Young females are at risk of nutrient deficiencies due to poor diets and higher requirements for micronutrients, such as iron and folate especially in the periconceptional period and during pregnancy [1
]. Some young women’s dietary patterns which include the avoidance of micronutrient-rich meat and poultry [2
], and social influences such as the desire to have a lower BMI despite having a BMI in the normal range [3
] resulting in chronic dieting, could further negatively impact their nutrient status and related health outcomes. Multiple micronutrient deficiencies is a worldwide problem, and extends to a range of population groups including young and apparently healthy women [4
]. Due to the significant role that vitamin and mineral statuses play in disease prevention, it is important to identify deficiencies in sub-populations. Data on the micronutrient status of women are less readily available and incomplete.
The adequate intake of vitamins and minerals such as iron, zinc, copper, selenium, vitamin B12
and folate is essential for optimal health [4
]. Iron deficiency (ID) and iron deficiency anaemia (IDA) are common worldwide especially among young women, and have been shown to decrease general health and wellbeing [5
]. IDA affects work and exercise performance, increases fatigue, and compromises immunity and neurological function [5
]. IDA has been linked to impaired cognitive function and poor pregnancy outcomes [7
] including low birth weight [8
Both iron and zinc are readily bioavailable from animal products [6
] and naturally coexist in foods, so marginal deficiencies of both minerals have been associated [6
]. Zinc, copper and selenium are involved in various aspects of metabolism [4
]. Zinc functions in pathways that are necessary for growth, immunity, reproductive function and neuro-behavioural development [9
]. Measurement of serum or plasma zinc concentration is currently the only biochemical indicator recommended for the assessment of the zinc status of populations [10
]. Copper is a component of many oxidative enzymes, and impacts on iron status, with both high and low copper status being associated with iron metabolism and anaemia [11
]. Assessment of copper status has challenges like that of other minerals, and serum copper is used widely as a biomarker of copper status. Selenium plays a key role as an antioxidant through its association with glutathione peroxidase, and has broader functions as a component of selenoproteins [12
]. Dietary intake resulting in suboptimal selenium status has been associated with increased risk of cancer, cardiovascular disease, thyroid disease, infertility and adverse reproductive outcomes [13
]. There are no recent reports of blood selenium concentrations among young women in Australia.
and folate are involved in single-carbon transfer and DNA synthesis [4
], and are particularly important for young women. Long-term, vitamin B12
deficiency impairs cognitive function and it is important in the prevention of neural tube defects (NTD) [4
]. Vitamin B12
is a cofactor in the metabolic transformation of homocysteine to methionine, a reaction that also requires folate [14
]. Vitamin B12
deficiency has been linked to megaloblastic and pernicious anaemia [4
] and a decline in cognitive function in older age [15
]. Serum vitamin B12
is a biomarker of vitamin B12
deficiency, and the metabolites, methylmalonic acid (MMA) and homocysteine are functional indicators [4
]. Elevated plasma total homocysteine (tHcy) has been shown to increase the rate of pre-eclampsia and is related to other poor pregnancy outcomes [16
]. Chronic folate deficiency can result in anaemia, and together with vitamin B12
deficiency has been associated with cognitive dysfunction, decline in physical function and osteoporosis in the elderly [17
]. Vitamin B12
is found only in animal products, and therefore predisposes vegetarians, a common dietary practice among young women, to a greater risk of deficiency [14
]. High dietary intakes or supplements of folate and vitamin B12
decrease elevated plasma tHcy concentrations [18
] and reduce the risk of NTD [19
Recognition of nutrient deficiencies in women of reproductive age is important not only because nutritional status affects women’s health and wellbeing, but also because deficiencies are associated with adverse pregnancy outcomes. Also, deficiencies in micronutrients such as folate, vitamin B12
, iron and trace elements can have adverse consequences on infant mortality and morbidity. There are limited biochemical data on the micronutrient status of young women in Australia. We have undertaken a cross-sectional study in which we collected dietary data, anthropometric parameters and behavioural characteristics of young female university students [2
]. The aims of the present study are to determine (i) the concentrations of selected micronutrients in women of childbearing age; (ii) the prevalence of deficiency; and (iii) the relationships between micronutrient biomarkers that may exist in this population.
The present study in a group of young women describes the nutritional status of selected micronutrients by using a range of biomarkers. Selection of an apparently healthy group allowed for the assessment of nutrient status and examination of relationships between micronutrients independently of any significant health confounders. The focus of the study was the determination of micronutrient status in young female university students of childbearing age since this group is at risk of deficiency because of the higher micronutrient requirements for maintenance of metabolic stores, and increased requirement potentially due to pregnancy and lactation. The results from the present study show a high prevalence of poor iron status with the most common abnormality being hypoferritinaemia. Other significant findings were the presence of low vitamin B12 status concurrent with a dominance of elevated E-folate concentrations.
Hypoferritinaemia and IDA were observed in 33.9% and 3% of participants, respectively. Sub-optimal vitamin B12 status, evidenced by low serum vitamin B12 and elevated MMA concentrations, were found in 11% and 5% of women, respectively. Optimal selenium concentrations were achieved by a third of participants. In contrast, the participants were not at risk of low folate status, as 99.7% had E-folate concentrations above the reference range.
