Key takeaways:
~ Fructose intolerance can be hereditary (genetic) or due to intestinal absorption problems.
~ Genetic mutations in the ALDOB gene can cause hereditary fructose intolerance.
~ Carriers of a single ALDOB mutation can still process some fructose, but they may be prone to insulin resistance with higher fructose consumption.
Members see their genotype report below, plus solutions in the Lifehacks section. Consider joining today.
What is fructose intolerance?
Fructose intolerance causes digestive problems, such as nausea, diarrhea, bloating, gas, and abdominal pain, after eating foods that contain fructose.
Fructose is a sugar found in fruits and vegetables. People with fructose intolerance may need to avoid many fruits, juices, honey, table sugar, peas, zucchini, asparagus, maple syrup, sorghum, molasses, agave, palm sugar, coconut sugar, and corn syrup. According to the Mayo Clinic, some fruits with low fructose content, such as blueberries, bananas, avocados, strawberries, and carrots, may be okay in limited amounts with meals. Sorbitol should also be avoided.[ref]
How is fructose absorbed in the small intestine?
While fructose and glucose are similar sugars in many ways, their absorption is a little bit different.
- Glucose is completely absorbed in the small intestine and is facilitated by GLUT2 and GLUT5 transporters. Glucose can be absorbed without the transporters.
- Fructose is absorbed through carrier-mediated facilitative diffusion and with GLUT5 transporters. Without adequate transporters, fructose may not be completely absorbed and thus ends up in the colon.
Dietary vs. Hereditary fructose intolerance:
Fructose intolerance can be classified as either hereditary or dietary fructose intolerance.
Hereditary fructose intolerance is caused by rare mutations in the ALDOB gene and is present from birth.
Dietary fructose intolerance shares many of the symptoms of hereditary fructose intolerance, but the disorder is caused by fructose transporters in the intestine.
Let’s start with hereditary fructose intolerance…
What happens in hereditary fructose intolerance?
In hereditary fructose intolerance, two copies of mutations in the aldolase B (ALDOB) gene cause the enzyme not to function. Aldolase B breaks down fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate in the liver. [ref]
The inability to break down fructose 1-phosphate causes phosphate trapping and ATP depletion in the liver. Additionally, it inhibits glycolysis and gluconeogenesis, leading to hypoglycemia or even lactic acidosis. The buildup of phosphate causes uric acid to rise.
In hereditary fructose intolerance, liver and kidney dysfunction will eventually occur.[ref]
Hereditary fructose intolerance is rare and found in 1 in 10,000 people.[ref] It is usually diagnosed in infants when they are introduced to fructose-containing foods.
However, it is estimated that around 1 in 80 people carry a single copy of an ALDOB mutation, which may cause issues with consuming larger amounts of fructose in one sitting.[ref]
Can hereditary fructose intolerance be diagnosed in adulthood?
A case study showed that a 41-year-old woman who reported sweating, nausea, and vomiting after consuming sweets actually carried two mutations in the ALDOB gene. She had avoided eating sweets since infancy. This instinctive avoidance of foods containing fructose meant that she had no negative effects, with normal laboratory findings. [ref]
What happens if you have one copy of a hereditary fructose intolerance mutation?
Carrying one copy of an ALDOB mutation decreases the enzyme efficiency to about 50%. This is usually enough of the functional enzyme to digest moderate amounts of fructose.
A study of people carrying one ALDOB mutation showed that eating a meal high in fructose causes increased fasting uric acid, reduced fasting insulin sensitivity, and increased insulin resistance.[ref]
Thus, while mutation carriers likely will not have acute symptoms of hereditary fructose intolerance, limiting the amount of fructose consumed may help with metabolic health.
Dietary fructose intolerance or fructose malabsorption:
Dietary fructose intolerance causes bloating, abdominal pain, and diarrhea due to fructose not being absorbed in the small intestine and traveling through to the large intestine. It is often misdiagnosed as IBS. [ref]
Fructose is transported across the epithelial cells in the intestines by the GLUT-5 or GLUT-2 transporters, which also transport glucose and galactose.
Researchers theorize that consuming fructose along with glucose or galactose can upregulate the GLUT receptors and decrease problems with fructose malabsorption.
Excess fructose consumption at one time can overwhelm the transport system in the small intestines.[ref]
When fructose isn’t completely absorbed in the small intestine, it ends up in the large intestine where it gets fermented by bacteria, causing bloating, gas, and loose stools.[ref]
Tests for fructose malabsorption and intolerance use a breath test to determine the amount of hydrogen being produced by the gut bacteria. [ref]
There have been no human gene variants identified that relate to fructose malabsorption.
Studies in mice show that a protein, ChREBP, that regulates the number of GLUT-5 transporters may play a role in causing dietary fructose intolerance.[ref] This indicates that dietary fructose intolerance is likely due to decreased GLUT-5 transporters.
Fructose Intolerance Genotype Report
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the members-only information in the Lifehacks sections.
ALDOB gene: Rare mutations in the ALDOB gene cause hereditary fructose intolerance in people with two copies. For someone with one copy of a mutation, insulin resistance is possible with higher fructose intake.
Check your genetic data for rs78340951 (23andMe v4, v5 i5012664; AncestryDNA)
- G/G: typical
- C/G: Carrier of a fructose intolerance mutation
Members: Your genotype for rs78340951 is — or for i5012664 is —.
Check your genetic data for rs76917243 (23andMe v4, v5 i5008215; AncestryDNA)
- G/G: typical
- C/G: Carrier of a fructose intolerance mutation[ref]
Members: Your genotype for rs76917243 is — or for i5008215 is —.
Check your genetic data for rs1800546 (23andMe v4, v5; AncestryDNA)
Members: Your genotype for rs1800546 is —.
Check your genetic data for rs387906225 (23andMe v4, v5 i5012665; AncestryDNA)
- I/I: typical
- D/I: Carrier of a fructose intolerance mutation[ref]
Members: Your genotype for rs387906225 is — or for i5012665 is —.
Check your genetic data for rs118204428 (AncestryDNA)
- G/G: typical
- A/G: Carrier of a fructose intolerance mutation[ref]
Members: Your genotype for rs118204428 is —.
Lifehacks:
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
Member Content:
An active subscription is required to access this content.
Join Here for full access to this article, genotype reports, and much more!
Already a member? Log in below.
Related articles and topics:
Histamine intolerance:
Many healthy foods also contain histamine, which may cause problems for people with certain genetic variants.
Lactose intolerance: check your genes
You can easily see whether you genetically produce lactase as an adult.
About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.