Rare Genetic Disorders: Hereditary Fructose Intolerance (HFI)
What Is Hereditary Fructose Intolerance (HFI)?
Hereditary fructose intolerance (HFI) is a rare genetic disease in which fructose cannot be properly metabolised in the body. Affected person suffers from a bad abdominal reaction (bloating, diarrhea, generalized malaise) after eating fructose-containing foods. HFI is an autosomal recessive disorder of fructose metabolism, due to a deficiency of fructose-1-phosphate aldolase – an enzyme that converts fructose into glucose in the liver. Incidence of HFI is estimated at 1 / 22-58,000 people (1).
HFI should be differed from fructose malabsorption.
Patophysiology of HFI
Absorbed fructose is normally converted into fructose-1-phosphate, and further into glucose in the liver. In HFI, fructose-1-phosphate, due to lack of enzyme fructose-1-phosphate aldolase, cannot be converted into glucose, so it accumulates in liver, intestine, and kidneys, and inhibits glucose synthesis, thus causing hypoglycemia.
Prolonged fructose ingestion in infants may cause hepatic or renal failure and death. Fructose-1,6-diphosphate deficiency is another form of fructose intolerance, which usually presents as neonatal hypoglycemia.
Symptoms of HFI
Infants have no symptoms until they try fructose containing food. Symptoms may vary from less to more severe in different individuals.
Most commonly observed symptoms in HFI:
- Bloating, flatulence
- Abdominal pain, vomiting
- Symptoms of hypoglycemia: sugar craving, tremor, fainting, and in severe cases convulsions, coma
- Fatigue, depression
Long term effects of HFI (due to iron and vitamin deficiencies):
- Poor skin, nails and hair
- Generally feeling ill
Diagnosis of HFI
From the personal history it can be seen, that HFI individual refuses sweet food. Family history may reveal relatives with HFI. Diagnostic possibilities are:
- Reducing sugars in the stool can be the first test. If reducing sugars are increased, further test to identify fructose can be done.
- Blood tests may reveal elevated bilirubin and hepatic enzymes.
- In a fructose tolerance test, fructose is injected intravenously and glucose, fructose, and phosphate levels in the blood are monitored. In HFI, glucose will not rise after fructose injection.
- Biopsy of liver and determining of activity of fructose-1-phosphate aldolase.
- DNA test has many false negative results. Positive test, along with symptoms, disappearing after onset of a fructose-free diet, strongly speaks for HFI.
NOTE. Hydrogen breath test with fructose is positive, but it cannot distinguish between fructose malabsorption and HFI.
Treatment of HFI
Treatment for HFI is currently not available.
Diet in Hereditary Fructose Intolerance
Strict long-life fructose-free diet is essential. Fructose, sucrose (glucose + fructose), and sorbitol (may be converted into fructose in the body) should be completely eliminated from the diet. Some persons with HFI can not tolerate fructans (chains of fructose with glucose on the end), and raffinose (galactose + glucose + fructose).
Dramatic improvement after the onset of a diet can be usually observed in few days. It can take several weeks to achieve full digestion recovery though.
