You might see mannitol as an ingredient in zero, low-calorie, or sugar-free foods such as chewing gum, energy bars, ice cream, pudding, frosting, cakes, cookies, candies, and jams. In addition to being a highly used sugar substitute, mannitol is on the WHO Essential Medicine List (EML) and is used clinically as an osmolyte (used in regulating fluid pressure) to help relieve brain and eye swelling, and to protect kidney function during surgery by inducing increased urination or diuresis.
But the potential benefits of a mannitol supplement aren’t limited to just these uses. Come along as we explore the scope of mannitol as a dietary supplement, its potential as a prebiotic and subsequent health benefits, and the role it might play in maintaining the integrity of a healthy gut.
Mannitol - What is it and how is it made?
Mannitol is found abundantly in nature in plants and fungi as it helps regulate fluid balance and acts as a ROS (reactive oxygen species) scavenger. It is a six-carbon sugar alcohol - a complex carbohydrate that contains subunits of sugar (mannose) and alcohol molecules - naturally found in small amounts in vegetables such as mushrooms, cauliflower, asparagus, etc.
Commercially, mannitol powder is used as a nutritive sweetener in confectionaries such as candy, chewing gum, and chocolate coatings, as the base for chewable tablets, and in specialized diabetic foods.
Mannitol powder is made using different methods such as plant extraction, chemical hydrogenation of fructose, or by using microbial fermentation using lactic acid bacteria (LAB) from the Lactobacillus, Leuconostoc genera, etc., that can convert a mix of glucose and fructose molecules into mannitol.
Learning about mannitol and digging into the research was a pivotal moment leading up to the development of our Sugar Shift probiotic, as I share more about it in this blog post.
Sugar, mannitol, other sugar alcohols, and artificial sweeteners - What’s the difference?
Sweeteners are differentiated as nutritive or non-nutritive depending on their caloric value. Both sugar and sugar alcohols fall under the umbrella of nutritive sugars/sweeteners while artificial sweeteners are non-nutritive sugars.
Difference in table sugar and mannitol
Sugar alcohols (or polyols) are not the same as sugar (sucrose or fructose) as they differ in molecular structure, calories, sweetness, or digestibility. Sugar has a high glycemic index (GI), contains 4 calories per gram (kcal/g), and quickly reaches the bloodstream raising blood sugar levels.
Mannitol is structurally and functionally different from sugar. White or table sugar is sucrose, a disaccharide (mix of two monosaccharides - glucose and fructose) that has the molecular formula, C ₁₂H ₂₂O ₁₁, and contains only roughly 4kcal/g.
Mannitol, on the other hand, is a derivative of the monosaccharide, mannose. It has the molecular formula, C6H14O6, contains roughly 1.6 kcal/g, has a zero glycemic index score (due to low absorption), and tastes only half as sweet as sugar.
Mannitol in the gut and the veins
Ingested (eaten) mannitol that stays within the gastrointestinal tract acts differently from mannitol in the bloodstream, applied via IV in clinical situations. When you ingest mannitol, very little mannitol gets absorbed in the small intestine and largely passes into the large intestine.
A small part of this mannitol might diffuse into the bloodstream (depending on how permeable your gut wall is) and the rest serves as a prebiotic and gets broken down into beneficial by-products by gut microbes.
When given via IV, mannitol serves to draw out water from cells that in turn reduces the thickness (viscosity) of the blood. Once this fluid-rich blood reaches the kidneys and goes through the process of filtration, nephrons (numerous small filtration units present in the kidney) filter out mannitol, toxins, and excess body water which gets excreted in the urine.
All the different sugar alcohols such as sorbitol, maltitol, etc., have fewer calories and sweetening intensities compared to table sugar. Different sugar alcohols act as prebiotics and feed different types of bacteria in the gut.
Sugar alcohols act as prebiotics
Sugar alcohols are prebiotics - the gut microbiome can break them down into beneficial short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids in the large intestine and used by the body. Butyrate feeds intestinal cells and supports a healthy gut barrier.
But depending on an individual’s sensitivity, for instance, individuals with irritable bowel syndrome (IBS) or known sensitivities to FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) may have a laxative effect or feel gastrointestinal discomfort such as cramping and bloating because these are fermentable.
Several studies have examined the effects of non-nutritive sweeteners (zero-calorie artificial sweeteners) such as saccharin, acesulfame K, aspartame, advantame, etc., on gut health. A paper published in Gut Microbes in 2023 suggested that increased consumption of artificial sweeteners may lead to an increase in oxidative stress and an increase in the transfer of antibiotic-resistant genes amongst the gut microbiome.
