly data.
FDA, "Tianeptine Products Linked to Serious Harm, Overdoses, Death" (content current as of May 9, 2025), citing the National Poison Data System.

A legal-status review before purchase, and a certificate of analysis checked against an independent test, address both failure routes. Recall counts: drug recalls of supplements, supplement food recalls.

Explanation, details and sources

FDA states that "DMAA is not a dietary ingredient" and considers it an unsafe food additive in supplements; an appeals court affirmed in 2019. In the OxyELITE Pro and Jack3d case, the indictment alleged that DMAA was imported with false certificates of analysis and represented to some retailers as a natural plant extract; the distributor pleaded guilty in 2019 to conspiracy involving mislabeled food. A separate 2013 hepatitis cluster in Hawaii, in which 24 of 29 patients had used OxyELITE Pro, led to a recall that year.

Tianeptine is not approved by FDA for any medical use, and FDA states it "is not a dietary ingredient." For kratom, FDA's Import Alert 54-15 treats supplements that are or contain Mitragyna speciosa as adulterated because they contain a new dietary ingredient without adequate safety information; in July 2025 FDA recommended scheduling concentrated 7-hydroxymitragynine products, excluding natural leaf products.

Recall records show the same pattern at scale: see FDA drug recall records for products sold as supplements on Legal status and food recall records described as dietary supplements on the Regulatory overview.

Which control would have caught it

By this page's assessment, identity testing or adverse-event surveillance would directly have caught seven of the eight cases; claims review, none

Eight failures against seven controlsQualitative assessment by EUTECNIQ
Qualitative matrix of eight documented failures against seven controls: filled circle, the control would directly have detected or prevented the failure; half circle, partly; open circle, little; dash, not applicableIdentity test fitfor the materialSupplier andCOA verificationElement andcontaminanttestingLegal-statusand NDI reviewDose andexposure limitsAdverse-eventsurveillanceClaims reviewAristolochia substitutionAristolochia substitution · Identity test fit for the material: highAristolochia substitution · Supplier and COA verification: mediumAristolochia substitution · Legal-status and NDI review: lowAristolochia substitution · Adverse-event surveillance: mediumEphedra alkaloidsEphedra alkaloids · Legal-status and NDI review: mediumEphedra alkaloids · Dose and exposure limits: mediumEphedra alkaloids · Adverse-event surveillance: highEphedra alkaloids · Claims review: lowDMAADMAA · Identity test fit for the material: highDMAA · Supplier and COA verification: highDMAA · Legal-status and NDI review: highDMAA · Adverse-event surveillance: lowOxyELITE Pro hepatitis clusterOxyELITE Pro hepatitis cluster · Legal-status and NDI review: mediumOxyELITE Pro hepatitis cluster · Adverse-event surveillance: highDNA-barcode testing of retailproductsDNA-barcode testing of retail products · Identity test fit for the material: highDNA-barcode testing of retail products · Supplier and COA verification: mediumTurmeric liver injuryTurmeric liver injury · Dose and exposure limits: mediumTurmeric liver injury · Adverse-event surveillance: highLead chromate in cinnamonLead chromate in cinnamon · Identity test fit for the material: lowLead chromate in cinnamon · Supplier and COA verification: highLead chromate in cinnamon · Element and contaminant testing: highLead chromate in cinnamon · Dose and exposure limits: mediumLead chromate in cinnamon · Adverse-event surveillance: mediumTianeptine and kratomTianeptine and kratom · Identity test fit for the material: mediumTianeptine and kratom · Supplier and COA verification: lowTianeptine and kratom · Legal-status and NDI review: highTianeptine and kratom · Adverse-event surveillance: highTianeptine and kratom · Claims review: lowwould directly detect or preventpartlylittle effectnot applicableJudgment by EUTECNIQ from the published record of each case; not a regulatory finding.Qualitative matrix of failures against controls, phone layout: for each case, the controls that would have detected or prevented itAristolochia substitutionIdentity test fit for the materialSupplier and COA verification (partly)Adverse-event surveillance (partly)Ephedra alkaloidsAdverse-event surveillanceLegal-status and NDI review (partly)Dose and exposure limits (partly)DMAAIdentity test fit for the materialSupplier and COA verificationLegal-status and NDI reviewOxyELITE Pro hepatitis clusterAdverse-event surveillanceLegal-status and NDI review (partly)DNA-barcode testing of retail productsIdentity test fit for the materialSupplier and COA verification (partly)Turmeric liver injuryAdverse-event surveillanceDose and exposure limits (partly)Lead chromate in cinnamonSupplier and COA verificationElement and contaminant testingDose and exposure limits (partly)Adverse-event surveillance (partly)Tianeptine and kratomLegal-status and NDI reviewAdverse-event surveillanceIdentity test fit for the material (partly)directlypartlyEUTECNIQ judgment, not a regulatory finding.
EUTECNIQ judgment from the published record of each case on this page, cited in the sections above; not a regulatory finding.

The proposed EUTECNIQ quality system would put identity, contaminant and legal-status checks before purchase and release, and monitor adverse events after.

Explanation, details and sources

Identity testing addresses substitution (aristolochia), undeclared synthetic substances (DMAA) and unsuitable methods (DNA barcoding of extracts). Supplier qualification with independent verification of certificates addresses falsified certificates (DMAA) and adulterated spice (lead chromate). Element testing addresses lead. Legal-status review addresses substances that are not dietary ingredients. Adverse-event surveillance is how the ephedra, OxyELITE Pro, turmeric and tianeptine signals were found. These controls would be designed and run by a company that does not yet exist; they describe intent, not performance.