Foods to EXCLUDE in HFI (NON-complete list!):
- Fruits (contain fructose and sorbitol) in any form, including fruit juices, compotes, jams, ice cream, and so on; some individuals with HFI can safely eat lemons
- Vegetables/cereals with fructose: beets, carrots, chick peas, egg plant, garlic, green peas, iceberg lettuce, leeks, onions (but shallots can be tried), parsnip, swede, new white potatoes, sweet potatoes (including yellow potatoes, like Yukon Gold), sweet root, tomatoes, turnip, yam, zucchini
- These cereals: brown rice, cous cous (plain), germs (wheat or any other germs), whole-grain breads, bran
- Nuts: “officially” they are not allowed, but many can tolerate small amount of some types
- Honey (contains fructose)
- Alcohol: many wines, beers, and distilled beverages contain sucrose or fructose (some HFI individuals can try small amounts of dry wine)
- Sugars (sucrose, fructose or sorbitol) in sweets, sauces, salad dressings, soft drinks and alcohol, sweetened cereals/breads/dairy/processed meats, most canned foods:
- Brown sugar
- Carob powder
- Fructose (levulose)
- Hydrogenated starch hydrolysates (HSH)
- Invert sugar (golden syrup, treacle, trimoline)
- Licorice (sweet root)
- Litesse (polydextrose)
- Raw sugar (date sugar, Turbinado, Demerara, Muscovado – Barbados sugar, jaggery, palm sugar = gur, java or coconut sugar, panela, rapadura, sucanat)
- Saccharose (sucrose = table sugar, vanilla sugar, beet sugar, cane sugar, rock sugar)
- Sucralose (splenda)
- Syrups (agave syrup: in Tex-Mex foods, tequila, margaritas, soft drinks; brown rice syrup, barley malt syrup, corn syrup solids, fruit juice concentrate, fruit syrup, Squash, Cordial; High Fructose Corn Syrup (HFCS or isoglucose), karo syrup, maple sugar and syrup, shorghum syrup)
- Other sweeteners: stevia
- Sorbitol: “sugar free” chewing gum, “low calorie” foods and drinks, many sweetened foods, pills and syrups check labels); maltitol or lycasin, and isomalt may yield sorbitol;
- foods with inulin or fructo-oligo-saccharides (FOS) on labels, or E-numbers: E420 (sorbitol), E473 and E474 (sugar esters), E491-E495 (sorbitan esters, sorbitol may be released), E953 (isomalt).
Registered and experienced nutritionist has to be consulted to get exact diet recommendations.
Foods to TRY (SAFE for most but not all HFI persons):
- Legumes: beans (green, black or yellow wax beans may be OK), soy;
- High-fiber vegetables: broccoli, Brussels sprouts, green cabbage, lettuce, rhubarb
- Cereals: whole grains
- Corn products: cornchips, corn-flakes (plain), cornmeal (degermed), Dorritos, grits, Homeny, polenta, popcorn, puffed corn cereals, pure corn syrup (not HFCS or corn syrup solids), taco shells and tortillas;
- Anything sweet; some HFI persons can’t eat anything what tastes sweet regardless of sugar or sweetener used (acesulfam potassium: Nutrinova, Sweet One, Sunnett, Ace-K, Acesulfame K), aspartame, cyclamate, neotame, thaumatin.
- Cucumbers, potatoes (when potatoes are overcooked, or stored for a long time, some fructose may be released from the starch)
- Other FODMAPs: polyols (sugar alcohols): erythritol, dulcitol, lactalol, lacticol, mannitol, xylitol (birch sugar) are used as sweeteners in many commercial foods, like yogurts, chocolates, and other packaged foods; they are fermented by intestinal bacteria, what may result in gas and diarrhea; most HFI persons tolerate FODMAPS though;
- Toothpaste (to brush teeth only of course…): some brands of toothpaste contain sorbitol or fructose!
NOTE. Several people with HFI may have other food intolerances (lactose intolerance or celiac disease) or food allergies.
SAFE Foods in HFI:
- Meats, fish, shellfish and other seafood, but only if non-processed and not commercially breaded; packaged bacon often contains sugar; tinned fish without the sauce and smoked fish without cure is OK
- Fats: butter, oil, margarine without sweeteners
- Dairy products, non-sweetened
- Breads and cereals (but not sweetened or whole-grain), oatmeal, sunflower seeds;
- Vegetables: celery (raw), lettuce (red, oak leafed), mushrooms, spinach (without stems), tapioca, white rice;
- Sugars: dextrose, galactose, glucodin, glucose, glucose syrup, mannose, trehalose;
- Other carbohydrates: alginate, caragens, cellulose, dextrin, gellan gum, glucose polymers, glycogen, guar gum, gum arabic, gum tragacanth, isomaltose, locust bean gum, maltodextrin (modified starch), moducal, pectin, polycose, polydextrin, starch;
- Spices: bay, coriander, cumin, curry, cinnamon, oregano, salt, vinegar (distilled);
- Drinks: tap water, bottled but non-flavored water, mineral water, tea, soft drinks with allowed sugars (without fructose, sucrose, or sorbitol)
Detailed list of foods with/out FRUCTOSE
List of non/allowed SUGARS in HFI
- HFI (bu.edu)
- HFI incidence (bu.edu)
- Sugars and sweeteners , appropriate in HFI (bu.edu)
- Sugars and sweeteners description (thenibble.com)
- List of 2000+ fructose containing & fructose free foods (fineli.fi)