What is xanthan gum

Xanthan gum is a high-molecular-weight extracellular polysaccharide produced by fermentation process from bacterium species Xanthomonas campestris ¹. Xanthomonas campestris bacteria are single straight rods, Gram-negative, 0.4–0.7 μm wide and 0.7–1.8 μm long ². The fermentation medium contains sources of carbohydrate and nitrogen together with mineral salts. Once the fermentation process is complete, xanthan gum is recovered from the broth by ethanol or isopropanol precipitation in the form of a sodium, calcium or potassium salt. The resulting coagulum is separated, rinsed, pressed, dried and ground as part of downstream processing. Xanthan gum is marketed as a cream-coloured powder and is used as a thickener, stabilizer, emulsifier and foaming agent ³.

Xanthan gum is naturally gluten free.

The production and commercialization of xanthan gum as thickener and stabilizer has progressively increased at an annual rate of 5–10% ⁴, due to its better physicochemical properties as compared to other available polysaccharides. The most significant properties of xanthan gum include its high viscosity at low concentrations, xanthan gum viscosity in solution is nearly independent of pH and temperature, xantham gum ability to tolerate high concentration of electrolyte in solution and its stability for a wide range of temperatures and pH (even in the presence of salts) ⁵. Xanthan gum is biodegradable and biocompatible and forms gel in water. These properties have led to an increase in use of xanthan gum for  salad dressings, chocolate milk, bakery fillings, puddings and other foods to add texture ⁶. Xanthan gum is widely used in oral, peroral, and topical formulations as a suspending, thickening, emulsifying, or stabilizing agent ⁷. It has also been used as a controlled release agent in tablets, a binder in colon-specific drug delivery systems, and as a vehicle in ophthalmic liquid dosage forms ⁷, ⁸, ⁹. The global market for xanthan gum is ∼$500 million annually and continues to grow ¹⁰.

Figure 1. Xanthan gum (scanning electron microscopy)

Xanthan gum uses

Xanthan gum, 1%, can produce a significant increase in the viscosity of a liquid. Xanthan gum is currently permitted for use in a wide range of foods and beverages, with technical functions as an emulsifier, foaming agent, stabilizer or thickener. In foods, xanthan gum is common in salad dressings and sauces. It helps to prevent oil separation by stabilizing the emulsion, although it is not an emulsifier. Xanthan gum also helps suspend solid particles, such as spices. Xanthan gum helps create the desired texture in many ice creams. Toothpaste often contains xanthan gum as a binder to keep the product uniform. Xanthan gum also helps thicken commercial egg substitutes made from egg whites, to replace the fat and emulsifiers found in yolks. It is also a preferred method of thickening liquids for those with swallowing disorders, since it does not change the color or flavor of foods or beverages at typical use levels. In gluten-free baking xanthan gum is used to give the dough or batter the stickiness that would otherwise be achieved with gluten. In most foods, it is used at concentrations of 0.5% or less.

In cosmetics, xanthan gum is used to prepare water gels, usually in conjunction with bentonite clays. It is also used in oil-in-water emulsions to help stabilize the oil droplets against coalescence. It has some skin hydrating properties. Xanthan gum is a common ingredient in fake blood recipes, and in gunge/slime.

Is xanthan gum bad for you ?

A no-observed-adverse-effect-level (NOAEL) of 750 mg/kg body weight per day was established for xanthan gum in neonatal pigs, which are an appropriate animal model for the assessment of the safety of the additive for infants. The margin of exposure based on this no-observed-adverse-effect-level (NOAEL) and the conservative estimate of xanthan gum intake of 220 mg/kg body weight per day by infants (high energy requirements for fully formula-fed infants) is 3.4. On the basis of a number of considerations, the Joint FAO (Food and Agriculture Organization of the United Nations) and WHO (World Health Organization) Expert Committee on Food Additives (JECFA) concluded that the consumption of xanthan gum in infant formula or formula for special medical purposes intended for infants is of no safety concern at the maximum proposed use level of 1000 mg/L ¹¹.

