Relationship of milk intolerance
lactose intolerance in young children”2
Cutberlo
Nevin
Garza,’
M.D.,
and
ABSTRACT
The
test was compared white
children.
old, to
and
72%
240
ml
frequency young
prevalence
lactose No
and
children
than
the
ingestion
black
of 2 g lactose/kg
recommend 192
that
the
term
The American
as revealed
by the standard
lactose Journal
Am.
.
intolerance Nutrition
The
50 g)was J. Clin.
limiting
nor between blood
lactose
unreliable
no child
did
milk
tolerance
intakes
response an
29: 192’- 196,
was
intolerant
suggest milk
milk
children
as
not
existing the
black
glucose
Nuir.
milk
between
8- to 9-year-old
did.
yet
of
for
found
children,
(maximum
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
amounts
be a reason were
However,
children
of Clinical
to be lactose-intolerant,
greater
differences
to lactose.
.
to might
The accumulation of evidence that there is an age-dependent increase in the prevalence of intolerance to a large test dose of lactose in many of the world’s populations (1 -4) has raised doubts about encouraging milk consumption by such individuals. The traditional reliance on milk in supplementary feeding programs for children makes the issue important. In 1972 an international group (5) concluded that it would be highly inappropriate. . . to discourage programs to improve milk supplies...” on the basis of evidence then available. A similar statement was issued by the Food and Nutrition Board (6) and the American Academy of Pediatrics, Committee on Nutrition (7). However, these groups and others (8-10) have also emphasized the need for further investigation into the relationship between milk intolerance and lactose intolerance on the basis of the widespread occurrence of lactose intolerance. The controversy in the United States has centered on the provision of milk to black, Spanish-American, and other children with a high frequency of lactose intolerance. It has been characterized by unwarranted extrapolations and inconsistent terminology. Often the terms lactose intolerance, lactase deficiency, lactose malabsorption, and milk intolerance have been used interchangeably. We “.
found
lactose-intolerant white
response
were
intolerance
in Boston.
8- to 9-year-old
symptomatic
M.D.
intolerance
responses
significant
black milk
old
Symptom
lactose-tolerant and white
of lactose
8 to 9 years
milk.
of primary children.
Ph.D.,
with the occurrence of intolerance to graded amounts of milk in 69 black and 30 Of the black children studied, 11% of those 4 to 5 years old, 50% of those 6 to 7 years
of those
of
S. Scrimshaw,’
to
that
the
programs
intakes
of
for black
of 6- and 7-year-old
drank
significantly
less
at 0, 20, and 45 mm indicator
of
an
after
individual’s
1976.
be applied only when gastrointestinal symptoms, such as flatulence, bloating, abdominal cramps, or loose stools occur in response to the ingestion of a test dose of lactose (2 g/kg body weight), up to a maximum of 50 g. This sometimes occurs in the presence of blood glucose responses of >20 mg/lOO ml to a standard lactose tolerance test dose. Furthermore, distinctions should be made among the types of lactose intolerance. The intolerance may be caused by 1) congenital absence of lactase, a rare condition; 2) an apparently normal developmental decrease in the level of lactase-primary lactose intolerance-and 3) damage to the intestinal mucosa by any of a variety of agents-viral, bacterial, gluten, and the like-leading to secondary lactose intolerance. The term lactase deficiency should be applied only to secondary lactose intolerance, because primary lactose intolerance appears to be normal for other animal species and a majority
‘With
financial
Council. 2 Department
assistance
of
Nutrition
from
and
The
Food
National
Science
Dairy
Publi-
cation
2688. Predoctoral Fellow, Department of Nutrition and Food Science, Massachusetts Institute of Technology. Professor of Human Nutrition and Head, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
29:
FEBRUARY
1976,
pp.192-196.
Printed
in U.S.A.
RELATIONSHIP
OF
LACTOSE
INTOLERANCE
of humans. The term lactose malabsorption should be reserved only for cases where there is a “flat glucose response curve” after a test dose of lactose, with or without symptoms. Moreover, intolerance to small or moderate amounts of milk cannot be predicted from the results of a standard lactose tolerance test because of the large amount of lactose used and the unphysiological manner of its administration (I 1-13). This study in young children compares the prevalence of intolerance to 240, 360, and 480 ml of whole milk, or to the equivalent levels of lactose provided in a lactose-peanut butter mixture (PBL), with the prevalence of primary lactose intolerance revealed by the standard lactose tolerance test. Usual milk intakes and home attitudes toward milk consumption were also investigated. Parents were interviewed for their children’s medical and dietary histories, and their written consent was obtained. Subjects
and
methods
The subjects were 99 healthy age; 69 were black and 30 were Phase
children, white.
