B-Vitamin status and intake in European adolescents. A review of the literature

Estado vitamínico e ingesta de vitaminas en adolescentes europeos. Revisión bibliográfica

J. Al-Tahan¹, M. González-Gross^1,2 and K. Pietrzik¹

¹Institut für Ernährungs- und Lebensmittelwissenschaften. Fachgebiet Humanernährung. Rheinische Friedrich-Wilhelms Universität. Germany.
²Facultad de Ciencias de la Actividad Física y del Deporte. Universidad Politécnica de Madrid. Spain.

ABSTRACT

Background: National and international recommendations for the intake of B vitamins in adolescents consist of estimates and extrapolations from adult values. Due to increasing growth and therefore relatively high energy and nutrient requirements adolescents are a vulnerable group from the nutritional point of view. In addition, a deficient intake of several B vitamins is strongly connected with the development of cancer, neural tube defects and cardiovascular diseases.
Objective: The aim of this work is to assess dietary intake and status of B vitamins and homocysteine of European adolescents on the basis of published data.
Methods: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like “vitamin B”, “homocysteine”, “Europe”, etc. Studies published between June 1980 and December 2004 were analysed for this review. Results of the intake of B vitamins were compared with the EAR or AI, respectively, as recommended by the U.S. Institute of Medicine. Due to lacking reference values for adolescents results of blood status as well as homocysteine were compared to different thresholds for adults.
Results: Considering the limitations of the comparability between the reviewed studies e.g. by different methodologies, sample size, age groups, the average intake of B vitamins surpassed the EAR and AI. Boys were better supplied with B vitamins than girls. The intake decreased with increasing age in both genders. A possible deficiency of folate was noticed and girls in particular seemed to be more at risk. Clear regional tendencies for the vitamin intake could not be observed. Results of vitamin B₆, B₁₂, folate in blood, and homocysteine were levelled in-between the thresholds. Though the great standard deviation of folate increased the probability of a deficient supply in parts of the population.
Conclusions: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance.

Key words: B-Vitamins. Homocysteine. Adolescents. Europe. Review

RESUMEN

Palabras clave: Vitamina B. Homocisteina. Adolescentes. Europa. Revisión.

Introduction

Adolescence is characterized by relatively high energy and nutrient requirements compared to remaining life stages on the one hand and a peculiar lifestyle and dietary habits on the other hand. Due to increasing growth, change of body composition and lack of interest in nutrition adolescents are a vulnerable group from the nutritional point of view. Irregular meals, high consumption of products rich in sugar and fat may lead to nutritional deficits^1,2. According to Rolland-Cachera et al.³, the possibility of good nutrition is continuously improving in Western European countries whereas the nutritional intake and quality is decreasing, propitiating the prevalence of nutrition-related diseases. During adolescence eating habits and lifestyle factors are mostly established. Increasing evidence demonstrates that the risk factors for the most prevalent chronic diseases start to implement at this early phase^4-6. Additionally, recent studies confirm former data referring to the connection between diet quality and cognitive development^{7, 8}, attention, intellectual⁹ and physical¹⁰ performance.

Furthermore, the comparability of available data on dietary intakes and nutritional status in populations of adolescents in Europe bears plenty of difficulties as recently stated by Lambert et al.¹⁶. This is mainly due to the lack of consensus on methodological approaches used. In their systematic review of surveys of dietary intake and status in children and adolescents conducted in Europe, Lambert et al.⁸ analyzed seventy-nine surveys from 23 countries. From them, data on energy, protein, fats, carbohydrates, alcohol, vitamins, minerals and trace elements were collected and tabulated. Data on energy, protein, total fat and carbohydrate were given in a large number of surveys, but information was very limited for some micronutrients. The aim of the present review is to complement the review done by Lambert et al. with a more in-depth analysis of vitamin B status of European adolescents. Therefore, we have searched for additional studies not included in their review. Furthermore, reviewed studies do not include all B vitamins, but especially focus on thiamin, riboflavin, pyridoxin, cobalamin and folic acid status. Biotin, niacin and pantothenates are analyzed less frequently. Homocysteine (tHcy), a product of methionin metabolism, is strongly connected with folic acid, cobalamin and pyridoxin status and is regarded to be a good indicator for vitamin status (vitamin B₆, B₁₂, and folate). So far, there exist no reference values for tHcy status in children and adolescents. As an independent risk factor for cardiovascular diseases tHcy is also dealt with in this paper.

