Metabolic food disorders are one example of a food intolerance and are NOT the result of a disorder of the immune system. Metabolic food disorders result from a genetically-inherited defect in the ability to metabolize a food component or a genetically-inherited sensitivity to a food component that affects some critical metabolic process. Lactose intolerance and favism can serve as examples. Lactose intolerance occurs because of an inherited deficiency of the enzyme, β-galactosidase, in the intestinal mucosa. Favism results from an inherited deficiency in the enzyme, glucose-6-phosphate dehydrogenase, in the erythrocytes, which causes a heightened sensitivity to several naturally occurring oxidant compounds found in fava beans.

Lactose Intolerance

Intolerance to milk and other dairy products can occur through at least two distinct routes. Milk allergy is an IgE-mediated allergic reaction resulting in the rapid onset of a variety of symptoms upon ingestion of milk often even in tiny amounts. Lactose intolerance is a form of food intolerance, a metabolic food disorder, associated with a deficiency of the enzyme, β-galactosidase or lactase, in the intestinal mucosa. The symptoms of lactose intolerance occur on a slightly delayed basis by comparison to milk allergy. Importantly, lactose-intolerant consumers can often tolerate some milk in their diets without harmful effect.

The deficiency of β-galactosidase in the small intestine means that lactose, the primary sugar in milk and milk products, cannot be metabolized into its component monosaccharides, galactose and glucose. In contrast to the monosaccharides, the undigested lactose cannot be absorbed across the small intestinal epithelium. Instead, the undigested lactose thus passes into the colon (large intestine), where resident bacteria metabolize the lactose into CO2, H2, and H2O. The characteristic symptoms of lactose intolerance are bloating, flatulence, abdominal cramping, and frothy diarrhea.

Sources and Occurrence in Foods

Lactose, the principal sugar in milk and milk products, is a disaccharide, 4'-(β-D-galacto-pyranoside)-D-glucopyranose (find a structure for lactose and insert). Lactose is quite unique and is found exclusively in milk and milk products. Appreciable amounts of lactose are present in many dairy products such as milk, ice cream, cottage cheese, and yogurt. Hard cheeses contain only small amounts of lactose.


The prevalence of lactose intolerance is quite high on a worldwide basis. Lactose intolerance occurs with high frequency among black Americans, Native Americans, Hispanics, Asians, Jews, and Arabs, affecting as many as 60-90% of individuals in such groups. By contrast, the prevalence is much lower among North American Caucasians at about 6-12%. Most infants possess high activity levels of β-galactosidase at birth. However, beyond the period of infancy, people in the ethnic groups mentioned slowly lose up to 90% of their intestinal β-galactosidase activity. This normal pattern of loss of β-galactosidase activity is transmitted by a recessive gene and should be considered a normal physiologic event. High β-galactosidase levels persist into adulthood in a few ethnic populations such as Caucasians presumably as an adaptation to the widespread historical use of dairy products in these cultures. β-Galactosidase persistence is inherited as an autosomal dominant characteristic. While genuine lactose intolerance affects a considerable number of individuals on a worldwide basis, 15-30% of self-diagnosed, lactose-intolerant individuals in the U.S. have satisfactory levels of β-galactosidase and thus should not display the symptoms of lactose intolerance upon the ingestion of dairy products.

Congenital lactose intolerance is the complete absence of β-galactosidase at birth. Obviously, this condition leads to profound lactose intolerance even in infancy. However, the prevalence of this condition is quite low.

Minimal Eliciting Dose and Management

The usual treatment for lactose intolerance is the avoidance of dairy products containing lactose. The symptoms of lactose intolerance can be avoided by the implementation of a dairy product avoidance diet. In contrast to IgE-mediated food allergies, lactose-intolerant individuals can usually tolerate some amount of lactose in their diets. The degree of tolerance does vary among lactose-intolerant individuals. The majority of lactose-intolerant individuals will develop only trivial symptoms following the consumption of 12 g of lactose, an amount equivalent to one cup of milk. The frequency and severity of symptoms increase as the lactose dose exceeds 12 g. Lactose ingested with a meal containing high amounts of solids or fat is better tolerated than a similar amount of lactose in fluid milk. Most adults consume less than 25 g of lactose per day, whereas infants commonly consume >50 g per day. On a body weight basis, infants ingest significantly greater amounts of lactose than adults.

