The Difference Between Fructose Malabsorption and Hereditary Fructose Intolerance

Updated April 2017

The following piece of writing is intended to be informational only. If you have any concerns regarding FM or HFI, please see your healthcare practitioner. Unless you have HFI or FM/IBS, there is generally no need to follow the fructose free or fructose friendly diets. Before starting a low fructose diet for the other health issues mentioned below, I highly recommend seeing a doctor or dietitian to check if it is the right course of action for you.

glucose-fructose-sucrose-fodmap-hfi

Fructose Malabsorption (FM) and Hereditary Fructose Intolerance (HFI) are two different disorders with such similar names and the same sweet culprit – no wonder people get confused. So much so that FM was actually renamed from Dietary Fructose Intolerance, to prevent mix ups.

If you have been following any health websites over the last few years, you will have heard that excessive consumption of dietary fructose – a 6 carbon monosaccharide (sugar) common to fruits and vegetables, with the chemical formula C6H12O6, the same as glucose – has been labelled as the cause of many health issues, such as non-alcoholic fatty liver disease, the obesity epidemic, changes in your blood-lipid profile, increased risk of cardiovascular disease and atherosclerosis. 1,2,3 And this is just in people without any problems absorbing or metabolising fructose. I mention this because, even removing FM and HFI from your search, fructose is plastered everywhere, just adding to the confusion. So far we have the:

  • Fructose Free diet for HFI
  • Fructose Friendly diet (which falls under the FODMAPs umbrella) for FM
  • Low Fructose diet being publicised by books like I Quit Sugar or Sweet Poison

Please note I am not disagreeing with any of these, I am just highlighting how the tiny differences in nomenclature can lead to confusion for the uninitiated. Which diet should you follow, if any?

Once you have decided that you are having issues with fructose, it is time to start the search for answers. The rest of this post will discuss FM and HFI, about which I aim to outline the aetiology, signs/symptoms, diagnosis, treatment and prognosis, so you can see the similarities and differences between the two disorders.

Fructose Malabsorption

Aetiology

An inability to absorb fructose from the small intestine, due to malfunctioning GLUT-5 protein channels, leads to dietary fructose consumed in excess of glucose remaining in the intestine and reaching the colon. Your colon is full of multiple colonies of bacterium, which are necessary for our health,4 that then proceed to feed on the fructose; their method of choice is fermentation, which results in carbon dioxide and hydrogen and/or methane gas, as well as short chain fatty acid production and increased water content due to osmosis. The products of fermentation lead to IBS (irritable bowel syndrome) like symptoms, which are generally what drives a person to seek a diagnosis.

Those with FM are also generally more sensitive to fructans (or “fructooligosaccharides”/FOS), which are indigestible fibres for all mammals, even non-FMers. Your gut microbiota will also ferment the FOS, leading to the same resulting by-products as fructose fermentation. For a more complete description, read my earlier post, entitled, “What is Fructose Malabsorption?

Signs/Symptoms

Ingesting excess free fructose can result in a variety of symptoms, not all of which are related to irritable bowel syndrome. An example of symptoms could include (but are definitely not limited to):

  • Abdominal pain.
  • Altered bowel movements – constipation or diarrhoea.
  • Bags under your eyes.
  • Bloating.
  • Confusion, also known as “brain fog.”
  • Dizziness.
  • Fatigue.
  • Flatulence/gas.
  • Gastro-oesophageal reflux disease (GORD) style symptoms, such as heartburn.
  • Mental depression. 12
  • Nausea.
  • Night sweats.
  • Poor absorption of vitamins and minerals, which can lead to secondary health issues.
  • Skin issues – puffy skin, pimples etc.
  • Stomach ache.
  • Vomiting.

The non-digestive symptoms are harder to pinpoint as being related to fructose but, with a detailed food and symptom diary, it can be done. For instance, it took me a while but I realised that a trigger for my sinus issues is eating wheat, which also causes me to get little pimples on my chin and hairline and night sweats. As my digestive symptoms after eating wheat weren’t too severe (mild bloating and discomfort), I was ignoring them and still occasionally eating wheat-based treats, which eventually led me to discover links between wheat and the other, apparently more random, symptoms.

Diagnosis

The current diagnostic tool for FM is the hydrogen/methane breath test. Breath test protocol is as follows:

  • No antibiotics, colonoscopies or barium enemas or probiotic supplements in the month leading up to the test. 5
  • Restricted carbohydrates and no laxatives or high fibre foods in the 24 hours before the test. 5,6
    • Your testing clinic will give you more specific instructions for the lead up to the test.
  • Fast completely for 12 hours before the test. 5
  • You will then take a baseline breath reading before drinking a fructose solution, which is typically 35 g fructose dissolved in 300 ml of water. 5 After this, you will record breaths every half hour for approximately three hours. 5,6

Results are generally sent to your referring health practitioner for interpretation, however FM is generally diagnosed with an increase of more than 20 ppm of hydrogen (or more than 10 ppm of methane) levels over your baseline reading twice in succession. 6

An elimination diet can also be undertaken, to discover which foods stir up symptoms; then you can work out what the common factor between all your trigger foods may be. The basic method of an elimination diet would be to cut out all foods that contain known gut irritants, such as FODMAPs, gluten and casein (etc) for a period of six to eight weeks (generally speaking) and then slowly introduce new foods (one per week) to see if you react. A nutritionist, dietitian, doctor or a naturopath would be best to help you structure an elimination diet specific for your situation – a food/symptom diary would also be very helpful.