Material and Methods

Studies evaluating the intake of B vitamins and blood values of B vitamins and tHcy in adolescents of European countries were included in this review. Adolescence is defined as a period of young persons in the process of evolving from a child into an adult, i.e. roughly between the ages of thirteen and seventeen¹⁷. However, cut-off points vary in different articles so that data from younger and older persons had to be included. Due to the scarcity of available data all surveys that had been found were used. The database Medline (www.ncvi.nlm.nih.gov) was searched for studies published between June 1980 and December 2004. Terms like “adolescents”, “vitamin B”, “homocysteine”, “European”, names of European countries and technical terms of the different B vitamins were entered as well as combinations out of these terms. In addition, references of relevant articles were viewed for further information.

Intake data of B vitamins have been compared to the Estimated Average Requirements (EAR) and the Adequate Intakes (AI) established by the Institute of Medicine¹⁸ (table I). As stated by the US Institute of Medicine, EAR and Recommended Dietary Allowances (RDA) for thiamin, riboflavin, vitamin B₆, folates and vitamin B₁₂ were extrapolated from adult values. For biotin and pantothenates, as data were too sparse to set an EAR, an AI was developed. The method is explained elsewhere¹⁸. The EAR is the value within the Dietary Reference Intakes recommended to be used in order to estimate the prevalence of inadequate nutrient intake of a life stage or gender group¹⁹. For those nutrients without an EAR, the AI should be used for analysis.

Lacking reference values for adolescents obliged us to compare blood values with thresholds for adults in order to assess vitamin deficiency (table II). Different blood reference values had been investigated by Schrijver²⁰. The reference value for the biomarker methylmalonic acid (MMA) is adapted from Klee and Thomas^{21, 22}. Elevated MMA values (> 0.4 μmol/L) may indicate a deficiency of vitamin B₁₂ for adults. According to Bässler et al.¹² tHcy > 10 μmol/L correlates with a higher risk for cardiovascular diseases. The upper borderline of tHcy is 10-17 μmol/L in accordance with Kasper [23].

With the method explained above 83 studies were found including 14 review articles. Sixty-nine articles gave detailed information which is shown in the tables III-VII. Thirty-six studies of these 68 articles were cross-sectionally designed, 15 were case-control studies, eight were cohort studies and nine were review articles. Five studies were found comprising a sample size of less than 50 persons. There were nine studies between 50-100, 22 studies between 100 and 500, 11 studies between 500 and 1000 and 11 with more than 1000 participants. One study did not state the sample size.

Looking at the countries where the studies were carried through, 11 of them took place in the United Kingdom (UK), eight in Spain (ESP) and Germany (GER) each, five in Poland (POL), four in the Netherlands (NL) and Norway (NW) each, three in Sweden (SW), Austria (A), Italy (IT), Greece (GR), France (F) and in the Czech Republic (CZ) each, one in Belgium (B), Switzerland (CH), Denmark (DEN), Estonia (EST) and in the Slovak Republic (SLOVAK) each.

In an attempt to illustrate and to compare reviewed data, Figure 1 depicts the mean B vitamin intakes of adolescents in several European countries. Of all data available from one country, the average intake was calculated by adding primarily the arithmetic means and dividing by the number of studies conducted in one country. When not applicable weighed and geometric mean, and median were included in this calculation instead of the arithmetic mean. Results are shown in a falling order from the country with the highest to the country with the lowest intakes. Clear geographical tendencies can not be seen. Intakes of vitamin B₁₂ and folates are higher in Southern Europe (Spain, Portugal, France) and Denmark and lower in the United Kingdom. Remarkable is that Nordic countries as Sweden, Denmark, Norway and Eastern Europe (Slovakia and Estonia) are represented with highest intakes especially for riboflavin and niacin intakes. Portugal, Czech Republic, Denmark and Germany have the lowest intakes for these vitamins. The distribution of the remaining vitamins is too inconsistent to give evidence. All in all, these data have to be taken with caution as they come from different studies which used different methodologies. These data may be not representative for a country.

In the reviewed studies, the focus was set on either biochemical methods (33 studies) or assessment of dietary intake (27 studies). The applied methods subdivide into prospective methods as seven-day weighed dietary records (7 studies), seven-day weighed dietary records with duplicate diets (one study), three-day dietary records (5 studies), four-day estimated food diary (one study) and retrospective methods such as diet history (5 studies), seven-day diet history (one study), 24- hour recall (10 studies), 48-hour recall (one study), food frequency questionnaire (12 studies), not further explained questionnaire (3 studies) and interview (2 studies). The biochemical methods divide into blood samples (32 studies) and 24-hour urine (one study). A combination of biochemical and dietary intake methods was applied in 11 studies. However, studies working at dietary intake often used combined methods e.g. 24-hour recall and food frequency questionnaire.