Serum ferritin concentrations <30 μg/L indicate an increased risk of ID, particularly if iron bioavailability is decreased or iron demands are increased [28
]. In the present study, the median serum ferritin concentration (22.0 ± 1.5 μg/L) was similar to concentrations that are reported for other young women [29
] and represent a substantial increase in the risk of adverse functional effects. We found significant relationships between serum ferritin concentrations and all measured biomarkers of iron status, and we confirmed the previous finding that STfR is inversely correlated to transferrin saturation, Hb and serum iron concentration [32
The mean serum zinc concentration reported in the present study is consistent with other reports, including levels in young women of childbearing age [33
], a study in a general French adult population [34
], and concentrations were higher than those reported in omnivores and vegetarians [31
]. Factors that may decrease plasma zinc include vegetarian diets, where as much as 35% of a reduction in plasma zinc is reported [36
]. Despite the association between zinc and iron, only a weak negative correlation was seen between serum zinc concentrations and STfR but not with other biomarkers of iron status.
There is limited information on selenium and copper status in Australia. Serum copper concentrations in our study were similar to those observed in women who followed a lacto-vegetarian diet and to that observed in Italian adults [37
]. In contrast, our results were slightly lower than non-vegetarians [38
], and healthy female adults [39
]. In the present study serum copper concentrations below the reference range were observed in 22% of participants. Serum copper concentrations were positively related to sTfR and inversely related to serum ferritin concentrations, indicating an inverse relationship between copper and iron status. The available data for selenium include a mean estimate for plasma selenium concentrations of 1.12 μmol/L and values ranging from 0.97 to 1.54 μmol/L, in relatively small studies [40
]. Selenium concentrations in the present study were similar to several studies in healthy adults [34
], including New Zealand and Australian women [12
], but were lower than levels in many selenium-sufficient countries including Canada, Sweden, UK and USA [42
]. Thomson et al.
, reported that a plasma selenium concentration of 1.14 μmol/L is required to achieve maximal glutathione peroxidase activity [12
]; in the present study 33% of participants reached this target concentration. Further assessment of selenium status among this population may be beneficial in order to promote optimal selenium status.
Serum folate concentrations in Australian females aged 14–45 year (the target group for supplementation) have increased from 14.0 nmol/L, in 1993–1996, to 16.7 nmol/L in 2000; and in 2006, levels were 24 nmol/L. The percentage of low folate concentrations decreased from 8.5% to 4.1% [43
], and the present study results showed that only 1.7% have low folate status. The fortification programme in the USA has increased serum and E-folate concentration to levels that are double the projected value [44
] and virtually eliminated folate deficiency [45
]. Over a third of our study participants had serum folate levels associated with a low risk of NTD, defined as E-folate concentrations >906 nmol/L [23
]. Additional studies are needed to characterise the women with E-folate concentration <906 nmol/L and to determine whether they would benefit from additional intakes of folic acid. One of the limitations of the present study is the lack of information on methylenetetrahydrofolate reductase (MTHFR), which is the rate-limiting enzyme in the pathway of one-carbon metabolism. Single nucleotide polymorphisms in MTHFR may influence susceptibility to NTD and other conditions that are associated with folic acid metabolism, and is important in determining E-folate concentrations in response to folic acid intake.
Only one participant in the present study had E-folate concentrations below the recommended 300 nmol/L. Folate fortification in Australia may have been successful in increasing folate status of young women and confirmation will be required from national representative data. Despite the benefits of eradicating folate deficiency there is some evidence in the literature that high folate status may have undesirable effects such as, neurotoxicity and decline in cognitive function and epigenetic programming in utero [46
Mean concentrations of tHcy in the present study were similar [47
] or lower than others in young women [49
] or in a random population sample [50
]. Small doses of folate have been shown to reduce tHcy in a young population [49
] so the high blood folate levels observed in the present study may be protective of hyperhomocysteinaemia, which was found in 2% of women in this study, half of that in previous reports in young women [51
concentrations in the present study were comparable [52
] or lower than concentrations reported in vegans and omnivores [50
]. We found 11.3% of participants with vitamin B12
concentrations <120 pmol/L, and 4.7% with vitamin B12
deficiency, defined as serum MMA concentrations >0.34 μmol/L. In a similar age group reported in NHANES 1999–2002 [54
], ≤3% of the population were vitamin B12
deficient, and marginal deficiency was more common, at approximately 14%–16%. Australian data show that 4.4% of young adults were vitamin B12
]. We found a significant trend for lower serum tHcy and MMA concentrations as quintiles of serum vitamin B12
increased. A study in older Australians found that 22.9% had vitamin B12
< 185 pmol/L [56
] whereas in young women, we found this level to be nearly double (42.1%). The results of the present study suggest that a substantial proportion of young women are deficient in vitamin B12
, potentially during early pregnancy, and the impact on maternal and foetal wellbeing should be considered.
Strengths of the present study include the availability of multiple analyses of micronutrient biomarkers, which allowed for assessing the prevalence of deficiency, and understanding the interrelationship of multiple deficiencies. Limitations of the present study are the lack of analysis of inflammatory markers since infection and low-grade inflammation may be confounders in the interpretation of iron [25
], zinc [57
] and other biomarkers of nutritional status [58
]; the transitional period of folate fortification during the study period; and the potential sample bias due to the selection of volunteers who were prepared to cease taking nutritional supplements prior to their participation in the present study. Despite strict exclusion of participants with any illness, there is the possibility that acute inflammation may have been present.