Results of in vitro studies and studies involving oral administration of xanthan gum to rats show that xanthan gum is largely not digested by the enzymes in the upper gastrointestinal tract and is poorly absorbed ¹². Results of in vitro studies indicate that xanthan gum is susceptible to some microbial degradation in the lower gastrointestinal tract ¹³. Ingestion of xanthan gum by rats, dogs and human subjects was associated with variable changes in faecal and/or caecal short-chain fatty acid concentrations ¹⁴.

In short-term toxicity studies in animals, xanthan gum effects occurred mainly in the intestine at doses above 700 mg/kg body weight per day. These included faecal bulking and water binding, with some increases in intestinal tissue mass. At higher doses, reduced nutrient absorption was reported, which explained reduced weight gain and lower liver weights. Other organ weights were unchanged, and no gross morphological or histological abnormalities were reported. In dogs fed a diet containing xanthan gum for 12 weeks, stool softening was observed at doses above 250 mg/kg body weight per day, and occasional diarrhoea was seen at 1000 mg/kg body weight per day ¹⁵. Several new studies involving short-term dietary administration of xanthan gum to rats and dogs were identified. Edwards & Eastwood ¹⁶ reported increases in caecal tissue weight following feeding of xanthan gum in the diet at 5% (2500 mg/kg bw per day) for 4 weeks to male rats. Increased faecal output and increased faecal short-chain fatty acids were also reported in that study. In a 2-week study, Ikegami et al. ¹⁷ also noted heavier intestinal tissue weights, as well as small but significant increases in the length of the small and large intestines in rats fed 5% xanthan gum. Rats fed xanthan gum in the diet exhibited increased concentrations of total bile acids and volume of bile, as well as enhanced digestive enzyme activity; no effects on body weight gain were reported. In a 90-day study conducted with a new xanthan gum product in rats, the authors identified a NOAEL of 3301 mg/kg bw per day, the highest dose tested ¹⁸. In two additional studies of shorter duration (up to 10 days) involving dietary administration of xanthan gum (1.2% xanthan gum, equivalent to 300 mg/kg bw per day) to dogs, incorporation of the polysaccharide in the diet affected stool quality (i.e. increased moisture in the stools and softened stools) ¹⁹.

In long-term toxicity and carcinogenicity studies previously reviewed by the Committee, xanthan gum was reported to be well tolerated in rats and dogs at doses up to 1000 mg/kg bw per day provided in the diet for 2 years ²⁰. No increase in tumour incidence was observed ²⁰. In a three-generation reproductive toxicity study in rats [14], no adverse effects related to reproduction or in utero or postnatal development were reported when rats were given diets providing xanthan gum at doses up to 500 mg/kg bw per day.

In vitro studies on the effects of xanthan gum on the immune system have shown that xanthan gum induces DNA synthesis in mouse splenic B cells and thymocytes as well as polyclonal IgM and IgG antibody responses in B cells ²¹. Takeuchi et al. ²² described the production of interleukin 12 and tumour necrosis factor alpha following incubation of two murine macrophage cell lines with xanthan gum. They also reported that splenocytes obtained from xanthan gum–treated mice had greater natural killer cell activity compared with vehicle-treated mice. In addition, the investigators found that oral administration of xanthan gum inhibited transplanted tumour cell growth. These observations indicate biological activity of xanthan gum on exposed cells, but the relevance to humans is not known. In a study conducted in rats to specifically assess the potential effects of a number of fluid thickeners on absorption of water, no significant differences in the amount of water absorbed following treatment with xanthan gum–containing fluid (compared with pure water) were reported ²³.

Observations in humans

A series of studies involving full-term infants has been conducted to assess growth outcomes and tolerability as well as mineral absorption in infants fed xanthan gum in protein hydrolysate formula. When infants were fed reconstituted protein hydrolysate formula containing xanthan gum at concentrations up to 1500 mg/L (doses up to 232 mg/kg body weight per day) for 1 week, the xanthan gum–containing formula was better tolerated than the same formula without xanthan gum ²⁴. Relative to the hydrolysate formula without xanthan gum, infants fed formula with xanthan gum displayed decreases in the percentage of watery stools and in the number of stools per day.

