Vanillin health benefit by Ray Sahelian, M.D.
April 17, 2016

Vanillin, the major constituent of vanilla beans, is one of the most important aromatic flavor compounds used in foods, beverages, perfumes, and pharmaceuticals and is produced on a scale of more than 10 thousand tons per year by the industry through chemical synthesis.

Chemistry of vanillin
Ferulic acid is an extremely abundant, preformed phenolic aromatic chemical found widely in nature. Ferulic acid is viewed as a commodity scale, renewable chemical feedstock for biocatalytic conversion to other useful aromatic chemicals. Vanillin (4-hydroxy-3-methoxybenzaldehyde), vanillic and protocatechuic acids are catabolic products of ferulic acid degradation. Several substances can convert into vanillin. Most attention is focused on bioconversions of ferulic acid to vanillin. Isoeugenol can also be converted into ferulic acid and then on to vanillin.

Benefits of vanillin
Like many polyphenols found in plants, vanillin has antioxidant and anti-tumor activity.

Brain health
Evid Based Complement Alternat Med. 2015. Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells. Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington's disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties.

Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells.
Eur J Pharm Sci. 2005.
Vanillin, a food flavoring agent, has been reported to show anti-mutagenic activity and to inhibit chemical carcinogenesis. In this study, we examined the effect of vanillin on the growth and metastasis of 4T1 mammary adenocarcinoma cells in BALB/c mice. Mice orally administered with vanillin showed significantly reduced numbers of lung metastasized colonies compared to controls. In vitro studies revealed that vanillin, at concentrations that were not cytotoxic, inhibited invasion and migration of cancer cells and inhibited enzymatic activity of MMP-9 secreted by the cancer cells. Vanillin also showed growth inhibitory effect towards cancer cells in vitro. However, vanillic acid, a major metabolic product of vanillin in human and rat, was not active in these in vitro activity assays. Our findings suggest that vanillin has anti-metastatic potential by decreasing invasiveness of cancer cells. Since vanillin is generally regarded as safe, it may be of value in the development of anti-metastatic drugs for cancer treatment.

Skin protection
Food Chem Toxicol. Jan 2014. Vanillin protects human keratinocyte stem cells against ultraviolet B irradiation.

Vanillin Research
Int J Biol Macromol. 2016. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function. tVanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation.

Inhibition of peroxynitrite-mediated reactions by vanillin.
J Agric Food Chem. 2004.
Several neurodegenerative diseases such as Alzeimer's and Parkinson's as well as septic shock and inflammation involve formation of reactive oxygen and nitrogen species that include peroxynitrite (PON). PON can also react with endogenous antioxidants. Therefore, dietary supplementation with antioxidants may help in these diseases. An exogenous antioxidant, vanillin (4-hydroxy-3-methoxybenzaldehyde), used widely as a food flavoring agent, was evaluated for its ability to scavenge PON and inhibit PON-mediated reactions. Nitration of tyrosine by PON was assessed by high-performance liquid chromatography (HPLC). This reaction was inhibited by vanillin. The oxidation of dihydrorhodamine 123 to fluorescent rhodamine 123 was also inhibited by vanillin. The kinetics of reaction between PON and vanillin was studied by stopped-flow technique. The products of this reaction were analyzed by HPLC, and hydroxyvanillin was identified as one of the five products with absorption at 350 nm. These data demonstrate that vanillin effectively scavenges peroxynitrite in cell-free systems.