Besides a decrease in gut diversity, according to the web-based NutriNet Santé population-based cohort study set up to evaluate the relationship between nutrition and health from 2009 to 2022, artificial sweeteners, especially acesulfame K and aspartame, have been associated with an increased risk of cancer.
Potential health benefits of mannitol
Mannitol is a part of the World Health Organization’s (WHO) Model Lists of Essential Medicine since 1977. Food and Drug Administration (FDA) approved uses of mannitol include but are not limited to use in relieving brain swelling, inducing urination in case of kidney failure, increasing bioavailability of medicines, etc.
Besides clinical uses, several studies have explored the potential benefits of mannitol as an oral dietary supplement. These findings include:
Mannitol has antioxidant properties
Mitochondria are the energy factories of the cell and in the process of generating energy, they generate several reactive oxygen species (ROS) - superoxide anion, hydrogen peroxide, and hydroxyl radical. Production of ROS is a part of regular cellular processes and they are neutralized systemically. However, an increase in ROS beyond the neutralizing capacity of the body has been associated with several inflammatory disorders and the pace of the aging process.
Several studies supported the use of mannitol as a powerful ROS scavenger, capable of neutralizing ROS species such as hydroxyl radicals and hydrogen peroxide.
Mannitol might aid in weight management
The results of a study conducted in mannitol-supplemented mice over 28 days concluded that mannitol supplementation decreased fat digestibility and fat accumulation besides lowering blood cholesterol levels.
In another study, mannitol supplementation was associated with increasing brown adipose tissue (BAT) from white adipose tissue (WAT). White and brown adipose tissue have opposite functions, where WAT stores excess fat as triglycerides, BAT contains smaller lipid drops and more mitochondria. BAT increases energy consumption (metabolism) via heat generation because of shivering and thus is associated with weight loss.
Mannitol and Parkinson’s Disease
The probable use of mannitol as a supplement that might provide aid in movement disorders such as Parkinson's Disease first came to light in 2013. A study published in the Journal of Biological Chemistry concluded that mannitol may disrupt the formation of alpha-synuclein (α-syn) clumps.
α-syn clumping is an important identifying marker for Parkinson's disease (PD). The effects of mannitol supplementation in PD models of Drosophila (fruit flies) and mice suggested that mannitol might have a beneficial effect as a therapeutic agent in Parkinson's disease.
An effort to gather data regarding the effects of mannitol supplementation on Parkinson's symptoms led to the establishment of crowd-funded Clinicrowd, a data-collecting website for Parkinson’s patients across the world who were taking mannitol as a supplement.
The data collected via Clinicrowd suggested participating Parkinson’s patients observed an improvement in their sense of smell. Watch as Dany Vesely, an army veteran, and Sagit Weiss, a physician, and immunologist, share their experiences with mannitol and Parkinson’s in My Disease Our Revolution, and in this interview.
Effects of mannitol as a Prebiotic
Several metabolic and inflammatory disorders such as diabetes and inflammatory bowel disease (IBD) can be traced back to dysbiosis. Dysbiosis is an imbalance in the gut microbiome which typically shows up either as a lack of diversity in gut microbes or an overabundance of pathogenic bacteria.
A healthy and diverse gut microbiome requires a diet rich in complex carbohydrates (prebiotics) and probiotics (fermented foods and/or probiotic supplements) along with optimum sleep and exercise.
Prebiotics are described as non-digestible food ingredients that are resistant to digestion but can be fermented by intestinal microflora, stimulating the growth and activity of intestinal bacteria associated with health and well-being.
Complex carbohydrates such as fructooligosaccharides (FOS), galactooligosaccharides (GOS), pectin, inulin, resistant starch, sugar alcohols (mannitol, sorbitol), etc found in whole plant-based foods such as garlic, onion, artichoke, dandelion greens, lentils and legumes, and chicory root, etc. have been associated with health benefits such as improvement in the diversity and abundance of beneficial gut microbes.
The results of an animal study found that fermentation of mannitol in the gut led to the production of butyrate and propionate which supports intestinal cell health and confers anti-inflammatory effects in the body.
It’s well established that fermentation of sugar alcohols in the gut leads to the production of short-chain fatty acids such as butyrate and propionate that are essential for gut health and have been correlated with improvement in markers such as blood sugar, body weight, and triglycerides levels in metabolic disorders such as obesity and diabetes. This is why our Sugar Shift probiotic, which converts surplus glucose and fructose into mannitol and helps produce butyrate, is so effective.
