What is Hereditary Fructose Intolerance (HFI)?

Hereditary Fructose Intolerance (HFI) is a rare genetic disease in which fructose can’t be properly metabolised in the body. Affected person gets bad abdominal reaction (bloating, diarrhea) 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, which converts fructose into glucose in the liver. Incidence of HFI is estimated at 1 / 22-58,000 (1).

HFI should be differed from fructose malabsorption (dietary fructose intolerance - DFI).

Patophysiology of HFI

Fructose in the liver is normally converted into fructose-1-phosphate, and further into glucose. In HFI, fructose-1-phosphate, due to lack of fructose-1-phosphate aldolase, can’t be converted into glucose, so it accumulates in liver, intestine, and kidneys. The accumulated fructose-1-phosphate inhibits glycogen breakdown and glucose synthesis, thus causing hypoglycemia after fructose ingestion. Prolonged fructose ingestion in infants may cause hepatic or renal failure and death.

What are FODMAPs?

FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) are short-chain carbohydrates which have high osmotic activity (they drag water into intestine) and are regularly fermented by small and large intestinal bacteria.

FODMAPs include:

• oligosaccharides: fructans (inulin, fructo-oligo-saccharides (FOS) or oligofructose), galactans, and raffinose;
• disaccharides: lactose;
• monosaccharides: fructose;
• polyols: sorbitol, mannitol, xylitol, isomalt, erithrytol, arabitol, erythritol, glycol, glycerol, lactitol, ribitoll.  

Who Can Benefit from Low Sugar Diet?

People diagnosed with IBS, lactose intolerance, fructose malabsorption (Dietary Fructose Intolerance - DFI), Crohn’s disease, chronic diarrhea, toddler’s diarrhea, and those with ‘indigestion’, ‘dyspepsia’, unexplained bloating, or irregular bowels may all benefit from low sugar (FODMAPs) diet. FODMAP diet may be a way to lose weight in obese but otherwise healthy people.

Can FODMAP Diet be Dangerous?

FODMAP diet should not be introduced by any person with diabetes, hypoglicemia or other metabolic disorders, or in malnutrition without prior consultation with a doctor. It may be necessary to interrupt FODMAP diet in any severe acute disease, after injury or surgery, and in other urgent situations. 

What Symptoms Can FODMAPs Cause

FODMAPs malabsorption may result in bloating, gas, abdominal pain, diarrhea, weight loss, symptoms of vitamin and mineral  deficiency, headache, lethargy, and depression.

Low Fructose Diet (in DFI)

Persons with Fructose malabsorption (Dietary Fructose Intolerance - DFI) should limit foods high in fructose and sorbitol, and possibly foods high in fructans and other FODMAPs (Table 1).  The most problematic foods are those with high fructose : glucose ratio, or high sorbitol (11). 

Glucose enhances absorption of fructose, so moderate amount of foods with equal or low fructose : glucose ratio (e.g table sugar) should be OK…if they don’t contain sorbitol. Especially pre-prepared frozen foods and bakery, canned foods, low-calorie foods, and many artificially sweetened products have to be avoided. Labels should be checked for fructose and sorbitol.

Tolerance threshold for fructose may be as low as 1g of fructose per serving (25g / serving, or more, is considered as normal). Sorbitol: 10g of sorbitol may cause a diarrhea in a sensitive person. When fructose and sorbitol (and other FODMAPs) are combined in one food, relatively lower amount of each is needed to cause symptoms.  Fructose, sorbitol and FODMAPs may be naturally present in the food (fruits, vegetables, wheat) or they may be added during the food processing. On labels, fructose is hidden within ’sugars’, and sorbitol within ’sweeteners’, so their exact amount usually can’t be checked. Therefore, a person with fructose malabsorption should be aware of food ingredients (Table 1).

Below ‘foods to try’ and ‘to avoid’ were most often recommended / disadviced by doctors and fructose malabsorbers. Since each individual with DFI has its own fructose tolerance threshold, everyone has to build his/her personal list. Small amounts of problematic foods can be often safely ingested. Symptoms should lessen considerably in a couple of days after onset of low-fructose diet, and tolerance threshold for fructose may raise after some time. In small children fructose absorption increases with age (11). If symptoms don’t improve after 6-8 weeks of low-fructose diet, other diagnoses, like lactose intolerance and celiac disease, should be considered. Other causes of diarrhea.