4 to 9 years
of
TO
MILK
193
INTOLERANCE
except that the lactose was provided in 240, 360, and 480 ml of whole milk consumed on 3 different days.
Results The percentages of children with positive symptom responses to graded doses of lactose when provided in the PBL mixture are given in Table 1 and the responses to lactose in the various amounts of whole milk are given in Table 2. Based on the respective sample sizes, the probabilities of having failed to find a child intolerant to 240 ml of whole milk range from 0.87 for a hypothetical prevalence of 1%, to 0.10 for a prevalence of 15% for black children 4 to 5 years of age. For black children age 6 to 7, the probability rate was 0.84 to 0.06 for hypothetical prevalences of I and 15%, respectively, and for black children age 8 to 9 the range was 0.81 to 0.10 for hypothetical rates of 1 to 10%, respectively. Milk intolerance was not observed at any level of intake in the white children. Table 3 gives the age-related prevalence of lactose intolerance. Children included in this table had symptoms of intolerance to either the standard dose of lactose given in a water solution or to lesser amounts when provided
I
Thirty children (20 black, 10 white) were provided with 12, 18, and 24 g of lactose in a peanut butter-jelly sandwich on 3 consecutive days. The mixture had a fat to lactose ratio similar to that of whole milk. The children were watched for at least 5 hr after the ingestion of lactose, and their parents were interviewed to learn whether any child developed symptoms while at home for
TABLE Symptom of lactose
the remainder of a 24-hr period. Children developing gastrointestinal symptoms, such as flatulence, bloating, abdominal cramps, or loose stools were not fed the next higher level of lactose unless the symptoms were equivocal, i.e., very mild and difficult to evaluate. In this case either the level was repeated or the next higher was tried. If more marked symptoms were noted at the next higher level, or if the symptoms remained about the same, the child was classified as intolerant to the lower level. When symptoms of intolerance were not observed or reported at the three lower levels, a standard lactose tolerance test was performed in most cases. Two grams of lactose/kg body weight (maximum 50 g) were provided in a 20% water solution to the fasting child. Microcapillary blood
Blacks 6-7 8-9 Whites 67 8-9
samples were obtained from the child’s fingertip at 0, 20, and 45 mm after the oral administration of the lactose solution. Blood glucose was measured using the glucose oxidase method. Again, children were observed for at least 4 hr after the lactose administration.
Age (yr)
I response in peanut
to graded butter
amounts
N
% intolerant tol8g
tol2g
to24g
10 10
0 10
10 30
40 40
7 3
0 0
0 0
0 0
TABLE 2 Symptom response to graded amounts of lactose found in whole milk Age (yr) Blacks 4-5 67 8-9
% intolerant
No. to 12g
to 18g
to24g
13 16 20
0 0 0
0 6 IS
8 12 20
2 9 9
0 0 0
0 0 0
0 0 0
Whites
Phase
2
Sixty-nine this phase.
children (49 black, 20 white) participated The design was similar to that of phase
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
in 1
4-5 67 8-9
GARZA
194 TABLE 3 Age-specific prevalence in children 4 to 9 years Age
Blacks 45 67 89 Whites 45 67 89
of lactose old
AND
intolerance
95
conlidence interval
No.
% intolerant
9 24 29
II 50 72
0046 2771 Sl86
2 14 10
0 0 20
023 257
in either whole milk or the PBL mixture. The lactose-intolerant group includes nine children with positive symptom responses to the PBL mixture or milk and who had no lactose tolerance test because consent could not be obtained, and five children with a blood glucose increase > 20 mg/ 100 ml and marked symptoms after the standard lactose tolerance test dose, but whose blood glucose increase was significantly lower (P < 0.025) than in children with no symptoms. Twenty-one percent of the lactose-intolerant children had positive symptom responses to 18 g oflactose in either whole milk or PBL, and approximately 40% had symptom responses to 24 g of lactose in either whole milk or PBL. Among the 69 black children studied, one 9-year-old child did report symptoms of intolerance at the l2-g level (provided in the PBL mixture). The mother stated that the child complained at home of mild abdominal discomfort. Both the child and the mother were unaware of any adverse response to milk. The next higher level of lactose was tried. Again, no symptoms were observed directly, but the child complained of mild abdominal discomfort at home. Both complaints occurred about 10 hr after the ingestion of lactose. Data were also obtained on the reliability of using blood glucose levels at 0, 20, and 45 mm after the ingestion of a standard test dose of lactose for predicting lactose intolerance. Eighty-two children were given a lactose tolerance test. Nine percent of the 55 with a maximum mg per 100 ml increase in blood glucose of more than 20 had symptoms, and 33% of the 27 having increases of less than 20 mg/lOO ml had no symptoms. Both false positive and false negative rates appear sub-
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
SCRIMSHAW
stantial. However, it must be noted that nine children with symptoms at the lower level of lactose were not given a lactose tolerance test. Had they been tested, the percentage of children with an increase of less than 20 mg/l00 ml and no symptoms would probably have been lower. No differences in milk intake were found between either 6- to 7-year-old or 8- to 9-year-old black lactose-tolerant and lactoseintolerant children. No differences were found between the milk intakes of 6- to 7-year-old black and white children. However, differences between 8- to 9-year-old black and white children were found. When comparisons were made between mothers of lactosetolerant and lactose-intolerant black children, between mothers of lactose-tolerant black children and whites, and between black and white mothers of lactose-tolerant or -intolerant children, none of the apparent differences in milk intake were significant by the x2 test (a 0.05). Similar comparisons between fathers demonstrated no statistically significant differences. The milk intakes of the children and their parents are found in Tables 4, 5, and 6. =
Discussion The controversy children who have lactose-intolerant
over providing milk to a high probability of being rests on the potential of
TABLE 4 Daily milk intake of lactose-tolerant and -intolerant black children A ge
Lactosetolerant
yr
Lactoseintolerant (ml)
(ml)
6-7 8-9
585 570
a Degree
± ±
276 237
of freedom.
555 627
± ±
‘Not
TABLE S Daily milk intakes of all black white children (mean ± I SD) Black 6 7
570
±
8
612
±
cant
9
“Degree (P
lactose intolerance in young children”2
Cutberlo
Nevin
Garza,’
M.D.,
and
ABSTRACT
The
test was compared white
children.
old, to
and
72%
240
ml
frequency young
prevalence
lactose No
and
children
than
the
ingestion
black
of 2 g lactose/kg
recommend 192
that
the
term
The American
as revealed
by the standard
lactose Journal
Am.
.
intolerance Nutrition
The
50 g)was J. Clin.
limiting
nor between blood
lactose
unreliable
no child
did
milk
tolerance
intakes
response an
29: 192’- 196,
was
intolerant
suggest milk
milk
children
as
not
existing the
black
glucose
Nuir.
milk
between
8- to 9-year-old
did.
yet
of
for
found
children,
(maximum
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
amounts
be a reason were
However,
children
of Clinical
to be lactose-intolerant,
greater
differences
to lactose.
.
to might
The accumulation of evidence that there is an age-dependent increase in the prevalence of intolerance to a large test dose of lactose in many of the world’s populations (1 -4) has raised doubts about encouraging milk consumption by such individuals. The traditional reliance on milk in supplementary feeding programs for children makes the issue important. In 1972 an international group (5) concluded that it would be highly inappropriate. . . to discourage programs to improve milk supplies...” on the basis of evidence then available. A similar statement was issued by the Food and Nutrition Board (6) and the American Academy of Pediatrics, Committee on Nutrition (7). However, these groups and others (8-10) have also emphasized the need for further investigation into the relationship between milk intolerance and lactose intolerance on the basis of the widespread occurrence of lactose intolerance. The controversy in the United States has centered on the provision of milk to black, Spanish-American, and other children with a high frequency of lactose intolerance. It has been characterized by unwarranted extrapolations and inconsistent terminology. Often the terms lactose intolerance, lactase deficiency, lactose malabsorption, and milk intolerance have been used interchangeably. We “.
found
lactose-intolerant white
response
were
intolerance
in Boston.
8- to 9-year-old
symptomatic
M.D.
intolerance
responses
significant
black milk
old
Symptom
lactose-tolerant and white
of lactose
8 to 9 years
milk.
of primary children.
Ph.D.,
with the occurrence of intolerance to graded amounts of milk in 69 black and 30 Of the black children studied, 11% of those 4 to 5 years old, 50% of those 6 to 7 years
of those
of
S. Scrimshaw,’
to
that
the
programs
intakes
of
for black
of 6- and 7-year-old
drank
significantly
less
at 0, 20, and 45 mm indicator
of
an
after
individual’s
1976.
be applied only when gastrointestinal symptoms, such as flatulence, bloating, abdominal cramps, or loose stools occur in response to the ingestion of a test dose of lactose (2 g/kg body weight), up to a maximum of 50 g. This sometimes occurs in the presence of blood glucose responses of >20 mg/lOO ml to a standard lactose tolerance test dose. Furthermore, distinctions should be made among the types of lactose intolerance. The intolerance may be caused by 1) congenital absence of lactase, a rare condition; 2) an apparently normal developmental decrease in the level of lactase-primary lactose intolerance-and 3) damage to the intestinal mucosa by any of a variety of agents-viral, bacterial, gluten, and the like-leading to secondary lactose intolerance. The term lactase deficiency should be applied only to secondary lactose intolerance, because primary lactose intolerance appears to be normal for other animal species and a majority
‘With
financial
Council. 2 Department
assistance
of
Nutrition
from
and
The
Food
National
Science
Dairy
Publi-
cation
2688. Predoctoral Fellow, Department of Nutrition and Food Science, Massachusetts Institute of Technology. Professor of Human Nutrition and Head, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
29:
FEBRUARY
1976,
pp.192-196.
Printed
in U.S.A.
RELATIONSHIP
OF
LACTOSE
INTOLERANCE
of humans. The term lactose malabsorption should be reserved only for cases where there is a “flat glucose response curve” after a test dose of lactose, with or without symptoms. Moreover, intolerance to small or moderate amounts of milk cannot be predicted from the results of a standard lactose tolerance test because of the large amount of lactose used and the unphysiological manner of its administration (I 1-13). This study in young children compares the prevalence of intolerance to 240, 360, and 480 ml of whole milk, or to the equivalent levels of lactose provided in a lactose-peanut butter mixture (PBL), with the prevalence of primary lactose intolerance revealed by the standard lactose tolerance test. Usual milk intakes and home attitudes toward milk consumption were also investigated. Parents were interviewed for their children’s medical and dietary histories, and their written consent was obtained. Subjects
and
methods
The subjects were 99 healthy age; 69 were black and 30 were Phase
children, white.
4 to 9 years
of
TO
MILK
193
INTOLERANCE
except that the lactose was provided in 240, 360, and 480 ml of whole milk consumed on 3 different days.
Results The percentages of children with positive symptom responses to graded doses of lactose when provided in the PBL mixture are given in Table 1 and the responses to lactose in the various amounts of whole milk are given in Table 2. Based on the respective sample sizes, the probabilities of having failed to find a child intolerant to 240 ml of whole milk range from 0.87 for a hypothetical prevalence of 1%, to 0.10 for a prevalence of 15% for black children 4 to 5 years of age. For black children age 6 to 7, the probability rate was 0.84 to 0.06 for hypothetical prevalences of I and 15%, respectively, and for black children age 8 to 9 the range was 0.81 to 0.10 for hypothetical rates of 1 to 10%, respectively. Milk intolerance was not observed at any level of intake in the white children. Table 3 gives the age-related prevalence of lactose intolerance. Children included in this table had symptoms of intolerance to either the standard dose of lactose given in a water solution or to lesser amounts when provided
I
Thirty children (20 black, 10 white) were provided with 12, 18, and 24 g of lactose in a peanut butter-jelly sandwich on 3 consecutive days. The mixture had a fat to lactose ratio similar to that of whole milk. The children were watched for at least 5 hr after the ingestion of lactose, and their parents were interviewed to learn whether any child developed symptoms while at home for
TABLE Symptom of lactose
the remainder of a 24-hr period. Children developing gastrointestinal symptoms, such as flatulence, bloating, abdominal cramps, or loose stools were not fed the next higher level of lactose unless the symptoms were equivocal, i.e., very mild and difficult to evaluate. In this case either the level was repeated or the next higher was tried. If more marked symptoms were noted at the next higher level, or if the symptoms remained about the same, the child was classified as intolerant to the lower level. When symptoms of intolerance were not observed or reported at the three lower levels, a standard lactose tolerance test was performed in most cases. Two grams of lactose/kg body weight (maximum 50 g) were provided in a 20% water solution to the fasting child. Microcapillary blood
Blacks 6-7 8-9 Whites 67 8-9
samples were obtained from the child’s fingertip at 0, 20, and 45 mm after the oral administration of the lactose solution. Blood glucose was measured using the glucose oxidase method. Again, children were observed for at least 4 hr after the lactose administration.