A healthy gut microbiome supplies the body with several metabolites besides SCFAs (short-chain fatty acids) such as bacteriocins - that inhibit the growth of pathogenic bacteria - neurotransmitters and precursors to neurotransmitters such as dopamine, serotonin, and glutamate and enhance the release of satiety and insulin sensitivity influencing hormones such as Glucagon-like peptide 1 (GLP 1) and Peptide YY (PYY).
Besides keeping us supplied with essential metabolites, a healthy and diverse gut microbiome also keeps the integrity of the gut barrier wall. It inhibits the passage of endotoxins like lipopolysaccharides (LPS) from passing into the bloodstream and inducing an immune response.
A double-blind, placebo-controlled study testing the metabolic efficacy of Sugar Shift® found a significant decrease in circulating LPS and an improvement in insulin sensitivity at the end of 12 weeks. Sugar Shift® is a proprietary formula that contains a mix of bacterial strains that convert excess glucose and fructose into mannitol and might help increase probiotic populations in the gut.
A narrative review studying the relationship between prebiotics and type 2 diabetes published in 2020 concluded that there’s a strong clinical potential for prebiotics in blood sugar control in type 2 diabetes.
A study exploring the effects of mannitol and additional complex carbohydrates on 10 patients newly diagnosed with type 2 diabetes mellitus concluded prebiotics like mannitol can enhance the abundance of beneficial probiotics such as Lactobacillus and Bifidobacterium.
Mixing it up - Mannitol and probiotics
Diversity in the gut microbiome is an important cornerstone when evaluating the health-giving or disease-fostering effects of gut microbes. The gut microbiome is a complex ecosystem where each microbial species plays a part in making the entire system work.
Not all bacterial species ferment or break down carbohydrates, while primary fermenters break down complex carbohydrates, secondary fermenters feed on the by-products of primary fermentations to produce additional beneficial metabolites such as SCFAs. Cross-feeding and nutrient competition are essential to the maintenance of a healthy gut. Our deep understanding of these team dynamics is what makes us different.
With the help of our proprietary BioFlux® Model, we have developed Sugar Shift®, a first-of-its-kind probiotic calibrated for how different microbial communities function and work together to affect metabolism and health.
Listen to The Kick Sugar Coach podcast, Exploring Gut Health and the Sugar Connection hosted by Florence Christophers, as I go into more detail about how Sugar Shift® can help you kick sugar.
For instance, beneficial bacterial strains such as Leuconostoc mesenteroides (TBC LM-37™) and Lactobacillus reuteri (PCR07) can convert excess glucose and fructose into mannitol, which has been associated with enhancing probiotic communities in the gut besides being a powerful free radical scavenger which is excreted via urine.
Frequently Asked Questions
What is a mannitol supplement?
Mannitol is a sugar alcohol - a complex carbohydrate found in vegetables such as mushrooms and asparagus. It is used as a sugar alternative in diabetic foods and clinical practice, as an osmotic diuretic.
Is mannitol safe in supplements?
Mannitol is safe to consume up to 20 gm but it might lead to gastrointestinal discomforts such as bloating, gas, cramping, or diarrhea for individuals with IBS or known FODMAP sensitivity.
Is mannitol sold over the counter?
Mannitol is commonly used as a sugar alternative and is available over the counter.
Is mannitol good for you?
Several studies support the potential health benefits of mannitol as a prebiotic.With gratitude,
Martha Carlin, is a “Citizen Scientist”, systems thinker, wife of Parkinson’s warrior, John Carlin, and founder of The BioCollective , a microbiome company expanding the reach of science and BiotiQuest, the first of it’s kind probiotic line. Since John’s diagnosis in 2002, Martha began learning the science of agriculture, nutrition, environment, infectious disease, Parkinson’s pathology and much more. In 2014, when the first research was published showing a connection between the gut bacteria and the two phenotypes of Parkinson’s, Martha quit her former career as a business turnaround expert and founded The BioCollective to accelerate the discovery of the impact of gut health on all human disease. Martha was a speaker at the White House 2016 Microbiome Initiative launch, challenging the scientific community to “think in a broader context”. Her systems thinking background and experience has led to collaborations across the scientific spectrum from neuroscience to engineering to infectious disease. She is a respected out of the box problem solver in the microbiome field and brings a unique perspective to helping others understand the connections from the soil to the food to our guts and our brains.
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