Recently, I listened to an interview (from 2015) of a scientist who did a study on emulsifiers and found that they can lead to low-grade inflammation in the gut, especially in mice with certain immune system genes knocked out. I find the interaction between our genes and our microbiome to be fascinating.
Last summer I did a whole series of posts about various genes associated with obesity. In the end, I came to understand some of the genetic contributions to weight gain and metabolic syndrome, but I knew that I was still missing a huge piece of the puzzle.
I knew that the gut microbiome played a big role, but every time I started a blog post about it, those puzzle pieces seemed to go in different directions.
Our genes and our environment both contribute to our gut microbiome, allowing some species to flourish and keeping others away. How does this all come together to cause the diseases that plague our modern society?
Just a warning — this is a long post! I’ll outline my thinking, add in lots of studies, and get to the genetic component towards the end.
Why do we gain weight?
Let’s get to the heart of a huge topic and look at some elements involved in either being overweight/obese and having metabolic syndrome:
- Low-grade, chronic inflammation
- A gut microbiome component (scientists can create fat mice with fecal transplant from obese mice into germ-free, normal weight mice)
- On the rise since the 1970’s (graph)
- Calories in/calories out isn’t the whole picture (graph of last 10 years show stable calories, yet obesity/metabolic syndrome is still rising)
Diets that cause weight loss (at least initially):
There seems to be a new diet craze every few years. Paleo and ketogenic diets seem to be “in” right now. Fanatics of any diet will be happy to tell you how wonderful each one is, but we still seem to have problems with obesity and related health problems.
So what is the common element in these diets?
- the ketogenic diet (avoids carbs and most packaged foods)
- paleo diet (avoids most carbs and thus packaged foods)
- raw vegan diet (avoids packaged foods)
- fruitarian diet (avoids fat and packaged foods)
- Ornish diet “Eat Mostly Plants in their Natural Form” (avoids packaged foods)
- Mediterranean diet (focuses on fresh food instead of packaged foods)
The common thread seems to be avoiding packaged foods. What do packaged, processed foods have in common? Emulsifiers.
What are emulsifiers?
Emulsifiers help solve the age-old problem of getting water and oil to mix. Consisting of a water-loving and oil-loving end, emulsifiers are molecules that are attracted to both oil and water. Egg yolks are an example of a natural emulsifier.
Some of the first emulsifiers patented for use in foods were a derivative of fatty acids called mono- and diglycerides. Several patents from the 1930’s show mono- and diglycerides being used for shortening. Cottonseed oil was cheap and abundant and became the oil of choice in shortening, used instead of lard in baking bread, cakes, and cookies. These days emulsifiers are used in most baked goods, ice cream, some deli meats, pickled products, salad dressings, sauces, coffee creamer, etc. to make food shelf stable with a good texture.
Emulsifiers can also act as surfactants, which reduce surface tension. Surfactants are commonly found in detergents – think about a drop of dish detergent breaking up the grease in a pan.
carboxymethylcellulose (CMC or cellulose gum, GRAS and can be up to 2% in various foods)
“CMC is used in food under the E number E466 as a viscosity modifier or thickener, and to stabilize emulsions in various products including ice cream. It is also a constituent of many non-food products, such as toothpaste, laxatives, diet pills, water-based paints, detergents, textile sizing, and various paper products. It is used primarily because it has high viscosity, is nontoxic, and is generally considered to be hypoallergenic as the major source fiber is either softwood pulp or cotton linter. CMC is used extensively in gluten free and reduced fat food products.” Wikipedia
polysorbate-80 (P80 or Tween 80, up to 1% in certain foods, usually less than 1%)
Polysorbate 80 is a surfactant and emulsifier used in foods and cosmetics. Ice cream often includes polysorbate 80 (up to 0.5%) to help it stay smooth. Anyone who has made homemade ice cream knows that it is hard to keep in the freezer for long without the texture changing. It is also found in a lot of pickles and pickled products. The acceptable daily intake (World Health Organization) is 25 mg/kg body weight/day, acute toxicity is low, and it is not considered cancer causing.
So why would things that are pretty much non-toxic and allowed to be added to our foods even be a problem? Let me get to the heart – or rather gut! – of the matter.
A little background on the gut:
The intestinal wall is lined with epithelial cells with a mucosal barrier to keep out microbes and to protect against digestive enzymes. The microbes in our guts perform a variety of functions for us, including making some vitamins and short-chain fatty acids.
So why is it so important to have a good intestinal mucosal barrier? While it sounds a little icky, the mucosal barrier keeps microbe away from the epithelial cells and thus out of the body’s circulation. When the mucosal barrier is disrupted, the immune system gets activated by gut microbes, thus causing an inflammatory response. This can lead to autoimmune and inflammatory conditions such as food intolerances, IBD, and diabetes.
