How carrageenan affects insulin resistance

New research links carrageenan, a popular food additive, to heightened inflammation and insulin resistance in overweight individuals, raising concerns over its widespread use in processed foods.

Study: Carrageenan and insulin resistance in humans: a randomised double-blind crossover trial. Image Credit: Plataresca / Shutterstock.com

A recent study published in the journal BMC Medicine examines the effects of carrageenan on human health.

What is carrageenan?

The Western diet is often high in fat, carbohydrates, and ultra-processed foods, the latter of which are high in saturated fatty acids and low in diet fiber. Consumption of these food products can increase the risk of type 2 diabetes mellitus (T2DM) and obesity.

Carrageenan, extracted from red seaweed, is a commonly used additive consisting of modified galactose units. Its ability to form hydrocolloids and gels allows this additive to improve the texture of various dairy foods, including ice cream and milk-based drinks, as well as meat products like sausages.

Previous in vivo studies have reported that the breakdown products of carrageenan, including polygeenans, are associated with adverse effects, including inflammation, as well as an increased risk of gastrointestinal ulceration and cancers. Furthermore, carrageenan exposure has been shown to increase the risk of glucose intolerance and worsen hyperglycemia in individuals consuming a high-fat diet.

In the 1970s, daily intake of carrageenan was about 45 mg/day; however, current estimates indicate that many individuals consume over 250 mg/day of carrageenan. Thus, the rising use of carrageenan in the food supply, combined with mixed observations on the potential adverse effects of exposure to this food additive, necessitates additional studies to clarify its impact on human health.

About the study

The current study was a double-blinded, randomized controlled trial (RCT) conducted at a single center. It involved 20 males with a mean age of 27.4 years. None of the study participants had a history of metabolic syndrome at baseline.

The crossover design involved a dose of 250 mg carrageenan or placebo provided twice every day for two weeks, after which the two arms crossed over. Study participants were tested for insulin sensitivity by an oral glucose tolerance test (OGTT), whereas a hyperinsulinemic-euglycemic clamp was used to measure skeletal muscle insulin sensitivity.

Liver insulin sensitivity, inflammation, and insulin resistance in the brain, gut permeability testing, and gut microbiome composition were assessed. Peripheral blood markers indicating immunologic activation were also measured.

No difference in insulin sensitivity

During the trial, both carrageenan and placebo treatment were associated with similar whole-body, hepatic, brain, and skeletal muscle insulin sensitivity. Interleukin 13 (IL-13) levels were raised in response to tetanus toxoid in the carrageenan treatment group; however, no impact on other pro-inflammatory markers, including C-reactive protein (CRP), IL-6, IL-17, or immunoglobulin antibodies, was observed. Likewise, no significant alterations in the composition of the gut microbiome were reported.

Zonulin levels were raised following carrageenan intake. Zonulin is a protein produced by intestinal epithelial cells. It reduces tight junction proteins, which results in T-cell-mediated inflammation of the gut mucosa, and regulates the traffic of immune cells from the gut to the rest of the body. Loss of tight junctions in the gut epithelium is associated with epithelial injury, leaky gut, and bacteremia.

The lack of a change in insulin sensitivity could be due to the relatively short exposure period, with insulin sensitivity regulated by complex interactions between multiple organs. Furthermore, the baseline healthy status of the study participants, none of whom were obese, may also be a confounding factor.

Body weight affects outcomes

These observations were modified when analyzed for interactions with the participant’s body mass index (BMI). Indeed, whole-body insulin sensitivity was lower after carrageenan intake among overweight participants, along with increased insulin resistance. As BMI rose, hepatic insulin sensitivity was often reduced, whereas brain inflammation was more likely to increase.

Skeletal muscle insulin sensitivity did not change in relation to BMI. This finding is supported by previous studies demonstrating that gut inflammation mediates altered insulin sensitivity of the liver and brain rather than that of skeletal muscle. Inflammatory markers like C-reactive protein (CRP) and IL-6 were also raised alongside increased gut permeability.

Immune cell activation by carrageenan

When isolated peripheral blood mononuclear cells (PBMC) were exposed to carrageenan in vitro prior to carrageenan treatment, natural killer (NK) cells were activated, along with the release of various cytokines, including IL-6, IL-13, IL-17, tumor necrosis factor-β (TNF- β), and granulocyte-monocyte colony stimulating factor (GMCSF).

Conclusions

Despite being classified as a generally regarded as safe (GRAS) substance, carrageenan consumption appears to cause insulin resistance by inducing subclinical inflammation among overweight individuals, with this effect mediated by pro-inflammatory changes in the gut. In the presence of obesity and, possibly, gut dysbiosis, carrageenan may cause intestinal epithelial barrier injury, thereby promoting systemic inflammation and leading to overt insulin resistance.

Previous animal studies conducted in rodents and non-human primates have demonstrated intact survival with long-term carrageenan intake. However, at high doses, carrageenan exposure caused inflammation of the gut in primates and humans. The increased gut permeability observed in the current study did not induce any gastrointestinal symptoms, thus indicating that carrageenan-related toxicity may be asymptomatic for a significant duration. 

Future studies are needed to elucidate the effects of consuming carrageenan and other food additives in a high-risk population and over longer durations.

The results warrant caution with carrageenan-containing foods, especially in individuals who are prone to develop type 2 diabetes.”