I don’t spend a lot of time on the blog swatting down idiotic ideas about chemicals. It’s a full time job, and (see next post) I already have a full time job. It’s also frustrating work, because the supply of idiocy is apparently beyond limit, and just when you think you’ve seen the most clueless thing yet, they somehow manage to remove another clue and come back around. But over the weekend, several people alerted me to one of the latest ads in Panera Bread’s long-running campaign to convince everyone that their food is chock-full of wholesome goodness. This one takes off after sodium benzoate, and there are little Twitter and Instagram animations talking about how this icky stuff belongs in fireworks, not in your Panera food, right, guys?
If you Google “sodium benzoate”, prepare yourself for a firehose of stupidity. There’s a long list of sites that are convinced that while benzoic acid is a fresh, healthy, natural ingredient, that sodium benzoate is a devilish industrial chemical that will rot your soul. No, really, that’s pretty much how it goes, and since I know that the great majority of the readers here have a good understanding of acid/base chemistry, you all must be furrowing their brows in puzzlement about that one. I’m with you. I think that my favorite, in a way, is the assertion that when sodium benzoate is exposed to ascorbic acid, that it immediately converts to benzene, which cues up a look at benzene’s (most definitely alarming) toxicity. The source for this would have to be this paper from 2008, which analyzed a long list of beverages for benzene contamination, and found that the only detectable levels were in carrot juice intended for infants. Benzene levels correlated with copper and/or iron levels, and the authors believe that the benzoic acid in carrots is catalytically decarboxylated to a small extent during the heat treatment of the juice. But even the sites that don’t bring that up generally work in something about how sodium benzoate causes Alzheimer’s, Parkinson’s, multiple sclerosis, cancers of all types, you name it. And you thought only aspartame could do it all. Somehow, turning fresh, pure benzoic acid into its sodium salt puts the Curse of the Vat onto it, and this evil stain can never be removed, as we all know.
The first idiotic part of this, as the chemists are well aware, is that in foods that contain benzoic acid, a goodly fraction of it is already present as the benzoate anion. In fact, “Determine the proportions of benzoate and benzoic acid in a 0.1M solution of sodium benzoate” is a perfectly good (and perfectly straightforward) problem for an introductory chemistry class. In food, the cation associated with the benzoate is going to be hard to put your finger on, the inside of cells (and food in general) being the gemisch that it is, but sodium is an excellent first choice, considering how much of it is found in living systems. Calcium, technically, is the most common cation in the body, but it gets that title because a lot of it is tied up in bone tissue. Sodium, magnesium, and potassium are probably better bets for intra- and extracellular fluids, although calcium’s definitely a player, too. But it really doesn’t matter much. Benzoic acid is in equilibrium with (whatever) benzoate, and at the likely pH readings in foods (it’s slightly more acidic than acetic acid), you’re going to have a decent amount of the latter.
Benzoic acid is found (as a completely natural metabolite and intermediate) in a huge variety of foods, especially fruits and vegetables – berries are particularly high in it, but it’s also found in aromatic spices such as cinnamon and allspice. There’s not much in meat, but it is found in seafood, and in milk, particularly in fermented milk products such as completely natural, non-GMO yogurt made by people wearing unbleached hemp clothing and singing to each other about their feelings. OK, I’ll try to resist going off like that again (it’s difficult), but it’s certainly true that the bacterial metabolic pathways in fermented milk products like cheese and yogurt produce a good amount of benzoate. (If you’re wondering, chemically, where it comes from, it’s apparently via the microbial breakdown of hippuric acid and phenylalanine, and indirectly from tyrosine as well).
We humans tend to clear benzoic acid out as its conjugate with glycine (which compound is the abovementioned hippuric acid), and I have seen a 1930s biochemistry text that gave this as a laboratory experiment for undergraduates. They suggested that each student drink a solution with several grams of sodium benzoate and then collect their urine over the next few hours, followed by an extractive workup and crystallization to see who produced the best yield of hippuric acid. Such a Urination Derby (or “Piss-off”) experiment is frowned on these days – I used to threaten my lab sections with this one when I was a teaching assistant, but the higher-ups wouldn’t have let me go through with it even if I’d tried. But that’s not because the benzoate is toxic.
