PHARMACOGNOSY AND SAFETY

OF FOOD SUPPLEMENTS

Dr C. Rouger, Dr J. Gabaston, Prof. P. Waffo-Téguo

UFR Sciences Pharmaceutiques

UR Œnologie (ISVV)

2nd Indian - French Symposium Hyderabad - Bordeaux

Plants with health benefits and biomolecules of interest

27th - 29th November 2019

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Risks with

herbal food

supplements

Botanicals in food supplements:

➢ Food plants, medicinal plants, novel food…

➢ Powders, extracts, essential oils…

Lenssen K. G.M. et al, Compr. Rev. Food Sci. Food Saf., 2019

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Risks with

herbal food

supplements

Botanicals in food supplements:

➢ Food plants, medicinal plants, novel food…

➢ Powders, extracts, essential oils…

Common belief that natural ingredients are safer than synthetic ones

Risks:

▪ Side effects

▪ Interactions with medicines

▪ Contraindications

Various causes

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Fraud in herbal supplements

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Fraud in herbal supplements

Adulteration: product mixed with other substance(s)

Illegal addition of active synthetic pharmaceuticalingredients

Undeclared amount of other plant species

Substitution: wrong active ingredient

Inappropriate labelling

IMPACT, 2011

• Weight gain

Anabolic steroids

• Weight loss

Sibutramine, synephrine

• Sexual enhancement

PDE-5 inhibitors

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Lack of data

On the labelling

Part of the plant used?

Geographic origin?

Extracts: which extraction solvent? DER?

Concerning the plant usage itself

Plants unknown as food plant

(e.g. Forsythia suspensa, not consumed in Europe)

Non-traditional preparations (e.g. fermentation)

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Contaminants

Pathogenic organisms

Heavy metals

Pesticide residues

Mycotoxins

Aspergillus niger

(www.pasteur.fr)

CdCu Pb

Cr

Aflatoxin B1

Speijers G. et al, Mol. Nutr. Food Res., 2010

Dlugaszewska J. et al, Saudi Pharm. J., 2019

Bacillus cereus

(https://presse.inserm.fr)

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Unauthorised novel food ingredients

Novel food: Regulation (EU) 2015/2283

= “Food that was not used for human consumption to a significant degree within the Union before 15 May 1997”

Submitted to authorisation by the European Commission since 01/01/2018

Risk evaluation by EFSA

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Towards the

safety of herbal

food

supplements

Safety evaluations needed:

➢ Quality of the botanicals: identity and authenticity

➢ Botanicals that can be safely used

➢ Botanicals within safe limits

Regulatory authorities:

➢ EU: European Food Safety Authority (EFSA)

➢ India: Food Safety and Standards Authority of India (FSSAI)

➢ USA: Food and Drug Administration (FDA)

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Guidelines

FDA: “Good Manufacturing Practice regulations for dietary supplements”

EFSA: “Guidance on Safety assessment of botanicals and botanical preparations intended for use as ingredients in food supplements”

List of technical, exposure and toxicological data

Approach for safety assessment

Level A: safety assessment based on available knowledge

Level B: generation of additional (toxicological) data

→ Safety concern

→ No safety concern

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EFSA’s Compendium of Botanicals

www.efsa.europa.eu/en/microstrategy/botanical-summary-report

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Novel food ingredients

Novel food catalogue

http://ec.europa.eu/food/safety/novel_food/catalogue/search

Was only used as/in

food supplement

before 15/05/1997

Safety assessment

under the Novel Food

Regulation required

Further information

required

Not subjected to the Novel

Food Regulation

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Novel food ingredients

Union list of novel foods: Commission Implementing Regulation (EU) 2018/1023 => Authorised novel foods

https://ec.europa.eu/food/safety/novel_food/authorisations/union-list-novel-foods_en

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Addition of certain substances to food

Regulation (EC) No 1925/2006 (Art. 8)

=> The European Commission can place a substance presentinga potential risk in Annex III:

Part A: substances prohibited

Part B: substances allowed under specific conditions

Part C: substances under control (possible harmful effects)

=> The EC can request an evaluation by the EFSA

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Addition of certain substances to food

Assessment:

- Technical data: chemical composition,

manufacturing process, use levels, exposure…

- Biological and toxicological data: ADME, toxicity

Reg. (EC) 1925/2006

Commission Regulation (EU) 2019/650:

Amendment Annex III to Reg. (EC) No

1925/2006

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European Pharmacopoeia’s monographs

Raw material Preparations

ENGLISH TITLE

+ LATIN TITLE

DEFINITION

PRODUCTION

CHARACTERSE.g. Green tea

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European Pharmacopoeia’s monographs

Raw material Preparations

IDENTIFICATION

TESTS

ASSAYTannins

FeCl3

Flavones/Flavonols

Cyanidin reaction

Xanthines

Murexide test

N.B. For pure compounds

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Standardisation of the preparations

Standardised extracts

Quantified extracts

Refined extracts

Other extracts

=> Adjustment to a content of one or more constituents

Ph.Eur. 10.0

Drug Extract Ratio (DER) =quantity of herbal drug used (g)

quantity of extract obtained (g)

ABC-AHP-NCNPR Botanical Adulterants Prevention Program

American Botanical Council – American Herbal Pharmacopoeia – National Center for Natural Products Research

Adulteration reports

Currently: 19 adulterants bulletins & 9 laboratory guidance documents

Known/possible adulterants

Possible safety issues

Analytical methods to detectadulteration

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Methods of detection

= Usually a combination of analyses

› Organoleptic characters

› Macroscopy, Microscopy

› Chromatographic assays (HPTLC, HPLC, LC-MS, GC-MS)

› Other detection methods in development in research

• Spectroscopic assays (NMR)

• Genetic methods (DNA metabarcoding)

› Importance of reference standards (or reference material)

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Concluding

remarks

Official positive list of botanicals, along with:

Maximum doses?

References to quality control tests?

=> Recognition and extension of the BelFrIt list

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Concluding

remarks

Official positive list of botanicals, along with:

Maximum doses?

References to quality control tests?

=> Recognition and extension of the BelFrIt list

Minimum information on the label

Plant Latin binomial name, part of plant

Preparation: type, extraction solvent, DER / standardised preparations

Regular monitoring and surveillance of marketed food supplements

Unclear frontier between plant-based medicines and food supplements

Thank you for your attention

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Axis Molecules of

Biological Interest