Issues pertaining to Mg, Zn and Cu in the 2020 Dietary Reference Intakes for Koreans

Mg intake from Korean diet

Mg is abundant in green leafy vegetables, nuts, legumes, and grains, and is also found in dairy products, meat, fish and shellfish, eggs, and fruits [4]. Therefore, sufficient intake of various food groups and plant-based foods could generally avoid concerns about Mg deficiency. Traditional Korean meals consist of rice and soup/stew as staple foods, a protein-based main dish, and vegetable side dishes that are rich in minerals and vitamins. In South Korea, numerous Mg-rich vegetables (such as leafy, stem, and tubal vegetables) are consumed using various recipes such as seasoning raw vegetables, seasoning cooked vegetables, stir-frying, and blanching [5]. However, the consumption of high-energy foods, high-fat animal-based foods, and high-sugar foods has increased due to recent Westernized and global dietary lifestyle comprising busy work and life schedules, while the consumption of plant-based foods has relatively decreased [6, 7]. Due to the recent downward trend of plant-based food intake, the adequacy of Mg intake needs to be assessed. Previously, few studies have evaluated Mg intake in healthy Korean adults. In a previous study of healthy adults, Mg intake for subjects aged 19–64 yrs was about 250–270 mg per day, and the percentage of subjects consuming Mg below the EAR was 50–55% [8]. In a recent study conducted on healthy adults aged 21–69 yrs (n = 80), Mg intake was determined to be 319 mg/day for males and 277 mg/day for females [9]. The percentage of subjects consuming Mg below the EAR was 50% for males and 67.5% for females, indicating a severe deficiency of Mg intake [9]. If more intake evaluations are performed applying the 2020 KDRIs, accumulation of the intake evaluation data over the years and changing trends in Mg intake might be examined in a more comprehensive way.

To date, there has been no report on any representative study investigating Mg intake using the 2020 KDRIs. This may to be due to the lack of database on the Mg content in foods. The insufficient Mg database in foods has been problematic for determining the adequacy of Mg intake and examining the health benefits of Mg. Therefore, establishment of an ongoing database on the Mg contents in natural and commercial foods in Korea is necessary. This will facilitate a representative assessment of Mg intake, similar to other micronutrients such as calcium (Ca), phosphorus (P), sodium (Na), potassium (K) and iron (Fe), which are currently evaluated in representative Korean population groups.

Mg intake from supplements for health and functional purpose

Among the many roles attributed to this mineral, Mg maintains the bone integrity as a component of bone and teeth, stabilizes cell membranes, acts as a coenzyme of diverse enzymes within our body, delivers neural stimulation, and takes part in the synthesis of fat, protein, and nucleic acid [3, 10, 11, 12]. Based on these physiological functions, numerous studies have shown that Mg is related to non-communicable diseases such as hypertension [13], dyslipidemia [14], diabetes [15], and metabolic syndrome [16], in addition to maintaining the skeletal health. However, most previous studies [13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26] examining the relationship between Mg intake and chronic diseases have been conducted outside Korea. Studies applying KDRIs, or national studies that can be used as scientific evidence for establishing KDRIs, are very limited.

With increasing consumer interest in the relationship between food intake and health status, consumption of dietary supplements is popular worldwide, and their use has been steadily increasing. The use of dietary supplements has been reported in 52% adults in the USA [27], 45.1% females and 25.2% males in the UK [28], and 49% adults in Italy [29]. In South Korea, use of dietary supplements among adults was 57.3% using the 2019 Korea National Health and Nutrition Examination Survey (KNHANES) data [30]. With increasing intake of dietary supplements, there is a corresponding increase in the intake of vitamin and mineral supplements, which are difficult to be sufficiently obtained through food consumption [31]. Growing numbers of healthy people are taking dietary supplements, although there is little evidence supporting that they provide protection against non-communicable diseases [32]. Mg is also consumed as a dietary supplement since various health functions of Mg have been reported [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]. However, there is insufficient evidence for the necessity or a guideline of Mg intake for health functionalities.