This is a comprehensive review on the use of benzoic acids and benzoates in foods, and the folks at Panera could learn a lot from it. Although, it has to be noted, the ones who came up with their benzoate ads could apparently learn a lot from most anything, starting with children’s board books and working up from there. The review points out that benzoic acid is a widely used preservative, but its salts are preferred due to their greater solubility (just as in that old experiment above). It’s mostly used for acidic foods, since it seems to have its greatest antimicrobial effect at pH levels from 2.5 to 4.5 – that is, when the equilibrium is largely towards the benzoic acid side. Put in nonchemical terms, for anyone from Panera who might stumble across this, sodium benzoate turns into benzoic acid when it’s used as a preservative. It’s just a matter of pH, as any high school or freshman chemistry student should be able to explain.
Now to the toxicology and the regulatory aspects. The EC considers benzoic acid together with the benzoate salts, benzaldehyde, and benzyl alcohol, since they are readily interconverted in living systems. They are all GRAS, “generally recognized as safe”. In more detail, that means that (using the regulatory phrasing) “There is no evidence in the available information on the substance that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future“. Classic toxicology on benzoic acid/sodium benzoate is not easy, because it’s so nontoxic. Values up to 5 to 10 grams per kilo have been reported as the median lethal dose in rats, which is a huge, whalloping amount. If true, that’s less acutely toxic than table salt; sodium chloride has an LD50 of about 3 grams/kilo in the rat. Chronic toxic effects, though, most certainly show up if you feed rodents a diet that’s 1% or more benzoic acid by weight (still a mighty dose indeed – see below). There are effects on cells in culture as well, although at levels that would seem difficult to achieve in vivo.
Limits for it in foods are generally set to several hundred mg/kilo (a very generous amount – those are levels that you won’t find for too many other things). You can legally go up to 6000 mg/kg for cooked shrimp and 3000 mg/kg for “vegetable pulps”, though. Average daily intake is recommended as around 5 mg/kilo of body weight per day or less, so you’d think that you might want to lay off the cooked shrimp in vegetable pulp. Actual commercial levels of the compound tend, apparently, to be far lower than those legal upper limits. Studies from Australia, New Zealand, Turkey, Hong Kong and many other countries have found that the actual daily intake is a factor of five or less than that ADI value. There are exceptions, though, particularly with concentrated fruit products and with cheeses and yogurt-like products, which has led to some to call for a re-evaluation of all these intake levels. To give you an idea, the estimate from the review linked to above is that perhaps 5% of the population might be over the 5 mg/kg/day limit, averaged over a typical lifetime. In case you’re wondering, that 1%-by-weight in the food that causes problems in rats would equal some 10 to 20 grams per day in an average human’s diet, a brutal amount that would be impossible to reach in anything approaching a normal diet.
But all that is sanity, backed up by hard data. Panera’s ad is a cute graphic is all about how sodium benzoate is found in fireworks, so it shouldn’t be in your delicious food. The problem is, a goodly number of Panera’s menu items – such as all the ones with cheese, and all the ones with berries – contain plenty of sodium benzoate already, in some proportion with benzoic acid. It’s stupid and disingenuous of them to pretend that they’re protecting their customers from evil industrial chemicals, when the same stuff is found in their own ingredients. As many readers will appreciate, you can play the same game with all sorts of other ingredients. Lactic acid (found in milk) is used in tanning leather. Palmitic acid, found in meats, coconut oil, sunflower seeds and many other foods, is used in making soap. 2,3-butanediol (a flavor component of many cheeses) is used in making printing ink and as antifreeze. I could go on all day; any organic chemist could. The entertainment value goes down after a while, because the fundamental premise (Good Healthy Natural Stuff versus Toxic Sludge) is stupid to start with.
