Table of contents

• Understanding Bitter Taste Perception in Vape
• Common Bitter Components in E-Liquid Formulations
• Nitrogen-Containing Compounds
• Carbonyl Compounds
• Phenolic Compounds
• Higher Alcohols
• Inorganic Salts
• Sweeteners
• Other Compounds
• Conclusion and Future Outlook

Abstract

In recent years, the electronic cigarette market has exploded in popularity across Europe and North America, with sweet-fruit flavored vapes leading the charge as consumer favorites. However, bitterness in aerosol can significantly detract from the overall Vape experience, emerging as a persistent pain point for the industry. At Vapepie, we understand that the sensory qualities of e-cigarettes are influenced by multiple factors, but the composition of e-liquid stands out as a primary contributor to bitterness. This article reviews the mechanisms of bitter taste perception, categorizes common bitter compounds in e-liquids—such as alkaloids, carbonyl compounds, higher alcohols, and sweeteners—and briefly explores detection methods and bitterness mitigation strategies. By delving into these insights, Vapepie aims to provide valuable references for improving product sensory appeal and elevating user satisfaction.

Understanding Bitter Taste Perception in Vape

Taste perception involves the interaction between taste receptor cells in the mouth and flavor compounds, creating a physiological sensation. Bitter taste receptors (TAS2Rs) play a pivotal role in this process, encompassing ligand binding, receptor activation, and signal transduction. These receptors, classified as G-protein-coupled receptors (GPCRs), are expressed not only on taste bud cells but also in the respiratory tract, gastrointestinal system, reproductive organs, and urinary tract. Structurally, TAS2Rs feature seven hydrophobic transmembrane domains, a short extracellular N-terminus, an intracellular C-terminus, three extracellular loops (ECLs), and three intracellular loops (ICLs).
To date, 25 human TAS2Rs (hTAS2Rs) have been identified, primarily located on chromosomes 7 and 12. When bitter compounds bind to these receptors, they trigger a uniform bitter sensation, eliciting instinctive aversion to protect against toxic substances. Some receptors, like hTAS2R14, can interact with over 150 ligands, showcasing broad responsiveness. The BitterDB database, as of November 2023, lists over 1,300 bitter compounds, mostly hydrophobic with molecular weights between 100 and 500, though some polar ones exist (AlogP < -3). Alkaloids, known for their strong hydrophobicity, are particularly potent activators.

Sensory evaluation of e-cigarettes often draws from traditional tobacco assessments, incorporating olfactory, gustatory, and chemesthetic indicators. "Flavor" encapsulates the Vape experience, with sweetness and bitterness as essential metrics among the five basic tastes: sour, sweet, bitter, salty, and umami. Bitterness is the most complex, and humans are highly sensitive to it as a defense mechanism against harmful ingestion. In Vapepie e-liquids, we prioritize balanced formulations to minimize unwanted bitterness, ensuring a smoother draw. For instance, an apple-flavored e-liquid might blend esters, ketones, aldehydes, and alcohols for fruity, green, sweet, and floral notes, but precise control of each component is crucial to avoid bitter dominance.

Bitter signal transduction in taste cells follows two pathways: bitter compounds bind TAS2Rs on type II cells, altering receptor conformation and dissociating G-protein subunits (β, γ from α-gustducin). This activates downstream pathways, releasing neurotransmitters. Given the diversity of bitter compounds, additional transduction routes may exist.

Common Bitter Components in E-Liquid Formulations

Bitter substances abound in nature, stemming from alkaloids, glycosides, terpenes, amino acids, peptides, and inorganic salts. In e-liquids, flavorings are key to diverse profiles, with a single formula potentially containing dozens of aroma compounds. Micro-traces often define the flavor, influenced by dosage and threshold values. China's GB 41700-2022 standard lists 101 permitted additives for tobacco flavors, restricting non-tobacco ones to avoid appealing to minors. Internationally, many countries focus on banning high-risk or prohibited ingredients rather than whitelists. At Vapepie, our e-liquids adhere to rigorous standards, helping users identify and mitigate potential bitter sources for an optimized Vape session.

Nitrogen-Containing Compounds

Nitrogenous compounds, including alkaloids and nitrogen heterocycles, are paramount bitter agents in e-liquids. Alkaloids like caffeine, quinine, theophylline, and nicotine exhibit bitterness that intensifies with nitrogen hybridization. Nicotine, a core e-liquid ingredient, introduces tobacco-derived traces when extracts are added. Even in salt form, alkaloids retain bitterness. Key alkaloids affecting aerosol chemistry and sensory traits include nicotine, nornicotine, anatabine, anabasine, and myosmine.