Sugars to try: acesulfam pottasium (Nutrinova, Sweet One, Sunnett, Ace-K, Acesulfame K), barley malt syrup, brown rice syrup, corn syrup (if no fructose is added), dextrin, glucose (dextrose, glucodin), glycogen, grape syrup, maltodextrin (modyfied starch), maple syrup, moducal, sorghum syrup, sucrose (table or cane sugar), trehalose.

Sugars to avoid: agave syrup (in Tex-Mex foods, tequila, margaritas, soft drinks), brown sugar, caramel, chinese rock sugar (honey + added sugars), fructose, fruit juice concentrate, golden syrup (cane syrup), High Fructose Corn Syrup (HFCS - isoglucose), honey, invert sugar (treacle), licorice, molasses, raffinose (in legumes), raw sugar (Turbinado, Demerara, jaggery, palm sugar -gur); sugar substitutes: sorbitol, maltitol, mannitol, xylitol, hydrogenated starch hydrolysates (HSH), isomalt, erythritol, dulcitol, lactalol, lacticol, litesse, lycasin, saccharin (Sweet ‘n Low), stevia, sucanat, sucralose (splenda), trimoline (from beets). 

Fructose Malabsorption

In this article, fructose malabsorption, also known as Dietary Fructose Intolerance (DFI), which is a common cause of diarrhea, is described. Another, rare, Hereditary Fructose Intolerance (HFI), which causes impairment of liver, kidneys and small intestine is much more severe. DFI and HFI are NOT allergies.

In fructose malabsorption fructose can’t be efficiantly absorbed from unknown reason. Transport protein GLUT5, responsible for fructose absorption in the small intestine, may not be present or becomes inactive. People with fructose intolerance have fructose absorption limit lower than 25 grams per serving, but this may differ a lot from person to person. Fructose, unabsorbed in the small intestine, reaches the colon, where bacteria ferment it and yield short chain fatty acids, carbon dioxide (CO2), hydrogen and methane, which cause symptoms. It is estimated that about 1/3 of people are fructose intolerant, and about half of them have symptoms. People with fructose intolerance may be also sensitive to other non-digestable carbohydrates, such as sorbitol and xylitol, raffinose (beans) and inulin (polyfructose), (5).

Who Can Get Fructose Intolerant?

Anyone at any time can develop fructose intolerance. Abnormality or lack of GLUT-5, a fructose transporting protein, may be inherited (5). Other causes, suggested so far:

• family predisposition; 
• overuse of High Fructose Corn Syrup (HFCS), or fruit juices in children (toddler’s diarrhea); 
• small intestinal bacterial overgrowth (SIBO);
• celiac disease; 
• chemotherapy or radiation;
• dumping syndrome (rapid stomach emptying).

Candida Albicans

Candida albicans is a yeast (unicellular fungus), normally present on the human skin and mucosa of the gut, respiratory system and genitals; its amount is controlled by immune system and normal bacterial flora. Under certain circumstances, candida may overgrow, mainly in the vagina, mouth, esophagus, sinuses and rarely colon.

WARNING: Candida is rare in otherwise healthy people. Do not jump easily into a self-diagnosis of intestinal candida, just on the basis of some symptoms mentioned in this article. The only firm proof of intestinal candida is colonoscopy with a biopsy of colonic wall. Next: intestinal candida is NOT already a systemic candida.

What Causes Intestinal Candida Overgrowth?

Triggers of candida overgrowth:

1. During a long term antibiotic treatment many normal bacteria, attached to colonic wall are killed, thus releasing the space for yeasts (1).
2. Lowered immunity due to steroids, birth control pills, antacids, anti-ulcer drugs, chemotherapy, radiation therapy, immuno-suppressant drugs, AIDS, malignancy, diabetes, hypothyroidism, hypoparathyroidism, Addison’s disease, malnutrition, alcoholism, street drugs, or chronic stress, enables uncontrolled candida growth.
3. Sugars and other carbohydrates are food for yeasts and may quickly and markedly boost their growth.
4. Gastric hypo-acidity due to gastric disease, antacids, or anti-ulcer drugs, may allow candida to spread from the mouth into intestine (1).
5. Mouldy environment, like basement appartments in dump builduings, or wet cool climate may enhance yeast infections.