So Panera, you’re playing on people’s lack of knowledge of chemistry in order to make yourselves look good. Your reasoning is faulty and your science is wrong. Your ads are offensive to anyone who actually understands chemistry, not that you care much, and you’re claiming a halo for yourselves that you don’t have. Do go on, though.
A randomized, double-blind, placebo-controlled trial published in Biological Psychiatry shows that sodium benzoate improves symptoms in clozapine-resistant schizophrenia
The common food preservative sodium benzoate improves symptoms in clozapine-resistant schizophrenia patients, according to a new study published in Biological Psychiatry. The randomized, double-blind, placebo-controlled trial led by Hsien-Yuan Lane, M.D., Ph.D., of China Medical University, Taiwan, showed that adding on sodium benzoate to the antipsychotic clozapine improved symptoms in patients who did not see results with any other medications, providing a new option for the hardest-to-treat patients.
"Clozapine is considered the last-line antipsychotic agent for patients with refractory schizophrenia," said Dr. Lane, referring to patients whose symptoms do not respond to available antipsychotics. But an estimated 40-70 percent of patients with refractory schizophrenia fail to improve even with clozapine, referred to as "clozapine-resistant," exhausting all potential options for treatment. The new study is the first to demonstrate that sodium benzoate-which has been shown to enhance other antipsychotic drugs-works in clozapine-resistant patients.
"If the finding can be confirmed, this approach may bring hope for treating patients with the most refractory schizophrenia," said Dr. Lane.
The 60 patients with schizophrenia included in the study were all taking clozapine, and received a placebo or sodium benzoate as an add-on treatment for six weeks. First author Chieh-Hsin Lin, M.D., Ph.D., of Chang Gung University College of Medicine, Taiwan, and colleagues tested two different doses of sodium benzoate (1 or 2 grams per day) to find which offered the biggest impact on symptoms with minimal side effects.
Compared with the placebo, sodium benzoate improved negative symptoms, such as lack of emotion and motivation, which have a greater influence on a patient's functional outcome than the more prominent psychotic symptoms. The higher dose of sodium benzoate also improved ratings of overall symptoms and quality of life. Although sodium benzoate has improved cognitive function when combined with other antipsychotics in previous studies, the add-on treatment had no influence on cognitive function in this study-in the paper, Dr. Lin and colleagues suggest that a higher dose or longer duration of treatment may be needed for these effects. Importantly, the patients taking sodium benzoate had no side effects, confirming the treatment is safe to use at the doses tested.
Sodium benzoate works by preventing the breakdown of D-serine, a brain chemical that plays an important role in signaling that is disrupted in the brains of people with schizophrenia. "Receptors for D-serine are long-standing targets for medication development in schizophrenia and sodium benzoate is probably the first meaningful tool that we have had to influence this target," said John Krystal, M.D., Editor of Biological Psychiatry. Although more studies are needed to learn how sodium benzoate enhances clozapine treatment in these patients, Dr. Krystal says that "this study highlights the importance for schizophrenia treatment of understanding the molecular switches that can be thrown to normalize brain circuit function."
Materials provided by Elsevier. Note: Content may be edited for style and length.
- Chieh-Hsin Lin, Ching-Hua Lin, Yue-Cune Chang, Yu-Jhen Huang, Po-Wei Chen, Hui-Ting Yang, Hsien-Yuan Lane. Sodium Benzoate, a D-amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial. Biological Psychiatry, 2017; DOI: 10.1016/j.biopsych.2017.12.006
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Elsevier. "Food preservative enhances schizophrenia treatment." ScienceDaily. ScienceDaily, 1 February 2018. <www.sciencedaily.com/releases/2018/02/180201092229.htm>.
Elsevier. (2018, February 1). Food preservative enhances schizophrenia treatment. ScienceDaily. Retrieved March 13, 2018 from www.sciencedaily.com/releases/2018/02/180201092229.htm
Elsevier. "Food preservative enhances schizophrenia treatment." ScienceDaily. www.sciencedaily.com/releases/2018/02/180201092229.htm (accessed March 13, 2018).