Individuals with lactose intolerance appear to tolerate yogurt and acidophilus milk better than other dairy products despite the fact that these products contain appreciable amounts of lactose. Apparently, these fermented products have inherent lactase activity which is partially able to survive digestive processes and assist with the metabolism of lactose in the small intestine. The emergence of lactose-hydrolyzed dairy products onto the marketplace in recent years provides lactose-intolerant individuals with another means to control their reactions.

Lactose-intolerant individuals should be encouraged to ingest as much dairy product as they are able to tolerate. Dairy products provide 75% of the calcium intake in U.S. diets so the implementation of dairy product avoidance diets from childhood can place individuals at increased risk for postmenopausal osteoporosis. Calcium supplements including calcium-fortified fruit juice can be important for individuals with lactose intolerance.

Lactose intolerance is not a severe illness with generally mild symptoms confined to the gastrointestinal tract. Symptom severity can vary from one individual to another dependent upon β-galactosidase activity, gastrointestinal transit time, lactose load, and colonic fermentation.

Overall, the risk posed by lactose to lactose-intolerant individuals is much less than the risk posed by allergenic foods to individuals with IgE-mediated food allergies. While lactose intolerance may affect a larger number of individuals, the symptoms are, in general, much more mild, and the tolerance for lactose in the diet equates to fewer problems in the implementation of a safe and effective avoidance diet.


Favism involves an intolerance to the ingestion of fava beans or the inhalation of pollen from the Vicia faba plant. Sensitive individuals suffer from acute hemolytic anemia upon exposure with characteristic symptoms that include pallor, fatigue, dyspnea, nausea, abdominal and/or back pain, fever, and chills. Rarely, hemoglobinuria, jaundice, and renal failure will occur. The onset time following ingestion is quite rapid, usually occurring in 5-24 hours. Recovery is prompt and spontaneous if no further exposure occurs. In addition to ingestion, favism can occur when the Vicia faba plant is in bloom, causing elevated levels of airborne pollen.

Individuals susceptible to favism are those with an inherited deficiency of the enzyme, glucose-6-phosphate dehydrogenase (G6PDH), in their red blood cells (erythrocytes). The diagnosis of G6PDH deficiency is made through an assay for enzymatic activity of G6PDH in isolated red blood cells. G6PDH is a critical enzyme in erythrocytes, where it is essential to maintain adequate levels of the reduced form of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH); GSH and NADPH prevent oxidative damage to the cells. Thus, the red blood cells of individuals with G6PDH deficiency are more susceptible to oxidative damage. Fava beans contain several naturally occurring oxidants, including vicine and convicine, which are able to damage the erythrocytes of G6PDH-deficient individuals. G6PDH deficiency is the most common inherited enzymatic defect in humans on a worldwide basis affecting more than 100 million people. G6PDH deficiency occurs with the highest frequency among Oriental Jewish communities in Israel, Sardinians, Cypriot Greeks, American blacks, and certain African populations. The trait is virtually non-existent in northern European nations, North American Indians, and Eskimos.

Favism occurs most frequently in areas where the plant grows and the crop is harvested and sold in local markets. Favism generally occurs when the plant is blooming and when the fava beans are sold in the market. Thus, favism occurs primarily in the Mediterranean area, the Middle East, China, and Bulgaria, because the genetic trait is fairly prevalent in that region and fava beans are frequently consumed in that region as well. Favism is almost unheard of in the U.S. because fava beans are rarely eaten and the plant is rarely grown; G6PDH deficiency certain does occur in the U.S. so favism could occur here if the exposure situation were to change. Obviously, susceptible individuals can avoid favism by avoiding the ingestion of fava beans and/or the inhalation of the plant pollen.