Sunday, November 25, 2012

John L. Holahan—SimplyThick—Xanthan Gum—Necrotizing Enterocolitis

Xanthan gum, a biotechnology product, was invented by the research team of Allene Rosalind Jeanes of the United States Department of Agriculture. This polysaccharide was approved as a food additive in 1968.

is produced by X. campestris, a plant-associated bacterium that is generally pathogenic for plants belonging to the family Brassicaceae. Xanthomonas causes a variety of disease symptoms such as necrosis, gummosis and vascular parenchymatous diseases on leaves, stems or fruits; an example is "black rot" of crucifers such as cabbage, cauliflower or broccoli. Xanthomonas does not form spores, but it is very resistant to desiccation during relatively long periods. Survival at room temperature for 25 years has been reported by Leach et al.(1957).
Xanthan gum has numerous profitable applications but did not enter the marketplace as an infant formula thickening additive (SimplyThick®) until recently. The FDA is investigating whether the SimplyThick product is linked to the multi-hospital and at home necrotizing enterocolitis events. It is curious to note that the xanthomonas bacterium causes necrotic plant disease.

John L. Holahan, SimplyThick president, advertises his product as an aid for people suffering from dysphagia, (difficulty swallowing) not for infants exhibiting reflux symptoms. Xanthan gum, the preferred base for SimplyThick®, is proposed as a bulking agent in breast milk according to the patent (2009) filed by Mr. Holahan.

In 2001, Mr. Holahan paid the Burdock Group for its expert opinion regarding SimplyThick/xanthan gum efficacy and safety. George A. Burdock, PhD  and Ioana G. Carabin, MD relying on one, xanthan gum, clinical adult trial advised their client to initiate marketing.

The Burdock referenced supportive study:  "The dietary effects of xanthan gum in Man" by researchers: Eastwood, Brydon, and Anderson — Food Additives and Contaminates 1987 Vol. 4 No. 1, 17-26. — determined that the test xanthan product, Keltrol T, "does not appear, therefore, to cause any adverse toxicological effects."  This often-cited work was financed by U.S. xanthan gum manufacturer Kelco, Inc.

The European Food Safety Authority in 2011 classified the Eastwood et al. uncontrolled xanthan gum study findings inconclusive.

On September 2012 the FDA issued a SimplyThick alert and warned that the use of the xanthan-gum based product could cause life-threatening injuries to pre and post term infants. In this advisory, the agency reported that 7 infants had died and many others had developed necrotizing enterocolitis (NEC) after being prescribed SimplyThick. The previous, May 2011, FDA communication advised that the SimplyThick product posed a health risk to premature infants.

Texas Children's Hospital— February 2012
External thickening agents, including Simply Thick, Thick It, and several other similar products should not be used under any circumstances for any infants < 44 week postmenstrual age *(gestational age plus chronological age). At present the cases of NEC and similar illnesses are limited to those born < 37 weeks who developed illness at < 43 weeks PMA. This puts a small boundary around it.
SimplyThick®/necrotizing enterocolitis incidents have been reported in the following states:

New York (May, '10)
North Carolina (April, '11)
New Mexico (September '09) A New Mexico hospital reported eleven cluster NEC cases in early 2007, etiology unknown.
Colorado (May, '09)
Texas (May, '11)
Indiana (January, '10)
Florida (April, '11)

Canadian health authorities have also established a relationship between SimplyThick® and NEC.

One of the most relevant NEC cases involve Florida twins, Jaden and Genesis Santos, who were under Florida Hospital Neonatal care in 2011. Shortly after discharge and on a medically prescribed SimplyThick® feeding regime, Jaden Santos died of necrotizing enterocolitis on April 8, 2011. For additional information on this issue please link to SimplyThick Neonatal Intensive Care Practices.

Those researching the SimplyThick® product for a causal link to necrotizing enterocolitis will find the issue complex.

SimplyThick Manufacturing Deficiencies &Product Contamination

The FDA determined during its June 2011 inspection that one of three SimplyThick processors was not following safe manufacturing practices. Bacillus cereus contaminated one raw xanthan gum sample and was found in finished SimplyThick packets. As a result of the FDA findings, SimplyThick products manufactured by Thermo-Pac, June 1, 2009-June 3, 2011, were recalled. For additional information please link to Thermo Pac, LLC—SimplyThick— Processing Deficiencies.

Infant Formula Thickening Agents Medically Questionable

A number of researchers and practitioners believe that SimplyThick and other thickeners are not suitable for infants. "Infants are not meant to be eating
solid foods, so these products are not appropriate," states Jesse Reeves-Garcia, MD, director of gastroenterology, Miami General Hospital.

Material Injury

At this juncture, the FDA has not determined whether SimplyThick/xanthan gum, thickening agents, or unsafe manufacturing practices are responsible for the infant NEC fatalities and illnesses.

