Navigating Natural Flavor Regulations
By: Dr. Luke Grocholl,
Regulatory Affairs Expert, Flavors & Fragrances
In November 2015, the US FDA sought public feedback on the use of the term “natural” in food labeling, receiving over 7,000 comments illustrating diverse opinions on the term. Some found it surprising that the FDA does not have an existing definition for "natural" food. However, this is not unique to the United States. No major regulatory agency worldwide defines natural ingredients in food, except for natural flavors. The US FDA, EFSA, Japanese Ministry of Health, and other regions have clear requirements for labeling flavors as "natural." Definitions for natural flavors can vary significantly globally, and analytical verification methods are likewise diverse. This article provides a brief description of regional natural flavor definitions and information on analytical verification methods.
US Natural Flavors
Natural flavors are defined in the United States under FDA Regulation 21 CFR 101.22. The key definitions in this regulation are: “The term natural flavor or natural flavoring means … any product of … plant material, meat, …, eggs, dairy products, or fermentation products thereof, whose significant function in food is flavoring….” This definition identifies many types of natural raw materials and some methods for producing raw materials, but it can be summarized easily.
NATURAL FLAVORS DEFINITION (USA)
Under US regulations, natural flavors are derived from raw materials without any artificial constituents, where artificial refers to synthetic, mineral, or petrochemical substances. Raw materials that meet the natural definition include animal products (meat, eggs, dairy), botanical sources, and microbiological sources (including fermentation products). The natural status of flavors is not affected by the use of raw materials from genetically modified organisms (GMOs), including those modified using synthetic biology methods.
Manufacturing processes for declaring flavors as natural have minimal restrictions. For instance, chemical transformation of natural flavors using inorganic catalysts still fulfills the US natural flavor requirement. An example is the production of 2-methyl-2-pentenoic acid (FEMA# 2923) through the base-catalyzed condensation of propionaldehyde obtained from fusel oil. Fusel oil, a by-product of alcohol fermentation, is considered a natural raw material. The intermediate is isolated through distillation, followed by chemical transformation using a catalyst, oxidation through heating in air, and further purification via distillation.
Figure 1.Synthesis of natural 2-methyl-2-penenoic acid
Analytical Verification of US Natural Flavors
Analytical verification of US natural flavors commonly involves carbon-14 (C-14) isotopic analysis. C-14 is formed in the upper atmosphere through the interaction of nitrogen-14 with cosmic ray neutrons. It exists in trace amounts, approximately one part per trillion (ppt), in atmospheric carbon dioxide. When plants absorb atmospheric CO2, they acquire the same C-14 concentration. This concentration is then transferred through other organisms in the food chain and into products such as natural flavors. Synthetic materials derived from petroleum sources do not contain C-14, as it decays over time due to its half-life of 5,730 years. Thus, C-14 analysis, often expressed as percent modern carbon (PMC), indicates the extent of C-14 depletion and thus the degree to which synthetic raw materials are used.
However, certain factors need consideration during C-14 analysis. Atmospheric C-14 levels have varied due to above-ground nuclear testing, peaking in 1963. Consequently, flavoring ingredients obtained from more antiquated materials—such as massoia lactone (FEMA# 3744), which is sourced from massoia tree bark that may be decades old—may exhibit unexpectedly higher C-14 concentrations compared to current atmospheric levels. Regions with heavy fossil fuel usage and poor atmospheric circulation might have lower-than-expected local C-14 levels. While adulteration by adding a C-14 source to a flavor to achieve a false positive for natural is possible, it is challenging and costly. Overall, C-14 analysis represents one of the best tools for verifying the use of natural raw materials in flavor production.
EU Natural Flavors
EU Regulation (EC) 1334/2008 defines natural flavors based on three criteria: 1) obtained through appropriate physical, enzymatic, or microbiological processes; 2) sourced from vegetable, animal, or microbiological materials; and 3) corresponding to substances naturally present and identified in nature.