Age (yr)
I response in peanut
to graded butter
amounts
N
% intolerant tol8g
tol2g
to24g
10 10
0 10
10 30
40 40
7 3
0 0
0 0
0 0
TABLE 2 Symptom response to graded amounts of lactose found in whole milk Age (yr) Blacks 4-5 67 8-9
% intolerant
No. to 12g
to 18g
to24g
13 16 20
0 0 0
0 6 IS
8 12 20
2 9 9
0 0 0
0 0 0
0 0 0
Whites
Phase
2
Sixty-nine this phase.
children (49 black, 20 white) participated The design was similar to that of phase
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
in 1
4-5 67 8-9
GARZA
194 TABLE 3 Age-specific prevalence in children 4 to 9 years Age
Blacks 45 67 89 Whites 45 67 89
of lactose old
AND
intolerance
95
conlidence interval
No.
% intolerant
9 24 29
II 50 72
0046 2771 Sl86
2 14 10
0 0 20
023 257
in either whole milk or the PBL mixture. The lactose-intolerant group includes nine children with positive symptom responses to the PBL mixture or milk and who had no lactose tolerance test because consent could not be obtained, and five children with a blood glucose increase > 20 mg/ 100 ml and marked symptoms after the standard lactose tolerance test dose, but whose blood glucose increase was significantly lower (P < 0.025) than in children with no symptoms. Twenty-one percent of the lactose-intolerant children had positive symptom responses to 18 g oflactose in either whole milk or PBL, and approximately 40% had symptom responses to 24 g of lactose in either whole milk or PBL. Among the 69 black children studied, one 9-year-old child did report symptoms of intolerance at the l2-g level (provided in the PBL mixture). The mother stated that the child complained at home of mild abdominal discomfort. Both the child and the mother were unaware of any adverse response to milk. The next higher level of lactose was tried. Again, no symptoms were observed directly, but the child complained of mild abdominal discomfort at home. Both complaints occurred about 10 hr after the ingestion of lactose. Data were also obtained on the reliability of using blood glucose levels at 0, 20, and 45 mm after the ingestion of a standard test dose of lactose for predicting lactose intolerance. Eighty-two children were given a lactose tolerance test. Nine percent of the 55 with a maximum mg per 100 ml increase in blood glucose of more than 20 had symptoms, and 33% of the 27 having increases of less than 20 mg/lOO ml had no symptoms. Both false positive and false negative rates appear sub-
Downloaded from https://academic.oup.com/ajcn/article-abstract/29/2/192/4649249 by St Bartholomew's & the Royal London School of Medicine and Denistry user on 27 March 2018
SCRIMSHAW
stantial. However, it must be noted that nine children with symptoms at the lower level of lactose were not given a lactose tolerance test. Had they been tested, the percentage of children with an increase of less than 20 mg/l00 ml and no symptoms would probably have been lower. No differences in milk intake were found between either 6- to 7-year-old or 8- to 9-year-old black lactose-tolerant and lactoseintolerant children. No differences were found between the milk intakes of 6- to 7-year-old black and white children. However, differences between 8- to 9-year-old black and white children were found. When comparisons were made between mothers of lactosetolerant and lactose-intolerant black children, between mothers of lactose-tolerant black children and whites, and between black and white mothers of lactose-tolerant or -intolerant children, none of the apparent differences in milk intake were significant by the x2 test (a 0.05). Similar comparisons between fathers demonstrated no statistically significant differences. The milk intakes of the children and their parents are found in Tables 4, 5, and 6. =
Discussion The controversy children who have lactose-intolerant
over providing milk to a high probability of being rests on the potential of
TABLE 4 Daily milk intake of lactose-tolerant and -intolerant black children A ge
Lactosetolerant
yr
Lactoseintolerant (ml)
(ml)
6-7 8-9
585 570
a Degree
± ±
276 237
of freedom.
555 627
± ±
‘Not
TABLE S Daily milk intakes of all black white children (mean ± I SD) Black 6 7
570
±
8
612
±
cant
9
“Degree (P