While the FDA seeks a NEC cause, CP Kelco, the largest domestic producer of xanthan gum, is claiming material injury as a result of anti-dumping practices on the part of China and Austria.

U.S. International Trade Commission Xanthan Gum Findings July 2012

Xanthan gum is a polysaccharide produced by the fermentation of a carbohydrate source using the strain of bacteria known as Xanthmonas capestris. Xanthan gum is sold in the form of a milled, granular powder and in a variety of grades. Due to its unique molecular structure, it is a naturally-derived stabilizer of water-based solutions that is used primarily for its thickening, stabilizing, and suspension properties in a wide variety of products and industries.

Physical Characteristics and End Uses.

All grades of xanthan gum are derived from fermentation of the bacteria Xanthomonas campestris and, as such, each grade shares the same basic physical characteristics and chemical composition. The different grades of xanthan gum primarily are used for a variety of purposes in three end-use industries: food and beverage, oil and industrial applications, and consumer applications (e.g., cosmetics and pharmaceutical products). The various grades differ somewhat in terms of purity level or grain size according to the specific needs of purchasers or specific regulatory standards for the end-use application. The various grades of xanthan gum used in the three major end-use applications generally serve as thickening or stabilizing agents.

Channels of Distribution.

The different grades of xanthan gum are generally sold in the same channels of distribution, with most xanthan gum being sold directly to end-users and the remainder to distributors.

Manufacturing Facilities, Production Processes, and Employees

All xanthan gum is made in similar manufacturing facilities, using similar production processes and employees. The production process for xanthan gum may vary slightly depending on the grade being produced, such as one requiring additional enzymes or a different particle size. Additionally, government regulations require that the manufacture of food grade xanthan gum occur in an environment designed to limit microbiological contamination. Nevertheless, all xanthan gum products can produced on the same production lines that are GMP (good manufacturing processes) because these lines satisfy the necessary quality control requirements.

Producer and Customer Perceptions.

The limited evidence in this preliminary phase indicates that all grades of xanthan gum are perceived by both producers and customers to be the same product, although certain food and consumer product grades must meet the necessary regulatory requirements.


The record indicates that prices vary among the end-use industries. Food grades and consumer grades are required to be free from microbacterial contamination. As such, these grades are generally higher priced than oil grades. Xanthan gum is manufactured in only four countries, the United States, Austria, China, and France, all of which export xanthan gum. Xanthan gum is produced from the fermentation of the bacteria strain Xanthomonas campestris. The production process requires maintaining the bacteria strain used for culture; providing carbohydrate, nitrogen, and micronutrient sources to initiate the fermentation process; extracting and refining the xanthan gum from the culture; milling the product into a powder; and finally packaging it for distribution. The production process begins with fermentation of the bacteria. First, selected strains of Xanthomonas capestris must be properly maintained and stored for continuous production. A small amount of the strain is expanded in a shake flask, and then further reproduced in a seed tank for scalable expansion, to create the inoculum for large bioreactors. Next it is placed in a bioreactor where it interacts with a carbohydrate source (typically a corn derivative, such as corn starch), a nitrogen source (such as casein hydrolysates, soybean meal, or distillers’ solubles), micro-minerals, and water. At the end of this step xanthan gum broth is produced, which contains xanthan, bacterial cells, and other chemicals. Recovery of the xanthan gum begins by removing the cell debris using either filtration or centrifugation. Next alcohol (such as isopropanol, ethanol, or acetone) is added to broth to separate the xanthan gum from water, creating a xanthan gum fiber. The resulting residual mixture of alcohol, water, cellular debris, and nutrients is distilled to recover the alcohol; while the other residual material is sent to a water waste treatment facility. The xanthan gum fiber is then dried, milled to a particular granule size, and packaged into specified quantities. The product may also be coated with non-water soluble material, such as cottonseed oil or lecithin, to aid in the dispersal of the xanthan gum particles when placed in a solution. At this point, the xanthan gum is marketable. Xanthan gum production requires that facilities meet standards set by the Environmental Protection Agency for wastewater. For industrial grade xanthan gum, this is the main regulatory concern with the production process. In order for xanthan gum to qualify as “food grade,” the FDA requires certain processes and tests be done, as does the USDA for certain meat and dairy products. First, the FDA requires that the strain of Xanthomonas capestris be nonpathogenic and nontoxic to humans and animals. Second, it requires that the recovery process renders no viable cells of the strain. There are also specifications that the residual isopropyl used in the recovery process must not exceed 750 parts per million; the final product must meet certain viscosity properties; the product must also pass two specified laboratory tests; and finally, the product must have proper labeling and use information. Several importers provided additional comments on the comparisons. *** stated that xanthan gum is a complex product, and even if two suppliers offer the same specification, it might happen that one xanthan gum works in a specific application, and the other does not. *** stated that the quality of the imported product from China has always been inferior to the U.S.-produced product, a problem that is a concern to domestic food manufacturers.