In another study designed to determine the potential tolerability of formula differing in carbohydrate source, stabilizers and/or emulsifiers, infants were fed xanthan gum–containing formula (xanthan gum concentration 750 mg/L, dose 120–126 mg/kg bw per day) with or without OSA-modified starch for 20–28 days ²⁵. The growth outcomes (body weights and body weight gains) among the groups and mean rank stool consistencies were similar. Infants fed formula with xanthan gum passed significantly fewer stools per day compared with those fed formula without xanthan gum. The authors noted that there were no clinically relevant differences in serious adverse events between the treatment groups with and without xanthan gum, but that the presence of xanthan gum in the formula decreased vomiting. The highest dropout rate related to formula intolerance was reported in the group consuming formula without xanthan gum.

The overall conclusion regarding these two studies is that xanthan gum at concentrations of 750–1500 mg/L (doses 120–232 mg/kg bw per day) is well tolerated and does not affect growth characteristics.

In a study spanning up to 112 days, infants received either reconstituted protein hydrolysate formula with xanthan gum (750 mg/L; equivalent to 102 mg/kg bw per day) or an equivalent ready-to-feed formulation without xanthan gum ²⁶. Parameters evaluated in this study included body weight, food intake, growth outcomes (i.e. body weight gains, length and head circumference) and stool patterns. Feeding of xanthan gum–containing formula for up to 112 days did not adversely affect infant growth or development. The only statistically significant differences reported in this study were related to formula intake and stool production. Infants in the group receiving the ready-to-feed formula displayed greater intakes of the formula and passed more stools per day than did infants receiving the xanthan gum–containing formula. Additionally, parents of infants on the xanthan gum–containing formula responded more frequently that their babies were likely to pass less than one stool per day.

In two special studies (n= 6 or 22 infants) examining the potential effects of xanthan gum in formula on mineral absorption (750 and 1500 mg/L), slight decreases in mineral absorption were observed, which did not reach statistical significance ²⁷. Fractional calcium absorption was lower in the infants fed formula with xanthan gum, but net calcium absorption was similar to that of the infants fed non-xanthan gum–containing formula. With inclusion of xanthan gum in the protein hydrolysate formula, total zinc absorption and net zinc absorption were lower compared with the non-xanthan gum–containing formula. Despite the differences reported in mineral absorption in the studies, no effects on the growth of infants fed xanthan gum–containing formula were reported in these studies or in the 112-day infant growth study ²⁶. Post-market surveillance data collected by one manufacturer do not indicate any concerns related to growth of infants fed formula containing xanthan gum.

Cases of late-onset necrotizing enterocolitis in newborns (mostly premature) consuming breast milk or formula containing a xanthan gum–based thickener have been reported ²⁸. The concentrations of xanthan gum in these preparations were not reported. It is not possible to conclude, on the basis of available information, whether there is any causal association with intake of xanthan gum.

Post-marketing surveillance data were collected by one manufacturer over a 5-year period (June 2010 through May 2015) during which distribution of the hydrolysed powder containing xanthan gum (reconstituted at xanthan gum concentrations up to 1000 mg/L) and the ready-to-feed equivalent (without xanthan gum) equalled 105 million litres (providing exposure of a total of 131 million patient treatment days from the manufacturer’s products). The data show that consumption of formula containing xanthan gum is not associated with an increased rate of adverse events. The rate for any adverse event was less than one report per 10 000 patient treatment days. Overall, the post-market surveillance data provide additional support for the safe use of xanthan gum in infant formula, including specialized formula consumed by infants with protein allergy ²⁹.