Similar to the US, the second criterion aligns with the requirement for natural-source raw materials. GMOs are acceptable for natural flavor declarations in both regions. However, the EU mandates that natural flavors be produced solely through traditional food preparation processes, such as heating, cooking, cutting, grinding, pressing, distillation, recrystallization, solvent extraction, enzymatic processes, and fermentation. Synthetic and inorganic catalysts are prohibited, and other chemical catalysts like singlet oxygen, ozone, or UV radiation are also not allowed for manufacturing natural flavors. For example, adsorption onto activated carbon can be used to purify natural flavors but not to facilitate chemical transformations. Hence, the conversion of citronellal (FEMA# 2307) to isopulegol (FEMA# 2962) on silica gel is not considered acceptable. The use of natural organic acids or bases to enhance natural flavor yield is permitted as long as they are not essential for the chemical transformation.
An example of an acceptable EU natural flavor manufacturing process is the production of methyl cyclopentalone (FEMA# 2700) from sugarcane. The process involves crushing and grinding sugarcane into bagasse and heating it to obtain a sugary organic-chemical mixture that can be isolated through heat distillation. Saccharomycetaceae yeast is used for fermentation and distilled into fermentation products like methyl cyclopentenolone, which imparts a caramellic/sweet/coffee taste. Only physical and microbiological processes are employed, meeting the EU's definition of natural flavors.
Figure 2. Synthesis of natural methyl cyclopentenolone
Identified in Nature
In the EU, natural flavors must meet additional requirements beyond raw materials and manufacturing processes. They must correspond to substances naturally present and identified in nature. Verification of this criteria involves comparing the flavoring substance to literature references, such as Fenaroli's Handbook of Flavor Ingredients and The Good Scents Company’s website.
Flavor materials containing optical or geometric isomers are deemed to align with naturally occurring substances if all isomers occur in nature or if they are recognized to develop through natural processes upon isolation. An example is δ-decalactone (FEMA# 2361), which naturally occurs in both the S(-) enantiomer (96.6% EE in raspberries) and R(+) (94.0% EE in peaches). Flavors containing exclusively S or R enantiomers, or any combination including racemic mixtures, meet the "identified in nature" requirement.
Furthermore, ammonium, sodium, potassium, and calcium salts of flavors, as well as chlorides, carbonates, and sulfates, are considered "identified in nature" as long as the parent flavor is identified in nature. For instance, methyl ethyl pyruvic acid (FEMA# 3870) naturally occurs in asparagus, cocoa, and some cheeses. Sodium 3-methyl-2-oxovalerate (FEMA# 3870), although not identified in nature, could be considered natural if it satisfies the other criteria.
Analytical Verification of EU Natural Flavors
Because EU natural flavors have three criteria, analytical verification can be very difficult. C-14 analysis can be used to verify the raw material source is natural, but it is very difficult to confirm the material was manufactured using an acceptable, traditional process. Several methods are used to discern the manufacturing process, but they all have their limitations.
Chiral Analysis
Since some chiral materials are found in nature in only one enantiomer, chiral analysis can be used to verify the material meets the identified in nature criteria. If other enantiomers are found in nature, however, any enantiomeric combination is acceptable. The identification of a racemic mixture alone does not prove that a material is not natural, since enzymatic methods can produce enantiomeric ratios not found in nature and materials can racemate over time, especially if heated, as during a distillation or purification.
Fingerprint Analysis
Some synthetic methods yield known impurities indicative of the synthetic process. For example, when mineral acids are used to convert 2-methyl butanol (FEMA# 3998) to 2-methylbutyric acid (FEMA# 2695) the reaction also yields 2-hydroxy-2-methylbutyric acid. The presence of 2-hydroxy-2-methylbutyric in 2-methylbutryic acid is therefore indicative of a process that is not acceptable as natural in the EU. Although fingerprint analysis is a good method for a few well-known synthetic processes, it is limited to only those known reaction schemes.