Those who compared their results of dietary intake with any reference data preferred national recommendations. Only in one review article²⁴ the EAR were chosen as reference values for the population.

All studies analyzed data of both genders except for Van Poppel et al.²⁵, Cruz¹ and Kafatos et al.²⁶. The study carried out by Van Poppel et al.²⁵ was performed only on males as part of the Dutch Nutrition Surveillance System. Cardiovascular risk factors, hematological, iron and vitamin status as well as food consumption by means of 24-hour recall were assessed in 126 boys. Kafatos et al.²⁶ investigated three composite Cretan diets of which one diet is representative of 12-year old boys by means of a seven-day weighed dietary record, chemical analyzes and the Greek food database.

Dietary intake of B vitamins

Supplementation and fortified food

The minority of the analysed studies aimed to detect the use of vitamin supplements. In Norway, Bjorke Monsen et al.²⁹ identified 17% of the total study population as daily users of vitamin supplements that contained cobalamin and/ or folate. Fifty-six percent of the supplements used contained both vitamins, and this percentage was equally distributed among the age groups 1-10, 10-15 and 15-19 years. In contrast, in Belgium De Laet et al.³⁰ mentioned that 2.6% of the 10-14-year-old and 4.6% of the 15-19-year-old sample regularly took vitamin supplements containing folate, vitamin B₆ or vitamin B₁₂. Serum concentrations of folate and vitamin B₁₂ were comparable with children not taking any supplements. In a case-control study dealing with dietary intake of young vegans and omnivores in Sweden³¹, omnivores used dietary supplements less frequently than vegans (43% compared with 87%). Sex differences could not be observed.

In Germany, Sichert-Hellert et al.³² found a significant rise in intakes of fortified nutrients with time. Between 1987-1995, the intake of vitamin B₁, B₂, B₆ and niacin from fortified food rose from 8-19% to 20-32%. In contrast, folate intake from fortified food increased more slightly from 19% to 29%.

High cereal eaters comprise a special subgroup of adolescents. Due to the fortified breakfast cereals they have a higher intake of B vitamins. Cereals provide 5% of total energy for girls, but 18% of folate, thiamin and riboflavin, 15% of B₆ and 13% of niacin³³. Articles working on Ready-To-Eat-Cereals (RTEC) show similar results^{34, 35}.

B-Vitamin status

Table VI depicts all studies dealing with B vitamin status. Detailed information mainly is given on serum folate, serum vitamin B₆ and B₁₂. Other parameters like red blood cell (RBC) folate, methyl-malonic acid (MMA), pyridoxalphosphate (PLP) and pyridoxic acid (PA) are mentioned in some studies. No sex differences were observed except for Marktl et al.³⁶ in Viennese children. In their study, boys were better supplied with thiamine and riboflavin than girls, but not with pyridoxine. The authors also pointed out the correlation of vitamin status and socio-economic level. Generally, a negative correlation between folate, B₁₂ and age can be seen. Bjorke Monsen et al.²⁹ described a maximum concentration of serum cobalamin at years ~3-7. Afterwards, there is a gradual decrease towards the concentration observed in adults. RBC folate showed a stable median concentration of ~220 nmol/L.

Table VII shows several studies dealing with tHcy. The majority of the revised studies report an agedependant tHcy status. De Laet et al. and Tonstad et al.^{30, 37} called the results in younger subjects as ~50% of the values detected in adults. Some authors additionally observed inverse relationships between tHcy and blood indices of folate and vitamin B₁₂ ^{29, 38, 39}. Bates et al.⁴⁰ also found negative correlations with tHcy and vitamin B₆ as well as seasonal variations of tHcy with an unexpected minimum of tHcy in winter.

Gender differences are reported by some authors but not by all^{29, 41}. Some of the revised studies revealed significantly higher tHcy concentrations in boys than in girls. Sex differences enhanced during and after puberty ⁴². Kosch et al.⁴³ spoke of a tendency towards two age dependant peaks during infancy and during puberty (9,0 μmol/L).

tHcy positively correlated with sugar intake in one study³⁷. Additionally, tHcy concentrations were elevated in obese adolescents taking part in a weight-reduction program. The determining factor was the lean body mass⁴⁴. A link between tHcy and creatinine was mentioned in four studies^{37, 39, 45, 46}.