So if a dysfunctional mucosal barrier can cause intestinal and autoimmune disorders, what does a thinner than normal barrier do? According to a scientist at Georgia State University, it causes low-level inflammation, which could be driving weight gain and metabolic syndrome.
Current Studies of Emulsifiers and the Gut Microbiome
There have been studies in the past (Studies 1, 2, 3) that have investigated the toxicity and cancer-causing properties of carboxymethyl cellulose, hydroxypropyl methylcellulose, and polysorbate 80. These emulsifiers were found to be acceptable for use as food additives (Studies 1, 2, 3). But several new studies within the last couple of years have been looking at the chronic, low dose effect on the intestines, which paints a new picture of the health effects of the emulsifiers.
Studies on chronic effects of emulsifiers/surfactants:
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome – Nature, 2015 (Abbreviations: WT = wild-type, CMC = carboxymethyl cellulose, P80 = polysorbate 80)
“Metabolic syndrome is associated with, and may be promoted by, low-grade inflammation 26, Thus, we examined whether emulsifier-induced microbial dysbiosis and low-grade inflammation might promote this disorder in WT mice. Both CMC and P80 resulted in modest but significant gains in overall weight and a marked increase in adiposity as measured by fat mass (Fig. 3A-B). Such increased adiposity was associated with increased food consumption (Fig. 3C) that likely drove the increased adiposity. Emulsifier treatment also impaired glycemic control as assessed by fasting blood glucose concentration (Fig. 3D) and glucose/insulin tolerance testing (Fig. S7B).”
“we next sought to better define the minimum doses of emulsifiers that would produce evidence of low-grade inflammation/metabolic syndrome. As little as 0.1% CMC resulted in modest increases in body weight and fasting glucose while 0.5% resulted in clear evidence of low-grade inflammation (shortened colon, enlarged spleen) and increased adiposity”
“For P80, as little as 0.1% resulted in evidence of low-grade inflammation and increased adiposity, while 0.5% resulted in mild dysglycemia (Fig. 3K-L and S7D). Emulsifier-induced metabolic syndrome was also observed in older mice (Fig. S5A) and persisted for at least 6 weeks after stopping emulsifier consumption”
I encourage you to read the whole study — it is actually fairly easy to understand! The study seems to be well done: it addresses many of the drawbacks of previous mice studies; dosages used are similar to what a lot of people in the US eat on a daily basis; it was a long-term study; the authors have a solid background in the field; it was funded by NIH with no conflicts of interest.
To sum up, the emulsifiers used in this study caused bacteria to be located closer to the epithelial cells of the intestine. For mice that were genetically susceptible to colitis, this caused colitis. For normal mice, this caused low-grade inflammation, fat gain, and mild blood sugar level issues.
Another study showing the effects of polysorbate 80 on the mucosa: Food Additive P-80 Impacts Mouse Gut Microbiota Promoting Intestinal Inflammation, Obesity and Liver Dysfunction
“Compared with control mice, those receiving emulsifier, showed impaired glycemic tolerance, hyperinsulinemia, altered liver enzymes, larger mitochondria and increased gall bladder size. Additionally, mice in the experimental group showed higher levels of DCA, reduced Muc2 RNA expression, reduced mucus thickness in the intestinal epithelium and increased gut permeability. Intestinal bacteria of mice receiving P-80 were found deeper in the mucus and closer to the intestinal epithelium and had increased level of bioactive LPS, flagellin and LCN2 expression. The result of the study are supportive of evidence that emulsifier agents such as polysorbate-80, may be contributing to obesity related intestinal inflammation and progression of liver dysfunction and alternation of gut microbiota.”
“Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer.”
This study looked at the effect of non-starch polysaccharides and food emulsifiers on the ability of E. coli to cross M-cells, which are the cells in the mucosa in the intestinal tract. The study found that while plant fibers, such as broccoli and plantain, reduced E. coli translocation across M-cells, the addition of polysorbate 80 at 0.01% vol/vol increased E. coli translocation by 59x.
Polysorbate 80 (Tween 80) is commonly used in labs as an emulsifier. This study looked at the effect of Tween 80 on the growth of bacteria and found that it inhibits certain bacteria and promotes others. Effects of Tween 80 on Growth and Biofilm Formation in Laboratory Media
“As Tween 80 is a commonly used emulsifier both in research and industries, the effects shown in this study call for re-evaluation of its use. It should be used with care in bacterial assays since it has strain-specific effects on planktonic and biofilm growth. The greatest effect was seen for the lowest concentration used in this study, 0.1%. The effects might be even greater at lower concentrations. This should be investigated further in the future. In this study, the emulsifier was shown to promote both planktonic and biofilm growth of S. aureus, whereas it inhibited L. monocytogenes and P. fluorescens. … Tween 80 is added to a wide range of foods, pharmaceuticals and cosmetics. A cream containing Tween 80 could affect the skin bacteria and foods and pharmaceuticals with Tween 80 could affect the gut microbiota.”
“Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods, which alter the composition of gut microbiota. Here, we demonstrate in a preclinical model of colitis-induced colorectal cancer that regular consumption of dietary emulsifiers, carboxymethylcellulose or polysorbate-80, exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development.”
Genes involved in immunity:
The first study above that looked at the impact of emulsifiers on the mucosal barrier broke out the mice into wild-type, IL10 knockout, and TLR5 knockout. In humans, IL10 and TLR5 genetic variants have been correlated with higher risk of inflammatory bowel diseases. NOD2 is another gene in which variants increase the risk of inflammatory bowel diseases. These genes are all involved in immune system function.
IL10 is the gene that codes for interleukin 10, an anti-inflammatory cytokine. It prevents the immune system from reacting too strongly or inappropriately. It has been known for more than 20 years that “In the absence of IL-10, spontaneous mucosal autoimmunity develops, while the effect on systemic autoimmunity is far more muted”. [ref]
- rs1800896 (C is the risk allele in the 23andMe orientation; also referred to as -1082A>G)
- rs1800871 (G is the risk allele in the 23andme orientation; also referred to as -819T>C)
- rs1800872 (G is the risk allele in 23andme orientation; also referred to as -592A>C)
- rs3024505 (A is the risk allele in 23andMe orientation)
NOD2 polymorphisms are a risk factor for Crohn’s Disease. The variants lead a defective inflammatory response in the intestinal wall. Studies (above and here) show that the emulsifier polysorbate 80 increases adherent invasive E. coli, which increases inflammation and the risk for Crohn’s Disease.
- rs2066844 – The T allele is strongly linked to Crohn’s disease with heterozygous (CT) having a 3x risk and homozygous (TT) having a 35x risk. [ref]
- rs2066845 – The C allele is strongly linked to Crohn’s disease with heterozygous (CG) having a 3x risk and homozygous (CC) having a 35x risk. [ref]
- rs2066847 – The insertion (I) is strongly linked to Crohn’s disease with heterozygous (DI) having a 3x risk and homozygous (II) having a 35x risk. [ref]
- rs17221417 – The G allele is somewhat linked to Crohn’s disease with heterozygous (CG) having a 1.3x risk and homozygous (GG) having a 1.9x risk. [ref]
Is it even possible to avoid emulsifiers in foods? Sure. But it will be labor intensive and inconvenient. Eating becomes nearly impossible, and a trip to the grocery store means time spent reading all the labels.
Would it be worth it? I think so. I’m planning to cook most meals at home and check ingredients lists before eating out at restaurants. The biggest source of methylcellulose in my cabinet seems to be in supplements. Most capsules are made of cellulose instead of gelatin these days, and quite a few tablets include either CMC or polysorbate 80.
A few final thoughts…
When looking into emulsifiers and their effect on our gut, I noticed several things along the way. None of these observations are probably unique, but I wanted to point them out.
Control mice are being fed emulsifiers
It turns out the ‘control’ group for some weight-related studies in mice are fed CMC or another emulsifier as the control. This makes it hard to know if the substance being tested is reducing adiposity or if the ‘control’ which was fed cellulose is gaining weight due to the emulsifier. (Study 1, 2)
The pharmaceutical industry uses many of the same food grade emulsifiers to enhance the bioavailability of their drugs. The mucosal intestinal barrier is something that drugs must overcome, and adding in emulsifiers increases their bioavailability. [ref] There are quite a few pharmaceutical studies available on increased absorption due to the use of emulsifiers.(Studies 1, 2, 3, 4, 5) Apparently, the pharmaceutical industry has known for many, many years that including a surfactant/emulsifier along with the drug increases the absorption in the gut through reducing the mucosal barrier. Quite a few of the most common prescription medicines contain polysorbate 80, carboxymethylcellulose w/ sodium, and methylcellulose. (Note that I’m not encouraging anyone to stop taking a prescription medication just because it contains an emulsifier! Always talk with your doc.)
I want to end this both with an article that seems to confirm my thinking and a list of what I still need to find out more about.
A Seattle Children’s Hospital gastroenterologist published a paper showing that he was able to cure Crohn’s disease and ulcerative colitis using a diet that removed “grains, dairy, processed foods and sugars, except for honey”. The diet only included vegetables, fruits, meats, and nuts — which would thus eliminate emulsifiers completely.
There is a lot that I don’t yet know. While polysorbate 80 and carboxymethylcellulose seem to be fairly well linked to intestinal mucosa disruption, I do not yet know about other specific emulsifiers/surfactants in our foods. These would include mono- and diglycerides, xanthan gum, carrageenan, soy lecithin, ammonium phosphatide, a whole host of gums, and a bunch of other chemicals that I can neither pronounce nor spell. I also need to further look into the actions of surfactants vs. emulsifiers since not all emulsifiers are surfactants.
More to read: