Lactase non-persistent genotype influences milk consumption and gastrointestinal symptoms in Northern Russians

Milk is an important source of everyday nutrition. Bovine milk is a rich resource of nutrients containing lipids, proteins, amino acids, vitamins and minerals. Such substances as immunoglobulins, hormones, growth factors, cytokines, nucleotides, peptides, polyamines, enzymes and other bioactive peptides are also present in milk [1, 2]. Milk has been considered a major source of calcium as well as the simplest and most "cost-effective" way to ingest calcium [3, 4]. In that dairy products also provide other important nutrients, their consumption improves the nutritional quality of the diet appreciably [4, 5].

This notwithstanding, the consumption of milk has decreased over the last decade in Northern Europe [1, 5]. Data on milk consumption in Russia in recent years have been very limited and available only from market analyses, which show a decrease in milk consumption in some regions of country [6]. Consumption is low among young Northern Russians [7]. The above-mentioned properties of milk make it important for everyday nutrition, especially for children. Recently a national program, "School milk", aimed to supply schoolchildren with the essential amount of milk daily, has been implemented in Russia [8].

Adult-type hypolactasia, characterized by the down-regulation of lactase enzyme activity in the intestine during human growth, is inherited as an autosomal recessive trait [9, 10]. The first genetic variant associated with adult-type hypolactasia, a one-base polymorphism C > T -13910 (rs 4988234) upstream of the lactase encoding gene on chromosome 2, was identified in 2002[11]. This -13910 C/T is the most common variant of lactase persistence among Caucasians [12]. Several other population-specific variants nearby have been identified, some of them only suggestive [13‐16]. The -13910C/T has been shown to be located in the OCT-1 binding site and acts as an enhancer. Nowadays the genotyping can be used as the test for adult-type hypolactasia with 100% specificity in cases of unspecific abdominal complaints [17, 18].

Milk contains disaccharide lactose, which may cause gastrointestinal problems in adults by reason of its poor digestion in part of population. In Northern Europe lactase persistence is common, which allows the majority of the population to drink milk without any consequences [19]. However, in populations where the frequency of the lactase persistent genotype is rather low the consumption of milk may cause complaints in the digestive tract [20]. The development of symptoms depends on the amount of milk consumed as well as on individual sensitivity. It has been shown that subjects with hypolactasia can tolerate moderate quantities of milk, up to 12 g of lactose/200 ml of milk. If the daily dose of lactose is consumed in small portions and also with a meal, the likelihood of symptoms is low [20‐22].

The most common gastrointestinal (GI) symptoms which characterize intolerance to lactose are flatulence, diarrhea, gurgling, abdominal distension and abdominal cramping [22‐24]. The appearance of symptoms is clearly explained by mechanism of lactose utilization. Lactase-phlorizin hydrolase splits the entering lactose into two monosaccharides, glucose and galactose. The lack of lactase activity leads to intake of indigested lactose into the bowel. The osmotic effect causes diarrhea [25], while an increased level of fermentation in the intestine leads to increasing production of gases and thus to flatulence [26, 27].

The prevalence of adult-type hypolactasia (lactase non-persistence, -13910C/C) among Northern Russians has been found to be 35% [7]. It has also been shown that the prevalence of the -13910C/C genotype among Russians living in the central part of the country ranges from 36 to 50% [28, 29]. This frequency is twice as high as in Finland and many times higher compared with other Scandinavian countries [30‐33]. It also exceeds the prevalence of the -13910C/C genotype among Estonians [34].

Recent studies have shown that subjects with intolerance to lactose tend to reduce their consumption of milk, which is predictable as far as they suffer from symptoms after milk consumption [31, 35‐38]. In our previous study [7] subjects showed no differences between genotypes in the frequency of GI complaints during life. We found, however, that the consumption of milk is extremely low among the Northern Russian population compared with other Northern populations. Does milk consumption influence the appearance of GI symptoms in a population with a high frequency of the lactase non-persistent genotype but with very low consumption of milk on the whole?

In the present study we sought to test two hypotheses: 1) subjects with lactase non-persistent genotype (-13910C/C) possibly have more gastrointestinal symptoms associated with milk 2) subjects with lactase non-persistence avoid using milk.

The prevalence of the -13910C/C genotype (lactase non-persistence, LNP) among 518 young students from North-West Russia was found to be 35% (n = 180) while the -13910C/T genotype was found in 46% and -13910T/T in 19% of participants.