Management

FM symptoms are managed primarily through a change in diet:

  • Limit free fructose intake to less than an excess of 100.5 g fructose for every 100 g of glucose.
  • Limit your total fructose load per meal, regardless of a higher glucose intake.
  • Limit your intake of FOS, eating less than 0.5 g per sitting.
  • Other FODMAPs might be causing you issues, an elimination diet or further breath testing may help you to discover which.

In addition to following a “fructose friendly” diet, the following methods might be employed for symptom management:

  • Glucose/dextrose might be useful as a supplement to even out the f:g ratio, though this only works for fructose and not FOS, and even then works best when the glucose is actually IN the food. Please note that this is generally used as an emergency action only and does not work for everyone. I would personally not sprinkle glucose on an apple and see if I could eat it.
  • Probiotics (tablets or lacto-fermented foods) can help to re-balance your gut microbiota, which should hypothetically improve your gut health and reduce your sensitivity to foods high in excess fructose/FOS. 7 It is not as easy as just popping a daily probiotic for some, though, as it depends on which bacterial strains you may be deficient in and whether you have a confounding disorder, such as SIBO, which would be exacerbated by taking probiotics.
  • Multivitamins can help to maintain your nutrients and thus your body’s ability to properly digest foods – carbohydrates, fats and proteins alike. This would mean that there are less substances in your colon that shouldn’t be there, so the chance of an irritation is reduced. Vitamins to concentrate on would include the B group, C and D, as well as zinc, calcium and magnesium. 8 Once again, this might not work for everyone and should be done with the help of a health practitioner.
  • Ginger can calm upset stomachs and is low FODMAP. 9
  • L-Glutamine is a supplement that supports intestinal health and may assist some people with absorption of nutrients. 7
  • A product like Buscopan or Beano may help to manage flare ups (I am not endorsing any of these or saying they are safe, just listing them as examples).
  • Xylose isomerase is an enzyme that catalyses fructose metabolism and has demonstrated an ability to assist with symptom control. 10
  • Water to maintain hydration.
  • Other methods, such as meditation and yoga for stress reduction and gentle physical activity to help reduce cramps.

Prognosis

As of the time of writing, there is no currently known or accepted method by which FM can be cured, symptom management is achieved through diet control. 10 There are instances where sensitivity can come and go over time – I experienced this once myself – however the FM remains, the IBS lying dormant.

There are subjective reports of people having found that, once they have been following a strict low FODMAP (and often gluten free) diet, they have been able to slowly re-introduce foods that they were previously unable to eat, though this takes time, often years – for example, I was able to introduce garlic and onion after 3 years. The hypothesis is that because the gut is not as distressed (inflammation etc), it is able to tolerate moderate loads of FODMAPs.

I have even heard of a very new procedure in Germany that claims to heal FM by correcting the autonomic nervous system’s control of digestion. The hypothesis is that the ANS insufficiently activates the GLUT-5 transport proteins that are responsible for fructose absorption, thus leading to free excess fructose remaining in the intestine and passing into the colon. By addressing this issue, the ANS is able to correctly pair instructions to the GLUT-5 transport proteins with fructose ingestion.11 However exciting this may sound, I was only able to find the one link and no peer reviewed, blinded trials have been published to date – so I would not say that this is a definite/reliable cure. Hopefully this will change in the future!

Hereditary Fructose Intolerance

Aetiology

HFI is an autosomal recessive disorder of the ALDOB gene, 17 characterised by a deficiency of the liver (and kidney/intestinal) enzyme, aldolase B, which is responsible for metabolising fructose and gluconeogenesis (generating glucose from non-carbohydrate substrates). 13

Other names for HFI include: ALDOB deficiency, aldolase B deficiency, fructose-1-phosphate aldolase deficiency, fructose intolerance or fructosaemia, to name a few. 17

In healthy subjects, the aldolase B catalyses the reversible cleavage of fructose-1-phosphate (F1P) into glyceraldehyde and dihydroxyacetone phosphate (DHAP); this is demonstrated in the image below. In those with HFI, this does not occur and the F1P accumulates in the liver to potentially toxic levels, leading to hyperphosphataemia, as well associated hypoglycaemia, due to the competitive inhibition of the phosphorylase enzyme by F1P, thus impairing glucose homeostasis. 13,14

liver-metabolism-fructose-aldolase-b-enzyme-hfi

Signs/Symptoms

Signs and symptoms of HFI are caused by the interruption to the metabolic pathway of F1P and include:

  • An aversion to sweet tasting foods,
  • Abdominal discomfort,
  • Bloating,
  • Coma,
  • Death,
  • Failure to thrive in infants,
  • Growth retardation,
  • Hypoglycaemia (low blood glucose),
  • Jaundice,
  • Kidney faliure,
  • Liver failure – hepatomegaly and/or cyrrhosis,
  • Nausea,
  • Renal tubular dysfunction,
  • Seizures,
  • Vomiting. 13,14,15,17