Few studies work at the influence of methyl-tetrahydrofolate-reductase (MTHFR) genotype on tHcy concentration. Raslova et al.⁴⁷, Gallistl et al.³⁹ and Kosch et al.⁴³ analyzed the 677 C → T MTHFR mutation. However, none of the authors found an association between tHcy and the 677 C →T MTHFR mutation. In contrast, Mainou Cid et al.³⁸ revealed a higher tHcy concentration in 80% of the children (of parents with cardiovascular diseases (CVD)) with the T/T genotype. Suboptimal B vitamin levels were also associated.

Discussion

Before comparing and assessing the viewed results, several difficulties should be mentioned. Generally, in order to get an idea of a population’s nutrient supply further statistical tools e. g. mean, standard deviation, median and percentiles are needed. The majority of the revised studies only published mean and standard deviation. Additionally, as EARs are developed by medians, the correct assessment of the dietary results is only possible by using the median. Furthermore, it is important to consider the distribution of the nutrient supply. If the population’s nutrient supply is normally distributed median ± 2SD describes the normal intake values of a healthy and well-nourished group. The 2.5^th percentile (EAR -2SD) represents the minimal requirement of a specific nutrient. Therefore, the dimensions of undernourishment are shown by the 2.5^th percentile. The median of a population’s intake might be higher than the EAR despite a larger group of individuals whose intake is below the 2.5^th percentile. In this paper, means have been used to compare results instead of medians due to the lacking information.

For a comparable study it is also necessary to have both identical methods of measurement and identical cut-off points. Furthermore, age groups should cope with those of recommended intakes (9-13 and 14-18 years). Observing the published results, chosen age ranges are quite random and make comparison even more difficult. Another problem, already recognized by many authors, are the food composition databases. For example, Kersting et al.⁴⁸ evaluated the vitamin intake of 1- to 18-year-old children participating in the DONALD-Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study) with the food database LEBTAB. Other countries used different food databases e.g. the food data bank of the Swedish Food Administration²⁷, the French food composition Table 5 or McCance & Widdowson´s food tables⁴⁹. Different food databases reduce the comparability between European countries. Even within a country there are sometimes different food databases that make comparability even worse⁵⁰. Subsequently, standardized food databases are also needed. However, modified parts that reflect a country’s dietary custom could be useful. As objectives vary between the distinct scientific groups different priorities are set up and eventually different methods of measurement are used. A European multicenter-study like the recently started HELENAStudy (Healthy Lifestyle in Europe by Nutrition in Adolescence) including homogeneous objectives, one central planning and standardized implementation may solve this problem in many aspects¹⁵.

The combination of biochemical methods and dietary intake assessment leads to more accurate data about the nutritional status of human beings. However, the selection of methods depends on the vitamin and on the practicability. In the case of folate the ideal method would be a combination of intake data, RBC folate, plasma folate and tHcy concentration²⁴. Folate intake data on its own are skewed due to the immense variability (30-90%) in losses during preparation. As a water soluble and heat sensible vitamin folate can be easily washed out and destroyed by cooking^{12, 51}. Bates et al.⁵² explained that on the basis of plasma PLP levels, very few of the young people had poor vitamin B₆ status: only 0.5% on the basis of a 20 nmol/L cut-off or 6% on the basis of a 30 nmol/L cut-off. In contrast, around 54% had a poor status on the basis of a cut-off of 1.80 for erythrocyte aspartate aminotransferase activation coefficient (EAATAC). However, the authors admitted that the latter indicator could be very methoddependent and may not be appropriate for their study. The commonly used parameter serum B₁₂ is imprecise for the assessment of vitamin B₁₂. 50% of the elderly population show biochemical alterations (holo TC, MMA) despite of serum B₁₂ values in normal ranges. More accurate but also more expensive are the parameters that test the metabolic active part of holo-transcobalamin and methylmalonic acid^53-55.

Results of serum vitamin B₁₂, serum total vitamin B₆ and PLP all exceed the threshold for adults. Only one study investigated MMA²⁹. Results (0.17 and 0.14 μmol/L) are lower than 0.4 μmol/L indicating that there is no sign for an impaired vitamin B₁₂ status. Apart from two studies^{29, 60} results of serum folate exceed the reference values for blood. This is not contradictory to the results of folate intake. Despite a suboptimal nutrient intake normal biochemical parameters like serum folate are feasible. Regarding the standard deviations and lower ranges, 44% of these values are in-between the reference values or below. There is only one study that incorporated RBC folate⁶¹. Results (597 nmol/L ± 241) are close to the upper threshold value (500-600 nmol/L). However, the great standard deviation leads to the conclusion that a few of the 15-20- year-old definitely have a suboptimal supply. Adolescents’tHcy values do not exceed the reference range for adults (10-17 μmol/L). As shown in previously published studies^30,37 tHcy for adolescents corresponds to ~50% of values detected in adults and increases with age.