About sixty percent of all subjects reported GI symptoms (Table 1). The most frequent symptom was stomach-ache. However, no statistically significant differences were revealed in the frequency of gastrointestinal symptoms in total between the LP and LNP genotype groups. The study brought out no statistically significant differences in symptom appearance between male and female participants.

The majority of subjects consumed very small amounts of milk daily. Only about 40% of all participants used milk every day. Almost 50% did not use milk at all and 13% reported consumption of milk more seldom than daily (Table 2). Among carriers of the LNP genotype there were 10 percentage units fewer milk-consumers in comparison with the LP group (32.2 and 42.0%). The differences were statistically significant (p = 0.03). Sour milk consumption did not show significant differences in symptoms between LP and LNP subjects.

Milk consumption was associated with GI disorders in 13.3% of subjects with the LNP genotype and in 7.1% of subjects with the LP genotype (Table 3). Complaints of GI disorders caused by milk consumption were different between the genotypes (p = 0.02).

Among all types of food analyzed only milk resulted in statistically significant differences in symptoms between LP and LNP subjects (OR = 1.95, CI 1.03-3.69) (Table 4). In regression analysis there was no connection between consuming food and the appearance of symptoms except in milk consumption.

Young Northern Russians consume very small amounts of milk daily. However, among LNP genotype carriers there are even less milk-consumers than among LP subjects. Our findings demonstrate that milk is the only type of food having an influence upon the appearance of GI disorders differently by genotype. We may conclude that subjects with lactase non-persistence (-13910C/C) have more symptoms from milk. Subjects with lactase non-persistent genotype avoid using milk.

Sour milk consumption brought out no differences between the genotypes. This is in accord with the previous proved finding that sour milk is better tolerated than milk by persons with lactose intolerance [21, 39]. Sour milk contains less lactose as a result of bacterial fermentation.

All students recruited for this study were considered healthy. However, only forty per cent of them did not report any GI symptoms and half of them reported stomach-ache, which was the most frequent symptom among all subjects without links to genotype. Possibly this finding requires further investigation of student health to clarify the causes of the frequent GI disorders among a healthy young population.

Regarding other populations it was shown that only flatulence occurs significantly more frequently among LNP subjects [39, 40]. Jussila and associates [41] showed that loose stool was a more frequent symptom in subjects with selective lactose malabsorption.

The northern Russians use very small amount of milk daily. However LNP subjects use less milk than people with LP genotype. Such a self-prescribed reduction is in agreement with a study in Finnish children with the -13910C/C genotype, who naturally diminished their usage of milk [31] and also with a study in children of other ethnicities [42]. It was also shown that other age groups also tend to reduce their milk consumption because of the appearance of symptoms after milk [24, 38].

It is possible to assume that the low rate of symptoms was partly related to the low milk intake in our study population. It is likely even if the prevalence of adult type hypolactasia in the study population is as much as 35% and low milk consumption is reported symptoms appear less probably than in other populations. Another explanation for the low rate of symptoms may be the age of lactase activity down-regulation. Since there are no studies estimating the age of decline of enzymatic activity in Russians there is a slight possibility that this group was too young to demonstrate differences in GI disorders.

Vast majority of our randomly selected students were from North-West Russia [7]. Based on the farming history, this area was determined in Soviet Union as milk production area. The region has still been considered as one of the country's milk and meat production areas. The gene-culture co-evolution between cattle milk genes and humans lactose tolerance has been verified for North Central Europe [43] and it seems to be also in north-western part of Russia.

Since milk is an important source of nutrients there are numerous studies aimed to demonstrate the advantages and disadvantages to milk restriction or elimination from the diet. The lack of milk in nutrition in the young population is strongly associated with decreased bone mineral density and leads to osteoporosis in older age [42]. Precise statistic data of prevalence of osteoporosis among the Russian population are lacking. However, it is obvious that osteoporosis as well as a higher risk of bone fractures connected with it is an actual problem for Russia [44]. Building peak bone mass during childhood and adolescent can be the best means of preventing osteoporosis in older age.

It is surely warranted to increase milk consumption among the Russian population by providing a federal program. The benefits from an increase in milk consumption are obvious. At the same time our study has shown that lactase non-persistent subjects have higher frequency of GI disorders even in population with very small amount of milk consumed. It may be predicted that in the case of increasing milk consumption symptoms may appear more frequently and may increase the need for medical consultation and care. It is therefore important either for people themselves or for health care staff to be alert to lactase persistence/non-persistence.