One Man's Food...

June 13, 2014

The Roman philosopher, Titus Lucretius Carus (c. 99 BC - c. 55 BC), wrote De Rerum Natura (On the Nature of Things), a didactic poem about physics.[1] It expounds the principles of atomism, and it argues that phenomena are cause by natural forces and not by the intervention of the gods.

Thomas Jefferson (1743-1826), who is arguably the most scientifically literate American president, had copies of this book in its original Latin and several translations in his huge personal library. Jefferson's library eventually became the Library of Congress, replacing the original library lost in the War of 1812. One memorable quotation from Lucretius' book is the following,

Ut quod ali cibus est aliis fuat acre venenum.
(What is food to one, is to others bitter poison)
- De Rerum Natura (On the Nature of Things), Book IV, l. 637

Our quality of life has been greatly enhanced by food additives, many of which retard spoilage and others of which enhance flavor. Most especially, people who choose to avoid too much sugar now have many options for sugar substitutes. You can avoid the "white" packets by using pink, blue, yellow, or green packets. The green packets are a recent innovation that didn't exist when I wrote about the chemistry of sugar substitutes in an early article (Pink/Blue/Yellow Packets, December 4, 2007).

The formerly predominant artificial sweetener, saccharin (C₇H₅NO₃S, 2H-1λ⁶,2-benzothiazol-1,1,3-trione), was discovered accidentally by Constantin Fahlberg of Johns Hopkins University in 1878. Artificial is a good term for it, since it was derived from coal tar. Pink packets, contain saccharin as its non-nutritive sweet component. It also contains dextrose and cream of tartar, the purpose of which is to reduce the bitter aftertaste of saccharin.[2] Pink packets have been available since 1957.

Calcium and sodium cyclamate (C₆H₁₂NNaO₃S, sodium N-cyclohexylsulfamate) is also used as a sugar-substitute in many countries, and it was used in the United States until 1969, when it was banned. The US ban was based on a study showing that intestinal bacteria can desulfonate cyclamate to form cyclohexylamine, a compound implicated in bladder cancer and testicular atrophy in mice. More than fifty countries allow the use of cyclamate as a food additive.

Aspartame (C₁₄H₁₈N₂O₅, N-(L-α-Aspartyl)-L-phenylalanine, 1-methyl ester), a methyl ester of aspartic acid and the dipeptide of phenylalanine, is the sweetening component of the blue packets, which contain dextrose and maltodextrin as aftertaste reducing components. One of the breakdown products of aspartame is phenylalanine, so it must be avoided by people with phenylketonuria.

The sweetening component of the yellow packets is sucralose (C₁₂H₁₉Cl₃O₈, 1,6-Dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside). Sold under the trade name, Splenda, sucralose is about twice as sweet as saccharin, four times as sweet as aspartame, and six hundred time sweeter than cane sugar (sucrose). Since its approval for use as a food additive in the US in 1998, Splenda has achieved predominance in the artificial sweetener market.

Fraternal twins. The sucralose molecule is sucrose with three hydrogen atoms replaced by chlorine. (Molecular structure diagram of sucrose (top, by Don A. Carlson), via Wikimedia Commons; bottom diagram of sucralose by NEUROtiker, via Wikimedia Commons. Note that some hydrogen atoms are omitted for clarity.)

Since sucralose is essentially sucrose for which three hydrogen atoms have been replaced by chlorine (see figure), it was marketed using the slogan, "Made from sugar, so it tastes like sugar." So, what did the competitors do when they saw their business eroded by such innovation? Hire more scientists? No, they claimed that Splenda was a chemical compound being sold as sugar, and they hired more lawyers. It all ended with an out-of-court settlement, and the box now in my cupboard simply states, "Tastes Like Sugar."

The pink, blue and yellow packets are artificial non-nutritive sweeteners, but there's been the recent entry of the green packet contender, the components of which are natural non-nutritive sweeteners. The green packets, sold under the trade name, Truvia, contain an extract of the Stevia rebaudiana plant, rebaudioside A, along with the simple sugar alcohol, erythritol (C₄H₁₀O₄, (2R,3S)-butane-1,2,3,4-tetraol).[3] Erythritol, which occurs naturally in some fruits, is an approved food additive in the US and many other countries.

Erythritol molecular structure. (Via Wikimedia Commons.)

School science fair projects are a good way to introduce students to the practice of science. I participated in many science fairs as a student, and I acted as a judge for several during my scientific career. Three years ago, Simon Kaschock-Marenda, a sixth grade student at the Julia R. Masterman School, a Philadelphia, PA, "magnet" school, needed a science fair topic. He decided that feeding non-nutritive sweeteners to fruit flies (Drosophila melanogaster) would be an interesting topic.[4]

Drosophila melanogaster (female, left, and male, right) (Via Wikimedia Commons.)

Simon's father, Daniel Marenda, is a biologist who works with fruit flies at Drexel University, so Simon had an accessible mentor. Simon found that fruit flies feed Truvia died in six days. Simon and his father repeated the experiment with better controls in a Drexel laboratory, and they got the same result. Further study showed that stevia wasn't the culprit; rather, it was erythritol. Since erythritol is recognized as safe for humans, there's the possibility that it can become the basis of a nontoxic pesticide.[4-5]

Drosophila melanogaster longevity on various sweeteners. (Fig. 1 of ref. 5, licensed under the Creative Commons Attribution License.[5])

Now, three years later, the results of a careful study have been published in the journal, PLOS One.[5] Among the coauthors are Simon, now 14 and in the ninth grade, and his father. Drexel has applied for a patent on using erythritol as an insecticide with a hope that it will also prove effective against Drosophila suzukii, a newly invasive species in the US.[4]

Although the effect has been clearly demonstrated, it's not known how erythritol kills fruit flies, although fruit flies eating erythritol showed impaired motor coordination.[4-5] Another sugar alcohol, mannose, is toxic to honey bees, but not fruit flies.[5] One interesting note, Simon didn't win a prize in his sixth grade science fair.[4] That's probably good training for reaction to peer review in later life.

References:

1. Titus Lucretius Carus, "De rerum natura," J. D. Duff, Ed., Cambridge : The University Press, 1930; Titus Lucretius Carus, "Of The Nature of Things," William Ellery Leonard, Tr. (via Project Gutenberg).
2. Marvin E. Eisenstadt, "Cyclamate-free artificial sweetener," US Patent No. 3,625,711, December 7, 1971.
3. Steven J. Catani, "Erythritol-containing tabletop sweeteners and methods of producing same," US Patent Application No. 12/147,075, Publication No. 20090004355, Priority Date, June 29, 2007. Also published as CA2691547A1, EP2173191A1, and WO2009006200A1.
4. Tom Avril, "Boy scientist in Manayunk finds sweetener that kills fruit flies," philly.com, June 5, 2014.
5. Kaitlin M. Baudier, Simon D. Kaschock-Marenda, Nirali Patel, Katherine L. Diangelus, Sean O'Donnell and Daniel R. Marenda, "Erythritol, a Non-Nutritive Sugar Alcohol Sweetener and the Main Component of Truvia®, Is a Palatable Ingested Insecticide," PLoS ONE, vol. 9, no. 6 (June 4, 2014), Document No. e98949, doi:10.1371/journal.pone.0098949. This is an open access article, available as a PDF file, here.