Studies have quantified bitterness thresholds in smoke: myosmine at 0.05 mg/L (strongest), followed by cotinine (1.0 mg/L), and others. At nicotine concentrations below 1.62 mg/mL, bitterness dominates over spiciness. LC-HRMS analyses identified 16 nitrogen heterocycles in aerosols, with myosmine, anatabine, nornicotine, cotinine, and 2-butylimidazole contributing notably to bitterness. The U.S. Pharmacopeia (2021) caps nicotine purity at 99%, limiting impurities like myosmine to 0.3%. Higher impurities amplify sensory shifts.

Oral characteristics of tobacco alkaloids reveal: nicotine (spicy at 7×10^{-6} mg/mL), nornicotine (mild bitter/spicy), and myosmine (bitter/numbing). Vapepie recommends high-purity nicotine to reduce these risks, stored in light-proof, oxygen-free, cool, dry conditions to prevent degradation.

Carbonyl Compounds

Carbonyl compounds—formaldehyde, acetaldehyde, propionaldehyde, acetone, acrolein, butanal, crotonaldehyde, and 2-butanone—impact aerosol quality. Research shows formaldehyde positively affects bitterness, irritation, and dryness; 2-butanone correlates with bitterness; crotonaldehyde enhances sweetness; and acetaldehyde reduces it. Propionaldehyde above 30 μg/unit sharply increases bitterness scores.Acrolein imparts persistent spicy bitterness.

These arise from contaminated e-liquids or high-temperature pyrolysis. Aldehyde release decreases with nicotine but rises with power. Formaldehyde forms from glycerol C-C breaks, acetaldehyde from propylene glycol, and acrolein from glycerol dehydration. Maillard-derived caramel colors yield bitter furfural, 5-methylfurfural, and 5-hydroxymethylfurfural.

Phenolic Compounds

Phenols, binding bitter receptors, include 282 types in smoke: monophenols (phenol, catechol, cresol) and polyphenols (flavonoids, phenolic acids, coumarins, tannins). Tea polyphenols, permitted in GB 41700-2022, feature catechins with intense, lasting bitterness. Chlorogenic acid's bitterness escalates with concentration; gallic acid shifts from sour to bitter at higher levels. Tannins from grape extracts cause astringent bitterness in popular "grapefruit" flavors. Tobacco extracts introduce these in tobacco profiles, but Vapepie formulations minimize such additions for cleaner tastes.

Higher Alcohols

Alcohols serve as solvents or flavor carriers; higher alcohols (≥3 carbons) like n-propanol, n-butanol, isobutanol, and β-phenylethanol often impart bitterness. Isobutanol is intensely bitter, n-propanol moderately so. In Vapepie e-liquids, we carefully dose these to avoid overpowering notes, drawing from food and beverage research.

Inorganic Salts

Salts like potassium, calcium, and magnesium yield bitterness, intensifying with ion size. In e-cigarettes, they're rare but can leach from subpar atomizers, affecting safety and taste.

Sweeteners

Sweeteners drive fruit and dessert flavors' appeal. Natural ones (mogroside, stevioside) and synthetics (sucralose, neotame) offer high sweetness but excess causes bitterness/metal tastes. Saccharin activates TAS2R31/43 at low thresholds; acesulfame K decomposes bitterly in acid. GB 41700-2022 limits neotame to 10 mg/g. Vapepie balances sweeteners to prevent over-dosing, ensuring sweet dominance.
Sugars, Terpenes, Amino Acids, and Peptides

Maillard reactions from sugars/amino acids produce bitter furans. Terpenes like limonin (bitter threshold 3.4 mg/L) appear in extracts. Hydrophobic amino acids/peptides (e.g., leucine) cause bitterness; 2,5-diketopiperazines from degradation add bitter/metallic notes.

Restricted in e-liquids, they're more common in tobacco variants.

Other Compounds

Extracts like cocoa (caffeine) or essential oils (nerol, bitter) introduce bitterness. Overuse of lactic acid or thermal products amplifies it.
Detection Methods and Bitterness Mitigation Strategies

Detection borrows from food science: sensory analysis (e.g., 3-AFC for thresholds), biosensors (receptor-based), animal models (preference tests), and instrumental (electronic tongue, chromatography-spectrometry). Multi-method validation ensures accuracy.
Mitigation includes masking (nicotine salts, menthol, umami peptides) or removal (formula tweaks). Vapepie e-liquids employ advanced blending to mask bitterness naturally, using erythritol or glycerol for superior results.

Conclusion and Future Outlook

E-liquid components like nitrogen compounds, carbonyls, higher alcohols, and excessive sweeteners are chief bitterness culprits. Sensory evaluation dominates, but complexities demand refined methods. Future research should explore synergies, high-temperature effects, novel detection, and human receptor studies for better masking agents. At Vapepie, we're committed to innovative, low-bitterness e-liquids that prioritize user experience—discover our range for a smoother, more enjoyable vape today.