ter 5 ounces of ethanol may have been related to an anesthetic effect which might have masked earlier recognition of anginal pain by the subjects. These data indicate that there is really no useful purpose for the prescription of ethanol
for people with angina pectoris and coronary artery disease. 0 1. J. Orlando, W.S. Aronow, J. Cassidy and R . Prakash: Effect of Ethanol on Angina Pectoris. Ann. Int. Med. 84: 652-655, 1976
THE LACTOSE INTOLERANCE TEST AND MILK CONSUMPTION Many children who show symptoms of lactose intolerance in a standard lactose tolerance test (LTT) can and do consume moderate amounts of milk without significant gastrointestinal upset. The LTT probably overemphasizes the problem of lactose deficiency in a population. Key Words: lactose intolerance, milk intolerance, children
In lactose intolerance the enzyme that hydrolyzes the carbohydrate, lactose, in milk into glucose and galactose is present in low concentration or is inactive. Thus lactose, passed to the colon unaltered, increases gut fluid volume. Bacteria in the colon ierment the lactose and a variety of gastrointestinal symptoms (diarrhea, flatulence, abdominal cramps and bloating) can occur with varying severity. There are considerable data showing a significant difference in lactose tolerance of people throughout the world.’>* Like most mammals, human infants have characteristically high lactase activity which decreases progressively after three or four years of age.3 This drop is not as extensive in Caucasian as it is in Oriental and Negroid populations. Only 5 to 15 percent of Caucasian adults have low lactase activity compared with 60 to 90 percent of the noncaucasian p o p ~ l a t i o n .It~ has been suggested that since the great majority of the world’s adults have low lactase activity that this level of activity is normal and that genetic selection may account for the relatively high lactase activity of Caucasian adults. Possibly the appearance in antiquity of milkable domesticated animals in regions such as Northern Europe led to continued human consumption of milk after weaning and may have necessitated the genetic adaptation of higher lactase activity throughout life. Simoons,l in an extensive survey of lactose intolerance and cultural and socioeconomic conditions throughout the 302 NUTRITION REVIEWS I VOL. 34, NO. 10 I OCTOBER 1976
world, observed that no indigenous human group with a low incidence of lactose intolerance has been discovered in traditionally nonmilking areas. The extensiveness of primary lactose intolerance caused special concern in the United States as well as in developing countries where large-scale public health programs encouraged the distribution of milk, since many of the milk recipients, being noncaucasian, are prone to lactose intolerance. Garza and Scrimshaw5 recently studied 99 children, ranging in age from four to nine years, who were all healthy and free of any diseases which could cause a temporary lactase deficiency. Thirty children, 20 black and ten white, were fed 12, 18 and 25 g lactose in a peanut butter sandwich (PBL) corresponding to the amount present in 8,12 and 16 ounces respectively of whole milk and with the same fat to lactose ratio. The remainder of the children received the same levels of lactose as whole milk. Symptoms were monitored for 24 hours following each dose. If definite symptoms developed they were not fed the next higher lactose level. When mild symptoms persisted or worsened at the next level, the child was rated lactose intolerant at the lower level of lactose intake. Standard lactose tolerance tests were administered when no symptoms were observed at the highest level, 24 g, of lactose. Both blood glucose level and intolerance symptoms were monitored for four hours. No symptoms of lactose intolerance were found at any level of lactose intake from PBL or milk in the white children of any age. With
the black children, symptom prevalence increased with the level of lactose, ranging from 0 to 10 percent with 12 g lactose to 40 percent with the highest dosage as PBL. The black children were more tolerant of lactose administered with milk. None of the children was intolerant of the lowest dosage of lactose and 8 to 20 percent could not tolerate 24 g lactose as milk. Lactose intolerance was more common in the nine year old black subjects compared with the four year old subjects. Age apparently had no bearing on the prevalence of lactose intolerance in lactose tolerant white subjects of the same age groups. It should be noted that none of the children had any difficulty tolerating lactose provided by 8 ounces of milk, and intolerance to the 12 ounces of milk was very mild. All the children went on to drink 16 ounces of milk the third day. Half of the children with symptoms at that level reported the symptoms were mild, the others moderate. The children stated that drinking 16 ounces of milk at one time was an unusual practice, thus it may be that most children consumed milk at a rate providing lactose levels easily tolerated by them. Significantly more children were indicated to be lactose intolerant using a standard lactose tolerance test which involves consumption of the equivalent of lactose present in a quart of milk. Combining the cases reporting symptoms from one of the three levels of milk and/or the PBL mixture with the cases reporting symptoms after the lactose tolerance test, the lactose intolerance of Garza and Scrimshaw’s subjects were as foliows: of the blacks age four and five the percent of lactose intolerance jumped to 11 percent, ages six and seven to 50 percent and ages eight and nine to 72 percent; of the whites no intolerance was reported in ages four through seven, but 20 percent of eight and nine year olds were lactose intolerant. Clearly these results present a picture of lactose intolerance as being more extensive than that indicated from consumption of the more reasonable dietary lactose levels used in PBL and milk studies. In addition, there was some discrepancy in lactose intolerance as reported by the maxi-
mum blood glucose levels and as reported by the occurrence of symptoms with the lactose tolerance test dose. Of the 82 children given the lactose tolerance test, 9 percent who had normal blood glucose elevations indicating lactose tolerance, reported symptoms of lactose intolerance. Thirty-three percent of the children with a blood glucose elevation lower than 20 mg per 100 ml, indicating lactose intolerance, did not display any symptoms. This raises the question as to whether the blood glucose level is truly an indicator of lactose intolerance. There is also a risk in the subjective evaluation of symptoms. Do they actually exist, what is their severity, and how much is due to factors other than lactose consumption? It would seem that the extrapolation of results of the lactose tolerance test to the general population unnecessarily magnifies the problem of lactose intolerance in a practical milk program. Many people prone to lactose intolerance appear to be able to consume nutritionally significant levels of milk short of the test dose used in lactose tolerance tests without the development of symptoms. They apparently have sufficient although low levels of lactase to hydrolyze lactose in moderate amounts of milk. This gradation of lactase activity must be taken into account when evaluating a population for the purposes of a milk supplementation program. Comparison of usual milk intake habits with the prevalence of lactose intolerance showed significant correlation only with black children eight and nine years old. They drank less milk than the white children of the same age and had a higher prevalence of lactose intolerance. There was no significant difference, however, in the amount of milk consumed during a normal day by the black lactose tolerant and lactose intolerant children at any age, nor between the amount of milk consumed by black and white children, six and seven years old. These data do not support suggestions that low milk consumption may be influenced by lactose intolerance.6 Operational lactose intolerance may be inadequate in predicting milk rejection and invalid in the decision as to whether or not milk supplementation of a diet will be accepted by a population. 0 NUTRITION REVIEWS I VOL. 34, NO. 10 I OCTOBER 1976 303
F.J. Simoons: New Light on Ethnic Differences in Adult Lactose Intolerance. Am. J. Dig. Dis. 18: 595-61 1 , 1973 C.W. Woodruff: Milk Intolerances. Nutrition Reviews 34:33-37, 1976 American Academy of Pediatrics, Committee
on Nutrition: Should Milk Drinking by Children be Discouraged? Pediatrics 53: 576-582, 1974 Committee on International Nutrition Programs: Background Information on Lactose and
Milk Intolerance. Nutrition Reviews 30: 175-176, 1972 5. C. Garza and N.S. Scrimshaw: Relationship of Lactose Intolerance to Milk Intolerance in Young Children. Am. J. Clin. Nutrition 29: 192196, 1976 6. D.M. Paige, T.M. Bayless and G.G. Graham: Milk Programs: Helpful or Harmful to Negro Children? Am. J. Pub. Health 62: 1486-1488. 1972
SERUM FERRlTlN AND EARLY HEMOCHROMATOSIS The value of serum ferritin levels in the diagnosis of early hemochromatosis in the relatives of established cases is reviewed in light of recent work. Key Words: hemochromatosis, ferritin, iron absorp-
tion The development of a sensitive immunoradiometric assay for ferritinl has helped open up research in the field of iron metabolism. A salient result of such research has been the postulate that serum ferritin is directly proportional to total iron stores. Thus serum ferritin is low in iron deficiency,Z falls with serial venesection of normal individuals,3 is high in patients with hemosiderosis and hemochromatosis2 and similarly falls in the latter group as they undergo therapeutic venesection . 4 Furthermore there is a correlation between serum ferritin and the number of blood transfusions which have produced the hemosiderosis found in treated aplastic anemia2and in multitransfused patients with thalassemia major. Serum ferritin correlates with the iron content of liver.5 Evidence that serum ferritin and total iron stores do not always change pari passu has been accumulating recently. The ‘anemia of chronic disorders’ delineated by Cartwright and Lee6 is characterized by a hypochromic or normochromic anemia, low serum iron and iron-binding capacity levels, and an increase in reticuloendothelial iron stores readily discernible on iron staining of aspirated bone marrow. A reticuloendothelial block to the release of iron is postulated although the cause for this is obscure. Supranormal serum ferritin levels have been found in rheumatoid arthritis7 and Hodgkin’s disease8 in which this type 304 NUTRlTlON REVIEWS / VOL. 34,
NO.10 /OCTOBER 1976
of anemia may be present and may be due to overspill of ferritin from the overloaded reticuloendothelial cells. In liver disease, both acute and chronic, high serum ferritin levels were commonly found.g The correlation of these raised levels with an empirical index derived from the product of the serum transaminase and the hepatic iron concentration was better than with either factor alone. This suggested to the authors that the level of serum ferritin was dependent both on the degree of hepatocellular damage and the level of pre-existing iron stores. High ferritin levels have also been found in leukemia, both acute myeloblastice and acute lymphocytic.10 It has also been suggested that at least in the former, serum ferritin is related to increased production of apoferritin by the leukemic cells.ll The doubts that have been cast on the universal validity of the serum ferritin level as an estimate of total body iron stores have further been reinforced by a recent paper by Wands and his co-workers.12 This paper reports a study of the two families of separate patients with hemochromatosis. Its findings are of both clinical importance and of relevance to current theories on iron absorption and metabolism. The two index patients both presented with hematemesis due to esophageal varices, had diabetes mellitus and cirrhotic livers providing biopsies consistent with hemochromatosis. The first case, who died of a primary hepatoma, had a large family. The members of this family and the small family of the second case were subjected to intensive examination. In
for people with angina pectoris and coronary artery disease. 0 1. J. Orlando, W.S. Aronow, J. Cassidy and R . Prakash: Effect of Ethanol on Angina Pectoris. Ann. Int. Med. 84: 652-655, 1976
THE LACTOSE INTOLERANCE TEST AND MILK CONSUMPTION Many children who show symptoms of lactose intolerance in a standard lactose tolerance test (LTT) can and do consume moderate amounts of milk without significant gastrointestinal upset. The LTT probably overemphasizes the problem of lactose deficiency in a population. Key Words: lactose intolerance, milk intolerance, children
In lactose intolerance the enzyme that hydrolyzes the carbohydrate, lactose, in milk into glucose and galactose is present in low concentration or is inactive. Thus lactose, passed to the colon unaltered, increases gut fluid volume. Bacteria in the colon ierment the lactose and a variety of gastrointestinal symptoms (diarrhea, flatulence, abdominal cramps and bloating) can occur with varying severity. There are considerable data showing a significant difference in lactose tolerance of people throughout the world.’>* Like most mammals, human infants have characteristically high lactase activity which decreases progressively after three or four years of age.3 This drop is not as extensive in Caucasian as it is in Oriental and Negroid populations. Only 5 to 15 percent of Caucasian adults have low lactase activity compared with 60 to 90 percent of the noncaucasian p o p ~ l a t i o n .It~ has been suggested that since the great majority of the world’s adults have low lactase activity that this level of activity is normal and that genetic selection may account for the relatively high lactase activity of Caucasian adults. Possibly the appearance in antiquity of milkable domesticated animals in regions such as Northern Europe led to continued human consumption of milk after weaning and may have necessitated the genetic adaptation of higher lactase activity throughout life. Simoons,l in an extensive survey of lactose intolerance and cultural and socioeconomic conditions throughout the 302 NUTRITION REVIEWS I VOL. 34, NO. 10 I OCTOBER 1976