Diagnosis

There are (currently) two tests that can be used to determine if an individual has HFI, which are:

  • An enzymatic assay – an invasive liver biopsy is performed, after which the sample’s enzyme activity is assessed.
  • A fructose tolerance test – a fructose solution is injected into the circulatory system and glucose, fructose and phosphate levels are closely monitored. 16

A third test exists, which involves a blood draw and subsequent genetic screen for mutations of the aldolase B gene, three of which apparently account for more than 75% of HFI mutations in Europeans and Americans. However, this test is not considered diagnostic, as less than 5% of possible aldolase B mutations are known to researchers. This means that the genetic screen is used more as a guideline in aiding diagnosis, as a negative result does not automatically rule out HFI if the individual carries mutations that have not yet been discovered. 18

The hydrogen breath test used to diagnose FM will not diagnose HFI; however, it is possible that individuals with HFI may test positive to FM. 16

Treatment/Management

HFI is treated through management of your diet, including the elimination of sugars that are metabolised through the F1P pathway, including fructose, sucrose (a fructose-glucose disaccharide) and sorbitol, to less than 40 mg/kg of body weight/day. This fructose free diet should completely resolve most symptoms and result in a normal life span. 14 Unlike the fructose or FODMAP friendly diets, the use of glucose to “balance out” the fructose will not make a difference to those with HFI, as the problem is with how the fructose is processed once it’s inside the body, not with absorption.

Prognosis

Infants are most at risk of toxicity and liver failure due to undiagnosed HFI, which, for them, is potentially lethal. If an older child/adult complies with a fructose free diet, HFI symptoms should resolve and a normal life span is expected. If the HFI goes undiagnosed, or the patient continues to consume fructose in excess of 40 mg/kg body weight per day, then symptoms and comorbidities listed above will continue. 13

References

  1. Bray, GA (2007). How Bad is Fructose? http://ajcn.nutrition.org/content/86/4/895.full.pdf+html
  2. Bray, GA, Nielson SJ, Popkin, BM (2004). Consumption of HFCS in Beverages May Play a Role in the Epidemic of Obesity. http://ajcn.nutrition.org/content/79/4/537.full.pdf+html
  3. Bray, GA (2005). Adverse Effects of Dietary Fructosehttp://www.ncbi.nlm.nih.gov/pubmed/16366738
  4. Cummings, JH, Macfarlane, GT (1997). Role of intestinal bacteria in nutrient metabolismhttp://www.clinicalnutritionjournal.com/article/S0261-5614(97)80252-X/abstract
  5. GastrolabTV. Gastrolab – Hydrogen and Methane Breath Testing for Sugar Malabsorption Explainedhttp://www.gastrolab.com.au/patient-information/video-hydrogen-methane-breath-testing-explained.html
  6. Wilder-Smith, CH, Materna, A, Wermelinger, C, Schuler, J (2013). Fructose and lactose intolerance and malabsorption testing: the relationship with symptoms in functional gastrointestinal disordershttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672687/pdf/apt0037-1074.pdf
  7. WebMD. 8 Digestive Health Supplementshttp://www.webmd.com/vitamins-and-supplements/lifestyle-guide-11/slideshow-digestive-health
  8. http://www.livestrong.com/article/371412-vitamins-that-aid-digestion/
  9. Not From A Packet Mix (2013). Chocolate and ginger root… No, don’t pull a facehttp://wp.me/p3g4oZ-BS
  10. Komericki P, Akkilic-Materna M, Strimitzer T, Weyermair K, Hammer HF, Aberer W. Oral xylose isomerase decreases breath hydrogen excretion and improves gastrointestinal symptoms in fructose malabsorption – a double-blind, placebo-controlled study. http://www.ncbi.nlm.nih.gov/pubmed/23002720
  11. Systematic elimination of fructose malabsorption within three days.https://docs.google.com/file/d/0BxIq6H_bnmx7eHZKaW0xS2NtQ3M/edit
  12. Ledochowski M, Widner B, Murr C, Sperner-Unterweger B, Fulchs D. Fructose Malabsorption is Associated with Decreased Plasma Tryptophanhttp://www.fructose.at/pdf/works/11336160.pdf
  13. Tolan Laboratory at Boston University. Aldolase. http://www.bu.edu/aldolase/lab/research.html#AldB
  14. HFI Laboratory at Boston University. Specifics of HFI and its Diagnosishttp://www.bu.edu/aldolase/HFI/hfiinfo/detail.html
  15. HFI Laboratory at Boston University. What is HFI? http://www.bu.edu/aldolase/HFI/hfiinfo/index.html
  16. HFI Laboratory at Boston University. How is HFI diagnosed? http://www.bu.edu/aldolase/HFI/diagnosis/index.html
  17. Genetics Home Reference. Hereditary Fructose Intolerance. http://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance
  18. HFI Laboratory at Boston University. Our HFI Genetic Test. http://www.bu.edu/aldolase/HFI/hfitest/hfitest.html