It is important to bear in mind that adolescents are not small grown-ups. This group has its own specific needs. Adolescents clearly have higher nutrient requirements than other life-stages due to the rapid growth and metabolic changes. Therefore the assessment with adult values lacks of comparability. Possibly adolescents also have higher normal blood values. Thus, further investigations are necessary in order to set new reference values for adolescents.

Conclusion

Mean dietary intake of B vitamins except for folate mostly exceed Estimated Average Requirements and Adequate Intakes in both, age groups and genders. Boys are better supplied than girls and the intake of B vitamins falls with increasing age. Inadequate intake can be seen only for folate and again girls are more at risk for folate deficiency. Clear geographical tendencies do not exist. Results for B vitamins in blood mostly exceed thresholds. However, blood samples might be unrepresentative for the population and the assessment with adult thresholds lacks of comparability.

In order to evaluate these intake data correctly, percentiles, means and standard deviations should be indicated in nutrition surveys which are missing in the reviewed literature. Representative blood samples are lacking for most age groups. Further, more accurate methods should be chosen instead of cheaper alternatives. Before giving any recommendations for B vitamin supplementation the real vitamin B status of European adolescents should be established.

A prerequisite to make intake data more accurate is the adaptation of food databases to the local food habits including fortified food. The same methods as well as the same reference values should be utilized for a better comparison between European studies. Estimated Average Requirements should be assessed in order to analyze a group’s dietary intake. Reference values for B vitamins and tHcy in blood specimens for European adolescents still must be established. There is a strong need for further investigations.

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Correspondence:
Dr. Marcela González-Gross
Facultad de CC. de la Actividad Física y del Deporte
Universidad Politécnica de Madrid
c/ Martín Fierro, s/n
E-28040 Madrid
E-mail: marcela.gonzalez.gross@upm.es

Recibido: 12-III-2006.
Aceptado: 15-V-2006. ]]> 1 2000 54 ^s1 ^s1 1 S29-35 2 1999 2 3 2000 54 ^s1 ^s1 1 S41-46 4 1994 48 736-748 5 2000 70 139-147 6 2004 92 ^s2 ^s2 2 S67-73 7 2004 160 767-792 8 2004 161 2005-2013 9 1993 43 6-11 10 2004 20 632-644 11 1999 129 779-782 12 2003 3 13 2002 72 46-52 14 2004 92 ^s2 ^s2 2 S213-S222 15 2005 29 ^s2 ^s2 2 S66-S77 16 2004 92 ^s2 ^s2 2 S147-211 17 1995 5 18 1998 19 2000 20 1991 21 2000 46 1277-1283 22 2000 23 2004 24 2002 72 351-359 25 1991 66 161-169 26 2000 100 1487-1493 27 1993 82 472-480 28 1980 128 415-421 29 2003 30 1999 69 968-972 31 2002 76 100-106 32 2000 54 81-86 33 2003 6 815-820 34 1999 18 171-178 35 2001 4 101-107 36 1982 52 198-206 37 1996 40 47-52 38 2002 56 402-408 39 2000 23 1348-1352 40 2002 87 71-79 41 2001 24 969-971 42 2003 41 1418-1426 43 2004 91 308-314 44 2001 50 1220-1223 45 2001 20 409-418 46 2001 7 1242-1249 47 2000 49 651-658 48 2000 70 48-53 49 2001 52 109-116 50 2005 21 1 1 51 DACH 2001 1 52 1999 2 529-535 53 2004 50 1043-1049 54 1985 18 261-266 55 2003 49 455-462 56 1994 71 897-918 57 2003 57 ^s1 ^s1 1 S35-39 58 1996 75 474-481 59 2002 15 429-438 60 2003 20 867-868 61 2000 137 386-392 62 2000 72 1392S-1398S 63 1990 64 13-22 64 1991 50 37-43 65 1997 51 87-91 66 1997 41 150-154 67 1995 49 555-564 68 1996 ^s415 ^s415 415 1-19 69 1998 42 13-16 70 2001 71 325-31 71 2001 4 1433-8 72 1992 17-25 73 1995 174-183 74 2001 4 1325-9 75 2001 86:529-34 76 1997 56 303A 77 2000 72 762-9 78 1996 41 18-22 79 1992 297-300 80 2000 45 10-15 81 1999 69 664-71 82 2002 15 857-64 83 2000 23 84-7 84 1999 99 2070-2 85 1998 44 662-4 86 2003 167 275-86 87 2001 40 149-54 88 2000 38 675-6