Historical use versus evidence

Four large randomized trials of widely used botanicals found no benefit over placebo on their primary outcomes

Primary results of four placebo-controlled trials, each on its own scalePeer-reviewed trials
Four large randomized placebo-controlled trials of widely used botanicals: none found a benefit over placebo on its primary outcomeTrialPrimary result versus placeboGinkgo biloba (GEM)JAMA 2008 · 3,069 adults aged 75+ · 120 mg twice daily · median 6.1 yearsHR 1.12 (0.94 to 1.33)0.81.01.21.41.12Saw palmetto (CAMUS)JAMA 2011 · 369 men · 320, then 640, then 960 mg/day · 72 weeksExtract: -2.20 pointsExtract -2.20Placebo: -2.99 pointsPlacebo -2.99Difference 0.79 points, favoring placeboEchinacea angustifoliaNEJM 2005 · 399 volunteers given rhinovirus · 3 extracts: supercritical CO₂, 60% and20% ethanolNo statistically significant effect on infection rate or symptomseverityBlack cohosh (HALT)Ann Intern Med 2006 · 351 women · 160 mg/day · 1 yearHormone therapy -4.06 (-5.93 to -2.19)Hormone therapyHerbal arms: within 0.55 per day of placeboHerbal arms-6-4-20Each trial tested one product, dose and population; a null result does not settle every preparation of the plant.Four large botanical trials and their primary results, phone layoutGinkgo biloba (GEM)JAMA 2008 · 3,069 adults aged 75+ · 120 mg twice daily ·median 6.1 yearsIncident dementia: hazard ratio 1.12 (95% CI0.94–1.33)Saw palmetto (CAMUS)JAMA 2011 · 369 men · 320, then 640, then 960 mg/day ·72 weeksAUA symptom score change: −2.20 extract vs −2.99placeboEchinacea angustifoliaNEJM 2005 · 399 volunteers given rhinovirus · 3 extracts:supercritical CO₂, 60% and 20% ethanolNo statistically significant effect on infection rate orsymptom severityBlack cohosh (HALT)Ann Intern Med 2006 · 351 women · 160 mg/day · 1 yearHot flashes per day: herbal arms within 0.55 ofplacebo; hormone therapy −4.06 (95% CI −5.93 to−2.19)A null result applies to the product, dose and population tested.
DeKosky ST et al. JAMA 2008;300:2253–2262; Barry MJ et al. JAMA 2011;306:1344–1351; Turner RB et al. N Engl J Med 2005;353:341–348; Newton KM et al. Ann Intern Med 2006;145:869–879.
Data table
Primary outcomes as reported
TrialParticipants, dose, durationPrimary result
Ginkgo biloba (GEM)3,069 aged 75+; 120 mg twice daily; median 6.1 yearsDementia HR 1.12 (95% CI 0.94–1.33; P = .21)
Saw palmetto (CAMUS)369 men; 320, 640, then 960 mg/day; 72 weeksAUASI change −2.20 vs −2.99 placebo; difference 0.79 favoring placebo (1-sided P = .91)
Echinacea angustifolia399 volunteers challenged with rhinovirus; three extractsNo statistically significant effect on infection rate or symptom severity
Black cohosh (HALT)351 women; 160 mg/day; 1 yearNo difference from placebo in vasomotor symptoms (herbal arms within 0.55 symptoms per day on average), except worse symptom intensity at 12 months with multibotanical plus soy; hormone therapy −4.06 (95% CI −5.93 to −2.19)

Long use shows that people chose a plant; a randomized trial measures whether a defined product did what was claimed.

Explanation, details and sources

Each trial tested one characterized product, at a stated dose, in one population, against placebo. The echinacea trial compared three root extracts made by supercritical CO₂, 60% ethanol and 20% ethanol; none differed from placebo. In CAMUS, tripling the saw palmetto dose did not separate it from placebo. A null result applies to the product, dose and population tested. Safety and efficacy are separate questions: a clean safety record says nothing about benefit, and a benefit claim needs human evidence. Trial design is covered on Clinical research.

No disease claims

A disease claim subjects a supplement to regulation as a drug, so this site makes none

How a statement about a dietary supplement is classifiedStatute and regulation
How a statement about a dietary supplement is classified: a claim to diagnose, treat, cure, mitigate or prevent disease makes the product subject to regulation as a drug unless it is an authorized health claim; a structure/function statement needs substantiation, a disclaimer and notification to FDA within 30 daysA statement on a label,website or advertisementIntended use can be shown byclaims in labeling, advertisingand on the internetDoes it claim todiagnose, treat,cure, mitigate orprevent a disease?Disease claimThe product is subject to regulation asa drug, unless it is an authorized healthclaim it qualifies for (21 CFR 101.93(f))YesStructure/function statementAllowed for supplements under FD&CAct § 403(r)(6), with three conditionsNoSubstantiationTruthful and not misleadingDisclaimer“This statement has notbeen evaluated by theFood and DrugAdministration…”Notification to FDAWithin 30 days after firstmarketingHow a statement about a dietary supplement is classified, phone layoutA statement on a label, website or advertisementIntended use can be shown by claims in labeling,advertising and on the internetDoes it claim to diagnose, treat, cure, mitigate orprevent a disease?Yes: disease claimRegulated as a drug unless an authorized health claimapplies (21 CFR 101.93(f))No: structure/function statementNeeds substantiation, the FDA disclaimer and notificationwithin 30 days of first marketing (21 CFR 101.93)
21 CFR 101.93(a), (c) and (f), current to Oct 21, 2026; FD&C Act § 403(r)(6) (21 U.S.C. 343(r)(6)); FDA, "Is It a Cosmetic, a Drug, or Both?" on intended use.

The full course explains the line between structure/function and disease claims.

Academy: Course 10, Why no disease claims

Ask how they would be specified for an ingredient you work with.

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