world, observed that no indigenous human group with a low incidence of lactose intolerance has been discovered in traditionally nonmilking areas. The extensiveness of primary lactose intolerance caused special concern in the United States as well as in developing countries where large-scale public health programs encouraged the distribution of milk, since many of the milk recipients, being noncaucasian, are prone to lactose intolerance. Garza and Scrimshaw5 recently studied 99 children, ranging in age from four to nine years, who were all healthy and free of any diseases which could cause a temporary lactase deficiency. Thirty children, 20 black and ten white, were fed 12, 18 and 25 g lactose in a peanut butter sandwich (PBL) corresponding to the amount present in 8,12 and 16 ounces respectively of whole milk and with the same fat to lactose ratio. The remainder of the children received the same levels of lactose as whole milk. Symptoms were monitored for 24 hours following each dose. If definite symptoms developed they were not fed the next higher lactose level. When mild symptoms persisted or worsened at the next level, the child was rated lactose intolerant at the lower level of lactose intake. Standard lactose tolerance tests were administered when no symptoms were observed at the highest level, 24 g, of lactose. Both blood glucose level and intolerance symptoms were monitored for four hours. No symptoms of lactose intolerance were found at any level of lactose intake from PBL or milk in the white children of any age. With
the black children, symptom prevalence increased with the level of lactose, ranging from 0 to 10 percent with 12 g lactose to 40 percent with the highest dosage as PBL. The black children were more tolerant of lactose administered with milk. None of the children was intolerant of the lowest dosage of lactose and 8 to 20 percent could not tolerate 24 g lactose as milk. Lactose intolerance was more common in the nine year old black subjects compared with the four year old subjects. Age apparently had no bearing on the prevalence of lactose intolerance in lactose tolerant white subjects of the same age groups. It should be noted that none of the children had any difficulty tolerating lactose provided by 8 ounces of milk, and intolerance to the 12 ounces of milk was very mild. All the children went on to drink 16 ounces of milk the third day. Half of the children with symptoms at that level reported the symptoms were mild, the others moderate. The children stated that drinking 16 ounces of milk at one time was an unusual practice, thus it may be that most children consumed milk at a rate providing lactose levels easily tolerated by them. Significantly more children were indicated to be lactose intolerant using a standard lactose tolerance test which involves consumption of the equivalent of lactose present in a quart of milk. Combining the cases reporting symptoms from one of the three levels of milk and/or the PBL mixture with the cases reporting symptoms after the lactose tolerance test, the lactose intolerance of Garza and Scrimshaw’s subjects were as foliows: of the blacks age four and five the percent of lactose intolerance jumped to 11 percent, ages six and seven to 50 percent and ages eight and nine to 72 percent; of the whites no intolerance was reported in ages four through seven, but 20 percent of eight and nine year olds were lactose intolerant. Clearly these results present a picture of lactose intolerance as being more extensive than that indicated from consumption of the more reasonable dietary lactose levels used in PBL and milk studies. In addition, there was some discrepancy in lactose intolerance as reported by the maxi-
mum blood glucose levels and as reported by the occurrence of symptoms with the lactose tolerance test dose. Of the 82 children given the lactose tolerance test, 9 percent who had normal blood glucose elevations indicating lactose tolerance, reported symptoms of lactose intolerance. Thirty-three percent of the children with a blood glucose elevation lower than 20 mg per 100 ml, indicating lactose intolerance, did not display any symptoms. This raises the question as to whether the blood glucose level is truly an indicator of lactose intolerance. There is also a risk in the subjective evaluation of symptoms. Do they actually exist, what is their severity, and how much is due to factors other than lactose consumption? It would seem that the extrapolation of results of the lactose tolerance test to the general population unnecessarily magnifies the problem of lactose intolerance in a practical milk program. Many people prone to lactose intolerance appear to be able to consume nutritionally significant levels of milk short of the test dose used in lactose tolerance tests without the development of symptoms. They apparently have sufficient although low levels of lactase to hydrolyze lactose in moderate amounts of milk. This gradation of lactase activity must be taken into account when evaluating a population for the purposes of a milk supplementation program. Comparison of usual milk intake habits with the prevalence of lactose intolerance showed significant correlation only with black children eight and nine years old. They drank less milk than the white children of the same age and had a higher prevalence of lactose intolerance. There was no significant difference, however, in the amount of milk consumed during a normal day by the black lactose tolerant and lactose intolerant children at any age, nor between the amount of milk consumed by black and white children, six and seven years old. These data do not support suggestions that low milk consumption may be influenced by lactose intolerance.6 Operational lactose intolerance may be inadequate in predicting milk rejection and invalid in the decision as to whether or not milk supplementation of a diet will be accepted by a population. 0 NUTRITION REVIEWS I VOL. 34, NO. 10 I OCTOBER 1976 303
F.J. Simoons: New Light on Ethnic Differences in Adult Lactose Intolerance. Am. J. Dig. Dis. 18: 595-61 1 , 1973 C.W. Woodruff: Milk Intolerances. Nutrition Reviews 34:33-37, 1976 American Academy of Pediatrics, Committee
on Nutrition: Should Milk Drinking by Children be Discouraged? Pediatrics 53: 576-582, 1974 Committee on International Nutrition Programs: Background Information on Lactose and
Milk Intolerance. Nutrition Reviews 30: 175-176, 1972 5. C. Garza and N.S. Scrimshaw: Relationship of Lactose Intolerance to Milk Intolerance in Young Children. Am. J. Clin. Nutrition 29: 192196, 1976 6. D.M. Paige, T.M. Bayless and G.G. Graham: Milk Programs: Helpful or Harmful to Negro Children? Am. J. Pub. Health 62: 1486-1488. 1972
SERUM FERRlTlN AND EARLY HEMOCHROMATOSIS The value of serum ferritin levels in the diagnosis of early hemochromatosis in the relatives of established cases is reviewed in light of recent work. Key Words: hemochromatosis, ferritin, iron absorp-
tion The development of a sensitive immunoradiometric assay for ferritinl has helped open up research in the field of iron metabolism. A salient result of such research has been the postulate that serum ferritin is directly proportional to total iron stores. Thus serum ferritin is low in iron deficiency,Z falls with serial venesection of normal individuals,3 is high in patients with hemosiderosis and hemochromatosis2 and similarly falls in the latter group as they undergo therapeutic venesection . 4 Furthermore there is a correlation between serum ferritin and the number of blood transfusions which have produced the hemosiderosis found in treated aplastic anemia2and in multitransfused patients with thalassemia major. Serum ferritin correlates with the iron content of liver.5 Evidence that serum ferritin and total iron stores do not always change pari passu has been accumulating recently. The ‘anemia of chronic disorders’ delineated by Cartwright and Lee6 is characterized by a hypochromic or normochromic anemia, low serum iron and iron-binding capacity levels, and an increase in reticuloendothelial iron stores readily discernible on iron staining of aspirated bone marrow. A reticuloendothelial block to the release of iron is postulated although the cause for this is obscure. Supranormal serum ferritin levels have been found in rheumatoid arthritis7 and Hodgkin’s disease8 in which this type 304 NUTRlTlON REVIEWS / VOL. 34,
NO.10 /OCTOBER 1976
of anemia may be present and may be due to overspill of ferritin from the overloaded reticuloendothelial cells. In liver disease, both acute and chronic, high serum ferritin levels were commonly found.g The correlation of these raised levels with an empirical index derived from the product of the serum transaminase and the hepatic iron concentration was better than with either factor alone. This suggested to the authors that the level of serum ferritin was dependent both on the degree of hepatocellular damage and the level of pre-existing iron stores. High ferritin levels have also been found in leukemia, both acute myeloblastice and acute lymphocytic.10 It has also been suggested that at least in the former, serum ferritin is related to increased production of apoferritin by the leukemic cells.ll The doubts that have been cast on the universal validity of the serum ferritin level as an estimate of total body iron stores have further been reinforced by a recent paper by Wands and his co-workers.12 This paper reports a study of the two families of separate patients with hemochromatosis. Its findings are of both clinical importance and of relevance to current theories on iron absorption and metabolism. The two index patients both presented with hematemesis due to esophageal varices, had diabetes mellitus and cirrhotic livers providing biopsies consistent with hemochromatosis. The first case, who died of a primary hepatoma, had a large family. The members of this family and the small family of the second case were subjected to intensive examination. In
