Vanillin: More Than Just a Favorite Flavoring?

The vanilla bean, which contains vanillin and hundreds of other components, is a valuable agricultural crop thanks to consumers’ fondness for vanilla flavoring in products ranging from ice cream to coffee. Recently, a lower than expected supply of vanilla crops, increased demand for industrial and gourmet grades of vanilla beans, and diminished vanilla bean inventory have contributed to continued price spikes. Consumer demand for natural and organic vanilla and indirect contamination with the photosensitive insecticide Permethrin (>0.02 ppm) at levels greater than permitted for organic products—yet well below the tolerable limits for humans (0.3 ppm in water)—continue to significantly challenge the global vanilla bean supply.

Vanilla beans from the vanilla plant, Vanilla planifolia A., contain in excess of 250 different compounds, which vary with geographical region and curing process (Hartman 2003; Schwarz and Hofmann 2009). The major flavor and potential bioactive component of the vanilla bean is vanillin (4-hydroxy-3-methoxybenzaldehyde), which averages nearly 2%  (Rao & Ravishankar 2000; Hartman 2003). Vanillin is fundamentally a phenol aldehyde that functions as a sweetener as well as a flavor enhancer in a spectrum of food matrices.

Vanilla, particularly vanillin, extends its impact beyond orosensory attributes. Within food systems, vanillin may inhibit lipid oxidation and reduce food spoilage initiated by several genera of yeasts (Fitzgerald et al. 2003).

The pharmaceutical properties of vanilla have at least a 700-year history of applications, including but not limited to relief of fevers, melancholy, and hysteria and use for neurostimulation and as an aphrodisiac (Bythrow 2005). More contemporary evidence indicates vanillin may function as a sunscreen (Lee et al. 2014), reduce activity of some inflammatory pathways (Khuda-Bukhsh et al. 2014), relax vasculature (Raffao et al. 2015), serve as an anti-mutagen (Deb et al. 2011), and induce apoptosis of specific cancer cell lines (Ho et al. 2009).

UV-B radiation induces DNA damage when skin is exposed to excessive sunlight. Preliminary evidence from in vitro studies suggest 10–100 μM (1.5–15 ppm) vanillin may contribute to a significant decrease in several pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6). It may modulate the production of anti-inflammatory cytokines, including epidermal growth factor (EGR), fibroblast growth factor (FGF-2), and transforming growth factor (TGF-β1).

Many sunscreen products on the market in the United States contain vanilla, yet the concentration of vanillin in them is unknown. These vanilla-labeled products typically do not ascribe any potential benefits to vanillin per se other than a favorable fragrance. However, potential UV-B protection may be possible via conversion of vanillin to veratraldehyde and then 3,4-dimethoxy isoamyl cinnamic acid, which can provide UV-B protection at 10 ppm (Wahyuningsih et al. 2002).

There appear to be several molecular targets where vanillin may blunt or inhibit the progression of some forms of cancer or promote tumor apoptosis. Apoptosis via the extrinsic (death receptor) or intrinsic (mitochondrial) pathways involve several key enzyme systems that alter DNA repair. The series of events that affect apoptosis and even angiogenesis are molecular targets of plant-derived products, such as vanillin. In this case, preliminary evidence indicates vanillin may induce apoptosis of HeLa cells (human cervical cancer cell line) by activating tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Vanillin, at doses of 1–8 mM (~152–1,200 ppm) appears to inhibit TRAIL-induced phosphorylation of p65 (a transcription factor) and thus transcriptional activity of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) (Lirdrapamongkol et al. 2010). NF-κB is a key transcription factor that is central to DNA transcription and cellular inflammatory responses. Importantly, this concentration of vanillin did not significantly compromise the viability of normal cells.

Vanillin has been shown to reduce hepatocellular malignancies by attenuating MMP-9 (matrix metalloproteinase-9) expression within tumor cells (Liang et al. 2009). This in vitro research with HepG2 cells exposed to ~75–750 ppm demonstrated expression and activation of this protein complex while not presenting any adverse effects on normal cell viability. Similar results were reported following vanillin exposure (up to 1,000 ppm) to human colorectal cancer cell lines (HT-29; NIH/3T3) (Ho et al. 2009). In this case, vanillin induced apoptosis and arrested the G0/G1 phase of the cell replication cycle.

Historical evidence and contemporary research indicate vanillin has impact beyond its use as a popular flavoring agent. From a food science perspective, vanillin may reduce lipid oxidation and decrease peroxide values in food matrices (Burri et al. 1989; Anuradha 2013). A number of cell culture studies suggest vanillin may also exhibit anticarcinogenic functions through a variety of mechanisms. Thus, vanilla appears to be more than a favorite flavor. It may also be an emerging component in a healthful diet.




Roger Clemens, DrPH, CFS,
Contributing Editor
Adjunct Professor,
Univ. of Southern California School of Pharmacy,
Los Angeles, Calif.
[email protected]