Assessment of dietary exposure

The maximum proposed use level for xanthan gum in infant formula is 1000 mg/L. Infant formula consumption estimates were derived from mean estimated energy requirements for fully formula-fed infants. It should be noted that the energy requirements of formula-fed infants are greater than those of breastfed infants, although this disparity decreases with increasing age. A further exposure scenario was considered, using high (95th percentile) daily energy intakes reported for formula-fed infants. The highest reported 95th percentile energy intakes per kilogram body weight were for infants aged 14–27 days. For all dietary exposure estimates, a common energy density of formula of 67 kcal/100 mL (280 kJ/100 mL) was used to convert energy needs to the volume of formula ingested daily. Dietary exposure to xanthan gum from its use at the maximum proposed use level in infant formula ranges from 60 to 180 mg/kg body weight per day in infants aged 0–12 weeks, whereas infants with high (95th percentile) energy intakes may reach an exposure level of 220 mg/kg body weight per day.

Uses of xanthan gum in foods intended for infants and young children as listed in the General Standard for Food Additives (Codex Alimentarius Commission; UN Food and Agricultural Organization; Rome, Italy) or GSFA. are currently limited to complementary foods for these age groups ³⁰. The safety of xanthan gum for use in food was considered previously by the Joint FAO/WHO Expert Committee on Food Additives at its eighteenth, twenty-ninth and thirtieth meetings ³¹. At the thirtieth meeting, the Joint FAO/WHO Expert Committee on Food Additives established an Acceptable Daily Intake (ADI) “not specified”, on the basis of an absence of adverse effects in toxicological studies in rats and dogs supported by the absence of adverse effects in studies involving human subjects ³². At the present meeting, the Committee was asked to evaluate the safety of xanthan gum with respect to its proposed use as a thickener in protein hydrolysate infant formula, follow-on formula and formula for special medical purposes intended for infants (maximum proposed use level 1000 mg/L). The evaluation of the safety of xanthan gum for use as a thickener in formula considered the results of a number of unpublished study reports provided by the sponsor. In addition to the submitted data, a literature search was conducted. A consolidated monograph was prepared, which included studies from the previously published monograph, new study details from previously evaluated studies, new studies that had become available since the thirtieth meeting and older studies not previously reviewed by the Committee.

A NOAEL of 750 mg/kg bw per day (provided as a formulation of 1500 mg/L) was established for xanthan gum in neonatal pigs. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) considers that the neonatal pig is an appropriate animal model for the assessment of the safety of the additive for infants; the neonatal pigs are fed the xanthan gum–containing test formulations during the first 3 weeks of life (starting 2 days after birth) as the sole source of nutrition to model the 0- to 12-week period of development in human infants in which infant formula may be provided as the sole source of nutrition.

The margin of exposure (MOE) based on this NOAEL and the conservative estimate of xanthan gum intake of 220 mg/kg body weight per day by infants (high energy requirements for fully formula-fed infants) is 3.4. The Committee previously commented that when relevant uncertainties or conservatisms in the toxicological data and/or the exposure estimates were taken into account, an MOE in the region of 1–10 could be interpreted as indicating low risk for the health of 0- to 12-week-old infants consuming the food additive in infant formula ³³. The relevant considerations in relation to the evaluation of xanthan gum for use in infant formula are as follows:

• The toxicity of xanthan gum is low.
• The no-observed-adverse-effect-level (NOAEL) is derived from two studies in neonatal pigs, which are considered a relevant animal model for human infants.
• Clinical studies in infants support the tolerability of formula containing concentrations of xanthan gum up to 1500 mg/L.
• No adverse events were reported in post-marketing surveillance conducted by one manufacturer over a 5-year period on formulas containing xanthan gum at concentrations up to 1000 mg/L.

Based on these considerations, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) concluded that the consumption of xanthan gum in infant formula or formula for special medical purposes intended for infants is of no safety concern at the maximum proposed use level of 1000 mg/L, leading to the conservative estimate of dietary exposure of 220 mg/kg body weight per day. The Committee recognizes that there is variability in medical conditions among infants requiring formula for special medical purposes and that these infants would normally be under medical supervision ³⁴.

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