Vanillins -- a novel family of DNA-PK inhibitors.
Nucleic Acids Res. 2003.
Non-homologous DNA end-joining (NHEJ) is a major pathway of double strand break (DSB) repair in human cells. Here we show that vanillin (3-methoxy-4-hydroxybenzaldehyde)--a naturally occurring food component and an acknowledged antimutagen, anticlastogen and anticarcinogen--is an inhibitor of NHEJ. Vanillin blocked DNA end-joining by human cell extracts by directly inhibiting the activity of DNA-PK, a crucial NHEJ component. Inhibition was selective and vanillin had no detectable effect on other steps of the NHEJ process, on an unrelated protein kinase or on DNA mismatch repair by cell extracts. Subtoxic concentrations of vanillin did not affect the ATM/ATR-dependent phosphorylation of Chk2 or the S-phase checkpoint response after ionising radiation. They significantly potentiated the cytotoxicity of cisplatin, but did not affect sensitivity to UVC. A limited screen of structurally related compounds identified two substituted vanillin derivatives that were 100- and 50-fold more potent than vanillin as DNA-PK inhibitors. These compounds also sensitised cells to cisplatin. The inhibition of NHEJ is consistent with the antimutagenic and other biological properties of vanillin, possibly altering the balance between DSB repair by NHEJ and homologous recombination.

Vanillin supplier
December 2006 - Borregaard Ingredients announces an immediate 20% price increase for its vanillin and ethyl vanillin product lines. The increase is the result of significant higher costs (energy and raw materials) and imbalance between demand and supply capacity. The shortage of vanillin is caused by a significant drop of world capacity after shut down of two major Chinese producers along with a globally increased demand. More than 2000 MT capacity has disappeared from the market this autumn. The remaining Chinese producers increased the prices for vanillin and ethyl vanillin approximately 20% in September. This has lead to a tremendous increase in demand for vanillin and ethyl vanillin from other sources. “We are sold out the next 3 months. For users of vanillin and ethyl vanillin without contracts it will not be a question of what price they get, but what volume they will be able to source from the market” says Thomas Grys, Director of Borregaard’s vanillin business.

Q. My comment and question is this: I started drinking green tea as a replacement for coffee. I still get some caffeine which has eliminated any withdrawals. But green tea is terribly boring alone so I added an herbal tea from Celestial Seasonings called Madsgascar Vanilla Red. It smells wonderful and the taste is also pleasant. But after a few weeks I noticed an increase in libido. Not a dramatic increase but yet still noticable. Can green tea have this effect. Or is it the vanilla? Or is it a combination of the two.
   A. This is difficult to say, but many herbs have libido enhancing properties, some are subtle and take weeks to work whereas others can work in an hour or a day and are called aphrodisiacs. it could be either the green tea, vanilla, or both.

Q. I came across your vanillin site while looking for additional information on vanillin. Were you aware that vanillin (synthetic vanilla) or 4-hydroxy-3-methoxybenzaldehyde is metabolized the phase II detoxification system in the liver, specifically glucuronidation? From Wikipedia, the free encyclopedia: Glucuronidation is a major inactivating pathway for a huge variety of exogenous and endogenous molecules, including drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids. Those of us with Gilbert’s Syndrome experience severe reactions when ingesting vanillin. I personally experience profound debilitating fatigue with body temperature fluctuation as my temperature drops and I feel extremely cold. Although you may have listed some positive facts for vanillin on your website, I felt it was important to share what I have uncovered.

Taking garlic can make one smell really bad, but I've found taking vanilla makes me smell really good. When I put a single drop of vanilla extract in my coffee just for flavor, I find that I don't even need to wear deodorant. In fact, girls often comment on how good I smell. Some say that I am "delicious." Wow! Is there a scientific basis to my discovery? I mean, some of the stuff they put in deodorants can be downright unhealthy. Wouldn't it be nice to be able to deodorize from the inside out?
    Thanks for sharing this with us, it is a clever idea. Vanillin may be the main chemical that smells nice.

I recently read your article about vanillin. I was wondering if you knew the effects of vanillin when exposed to 450 degree heat, such as a flat iron used for straightening hair. Some hair smoothing systems contain vanillin and I've read that at 430-450 degrees the vapors from vanillin turn to formaldehyde or aldehyde. Is this true? Is this a health hazard?
    This is not a topic I have studied in any detail.