Candida Symptoms

Main symptoms of intestinal candida overgrowth are diarrhea (or constipation), pale or mucous stools, bloating, itchy anus, diaper rash in kids, oral thrush (greasy white patches on the tongue or mouth mucosa, Image 1), and craving for sugar. If candida enters the blood, e.g. in persons with lowered immunity, it causes systemic infection, present with vaginal discharge, burning at urinating, prominent fatigue, irritability, and it may be deadly. Symptoms improve after sugar-free diet and may dramatically worsen after the sugar-rich meal, what can be an useful diagnostic sign.

What Is a Diarrhea?

Diarrhea (from Greek ‘dia’ - through, ‘rhein’ - flowing) means having more than three bowel movements, or passing more than 300g of watery stool daily (1).

What Is Not a Diarrhea?

Ten diapers a day are usual in a 14 days old infant. Three soft bowel movements a day may be considered normal for adult on a fibre-rich diet. Stool soiling in children who are already toilet trained may be due to defective anus. Stool incontinence or mucus seeping in adults may be due to rectal inflammation, rectal prolapse, hemorrhoids, uncoordinated pelvic floor muscles, or anal muscle or nerve damage (2). In all mentioned cases, bowel movements tend to be of normal volume and consistency.

Occasional single loose stool still isn’t a diarrhea. Unripe fruits, green potatoes, spicy or hot food may all irritate the bowel. Insufficiently cooked or chewed food, a heavy sugary or fatty meal may be hard to digest. Wrong food combinations, like meat with sugar, may result in a loose stool. Food which is psychically rejected, after ingesting, might flow through the intestine quickly. Caffeine stimulates peristalsis, as can strong emotions like fear.

Find the Cause of Diarrhea from Symptoms

In this article, typical symptoms are paralleled with common causes of diarrhea. The cause can be also found by tests for diarrhea.

Causes of Diarrhea in Newborns

Newborn normally poops 8-10 times a day.

• fever, vomiting, diarrhea: Rotavirus, rarely other microbes;
• mild diarrhea: overfeeding, neonatal drug withdrawal;
• skin rash, strain to vomiting (gagging), irritability, diarrhea: allergy to cow’s milk or soy formula;
• diarrhea in first 3 days of life: congenital diseases of liver, pancreas, biliary tract, small or large intestine.

Diarrhea Tests  

The cause of diarrhea can be determined from diarrhea symptoms, or by below diarrhea tests:

• stool tests;
• blood tests;
• urine tests;
• neurological tests;
• food allergy and intolerance tests; 
• absorption tests;
• abdominal ultrasound, endoscopic ultrasound, CT, X-ray with barium, plain abdominal X-ray, abdominal arteriography, HIDA scan, ERCP and MRCP;
• colonoscopy, EGD, capsule endoscopy, double baloon enteroscopy;
• Octreoscan.

Stool Tests In Diarrhea

Stool tests are done in chronic or heavy acute diarrhea and may include:

• Stool culture can show bacteria, causing diarrhea. Clostridium difficile toxin test is recommended in antibiotic associated diarrhea. For diagnosis of some rare bacteria, like Vibrio cholerae, separate tests may be required. Ova and parasites (O&P) test is recommended when diarrhea lasts more than a week. Specific antigen tests for giardia, cryptosporidium, E. histolytica, Helycobacter pylori, or Rotavirus also exist. False positive results of stool culture are from contamination of stool sample with urine or blood, or due to more than an hour passed between sample taking and testing. False negative results may be from antibiotics, laxatives, antidiarrheal drugs, or recent barium or x-ray investigation.
• Fecal occult blood test (FOBT) should be done when intestinal bleeding is suspected (after hemorrhoids, anal fissure, menstruation, and urinary bleeding are excluded). Bloody diarrhea, or diarrhea with a hidden blood may appear in heavy bacterial or parasitic infection, inflammatory bowel disease, and in diverticulitis. Other causes of bloody diarrhea are rare. Stool guaiac test (e.g. Hemoccult) - may detect daily blood loss of about 10 ml (1). Positive test confirms presence of the blood in the stool, but not its origin. Negative result means, that no blood was in the stool during the testing period, so additional samples at different occasions may be required. Three days before the test, red meat, and food which contains blood have to be avoided to prevent false positive results, and radishes, horseradish, turnips, cauliflower, uncooked broccoli, figs, melon, citrus fruits, and vit C supplements have to be avoided to prevent false negative results. Test should not be done in bleeding hemorrhoids, urinary bleeding, or during the menstruation. Five samples from each of three consecutive stools have to be taken. Immunochemical test - iFOBT (e.g. HemSelect) uses antibodies which react with human hemoglobin. The test may detects smaller amount of blood (50 µg/g stool) than guaiac test, but only from lower GI tract, not from the stomach or above (32). No dietary or drug restrictions are needed before the test; one sample from one or two stools is required. Both guaiac and immunochemical test kits are available in pharmacies without prescription, but testing by a lab or doctor is more reliable.
• WBC stool test. White blood cells in the stool may be found in severe bacterial infection, Crohn’s disease or ulcerative colitis.
• Fecal proteins. Lactoferrin is released from leukocytes, and it can be detected in stool in 5 minutes. Increased lactoferrin is a sign of inflammation, so it is used in acute diarrhea to distuinguish between mild viral or parasitic infection (negative) and invasive bacteria (positive), and in chronic diarrhea to distinguish between IBS (negative) and IBD (positive). In later case lactoferrin test was found to be 86% sensitive and 100% specific (26,27). Calprotein is another leukocyte protein, excreted in stool, which correlates with activity of IBD (29). Fecal A1AT test detects serum protein alpha1-antitrypsin in the stool in the protein losing enteropathy (PLE). Radionuclide labeled proteins, injected into a vein, and then appearing in the stool, also speak for PLE. Tests for proteins, excreted in colorectal cancer, are still in the research phase. Protein CD23 was found in the stool of patients with a food allergy (31). 
• Fecal IgA antibodies may be found in certain food allergies (to milk, egg, soy). In one clinical trial, IgA antigliadin antibodies in the stool were found in only 30% of patients with celiac disease, so they were considered as useless for diagnosis (2).

Definition of Acute Diarrhea

Acute (from lat. acutus = sharp, pointed) diarrhea lasts less than 3 weeks (1).

Causes of Acute Diarrhea

A) Acute Infectious Diarrhea:

• Bacterial Diarrhea;
• Parasitic Diarrhea;
• Viral Diarrhea.

B) Acute Non-infectious Diarrhea:

• Food Allergies;
• Diarrhea After Eating;
• Ciguatera and Scombroid Fish Poisoning;
• Mushrooms, Poisonous Plants, Pesticides;
• Heavy Metals Poisoning;
• Antibiotic-Associated Diarrhea;
• Medications, Chemotherapy and Irradiation;
• Psychic Stress;
• Runner’s Diarrhea;
• Diarrhea in Pregnancy.

Causes of Chronic (Constant) Diarrhea.

Definition of Chronic Diarrhea

Diarrhea is considered as chronic, when it lasts for more than 3 weeks.

Main Causes of Chronic Diarrhea

Unlike acute diarrhea, chronic diarrhea is mostly of non-infectious origin.

• Irritable Bowel Syndrome (IBS) ;
• Inflammatory Bowel Disease (IBD);
• Lactose Intolerance;
• Celiac Disease;
• Toddler’s Diarrhea (Dietary Fructose Intolerance - DFI);
• Liver, Gallbladder, Pancreatic Disease;
• Diverticulitis;
• Food Allergies;
• Small Intestinal Bacterial Overgrowth (SIBO);
• Short Bowel Syndrome;
• Diabetes;
• Alcoholism;
• Malnutrition;
• Medications.

Less common causes of chronic diarrhea  are diabetes, ischemic and collagenous colitis, systemic sclerosis, hyperthyroidism, Addison’s disease, uremia, chronic infection/poisoning, AIDS, bowel surgery, inborn diseases, and Brainerd diarrhea.

Irritable Bowel Syndrome (IBS, Spastic Colon)

Chronic diarrhea or constipation or both, appearing in people under 40 years of age with no underlying bowel disease, no bleeding or weight loss, are the main characteristics of irritable bowel syndrome. Symptoms (diarrhea, constipation, bloating, gas, painful abdominal cramps, or urgency) typically appear after the meal or stress event, and are relieved with a bowel movement. ‘Functional diarrhea‘, also called painless or nervous diarrhea, is like IBS, but without abdominal pain.