Site-Specific DNMR
Some natural processes result in a known hydrogen-deuterium ratio at specific molecular sites. The determination of naturalness, however, can be quite challenging. Different acceptable natural manufacturing methods, such as extraction, fermentation, or enzymatic conversion, and different natural raw materials can result in a wide range of hydrogen-deuterium ratios. This method is therefore good for a positive test; a known natural method was used, but a negative result may not be definitive for discounting naturalness.
Stable Isotope Ratio Analysis (SIRA)
Stable isotope ratio analysis is similar to site-specific DNMR in that it evaluates the stable isotopic ratio of flavor molecules. Atmospheric oxygen, for example, has a known, stable isotopic ratio. Oxidation of alcohols to acids using mineral acids results in an oxygen isotopic ratio that differs from the natural atmospheric ratio. Like DNMR, SIRA has similar shortcomings. Different, acceptable manufacturing methods can result in different isotope ratios. Fermentation, for example, may scramble oxygen-isotope ratios. Like DNMR, SIRA is good for positive results, showing a stable isotope ratio resulting from a known natural manufacturing method, but negative results may not be definitive.
EU Natural Flavor Summary
The EU definition of natural flavors is stricter than that in the US. As a result, EU natural flavors meet the US requirement, but the reverse is not necessarily true. The EU has natural requirements for the manufacturing method as well as the raw material origin. Confirmation of the natural method can be very difficult, and all the analytical methods have their shortcomings. Additionally, the EU requires that materials declared as natural flavors be identified in nature. This excludes some flavors, such as vanillyl butyl ether (FEMA# 3796), which is produced from the fermentation of vanillyl alcohol (FEMA# 3737). However, there is no identified natural occurrence of vanillyl butyl ether.
Global Natural Flavor Definitions
Different global entities have their own distinct definitions of natural flavors, which cannot be exhaustively covered in this article. However, a brief overview of some global definitions is presented. For instance, India defines natural flavors as those exclusively derived from vegetables through physical processes, excluding microbiological processes. Japan, like the US, places restrictions on the manufacturing method but has a limited list of permissible plants and animals for sourcing natural flavors. In Canada, the emphasis is placed on artificial flavors, with the requirement that materials not sourced from plants, animals, or microbiological sources be labeled as artificial. Conversely, natural flavors can be declared when derived from natural sources. Australia and New Zealand revised their regulations in 2002, removing the differentiation between natural and artificial flavors. Although not a regulatory requirement, the Flavor and Fragrance Association of Australia and New Zealand (FFAANZ) suggests following EU requirements.
To address the variability in natural flavor definitions, some regions refer to guidelines provided by the International Organization of the Flavor Industry (IOFI). These guidelines, based mainly on EU regulations, emphasize that natural flavors should be derived from natural raw materials obtained through physical, enzymatic, or microbiological processes and identified in nature.
Summary of Global Definitions of Natural Flavors |
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Summary
Regulatory definitions of natural flavors vary significantly among different regions. Australia, for instance, does not provide a specific definition for natural flavors, while the EU requires adherence to criteria including raw materials, manufacturing methods, and identified natural ingredients for labeling products as natural flavors. Since the EU regulation is one of the most proscriptive, EU natural flavors meet most global definitions, but not all. Japan, for example, has a limited list of acceptable raw materials for natural flavors, whereas the EU and most other countries and regions do not. Although public perception may differ, GMOs do not preclude a raw material from being a natural source. Analytical verification of natural sourcing can be very difficult. Carbon-14 analysis is a good tool for verifying a flavor was made exclusively from natural raw materials, but it has some shortcomings. Analytical verification of manufacturing processes is very difficult and often only definitive for verifying specific natural processes used for some select materials.
With the many different definitions of natural flavors, it is important to know the regions where the flavors are marketed. A thorough understanding of the raw materials used and the manufacturing method is often needed to determine if the substance meets the local definition of a natural flavor.
Footnotes
1Synthetic biology is a type of genetic modification which differs from traditional GM methods in that the gene used to modify the organism is manufactured rather than spliced from a different organism.
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