Considering that no harmful effects of excessive intake through foods have been reported, the UL in the 2020 KDRIs was set through sources other than foods, including dietary supplements [1]. However, in South Korea, there has been no study on Mg intake through dietary supplement sources other than foods, neither is there any reference value for adequate intake. Since the health function of Mg must be verified not only through dietary Mg intake but also through intake of dietary supplement sources other than foods, a study to evaluate Mg intake through dietary supplements needs to be conducted. In the future, accumulation of these scientific evidences will help in establishing the reference values of Mg for UL and/or prevention of chronic diseases.

Zn intakes from foods and supplements, and establishment of the UL

The 2020 KDRIs provide the major food sources of Zn and Zn contents per serving size from Zn rich foods. However, since reports and study results on real Zn intakes of Koreans are limited, the available data are insufficient to accurately determine the DRI levels for Zn. Moreover, the Zn intakes from supplements are yet to be analyzed. Also, the KNHANES does not provide Zn intake levels in South Korea [34, 35]. The mean and median Zn intakes from foods and supplements would be useful for estimating Zn intakes more accurately. In the USA, Zn RDA values for male and female adults are 11 and 8 mg/day, respectively, while the median Zn intakes from only foods are 14 and 10 mg/day, respectively, which considered to lower UL level as lowest level of 23 mg/day on considering Zn supplements. Zn UL for KDRIs is established as 35 mg/day [36, 37]. The primary reason that Zn UL for South Koreans are higher than the USA levels is because Zn intake from foods and Zn supplements is lower in South Koreans as compared to Americans, which results in obtaining higher Zn UL (35 mg/day). Currently, the UL for Zn needs to be reconsidered since insoluble mineral toxicity is of concern for public health. Particularly, Zn intake from supplements needs to be cautiously considered for children and the elderly due to potential sensitivity to extra high Zn intake. Also, the pattern of food consumption in South Korea has transformed from plant- and grain-oriented foods to animal-oriented foods rich in Zn [6, 34]. Therefore, future KDRIs for Zn need to be prepared based on actual food consumption and Zn supplement data.

Limitations for Zn human studies

The most difficult aspects for estimating the Zn KDRIs are limited human and clinical Zn studies in South Korea and globally. In the past decade, while knowledge about the biochemical and molecular function of Zn has developed and expanded worldwide, reports on large-scale human Zn studies remain limited since the late 1990s [38].

Major clinical outcomes of Zn deficiency include growth retardation, immune dysfunction, the altered cognition ability, altered host defense properties, defects in carbohydrate utilization, etc. This implies the necessity of human studies to elucidate Zn functions and intake levels, in addition to animal studies [39, 40, 41]. Any indications of Zn deficiency and outcomes of Zn balance studies on human subjects are ‘factors’ that need to be considered when estimating the Zn requirement. Without sufficient data and study results, there are limitations for determining accurate Zn requirement. Particularly, dietary Zn human studies for Koreans are very limited and hence insufficient for the accurate determination of Zn intake levels. There are two comprehensive Zn expert working groups for Zn requirements: the Zn group in European Micronutrient Recommendations Aligned (EURRECA) network [42, 43], and the Zn group of the Biomarkers of Nutrition for Development (BOND) project [44]. Reports from both groups provide best practice guidelines for assessing dietary Zn intake and Zn status. Moreover, both groups provide valuable data for establishing the dietary Zn recommendation, including its factorial approach and physiological requirements [45]. However, there are only a few studies capable of compiling Zn intake for a global large-scale human subject study [46, 47].

Reliability of Korean Cu intake assessment

A limited number of studies have assessed the amount of Cu intake by Koreans. The KNHANES, a national survey that evaluates the nutritional status of Koreans, has only evaluated intakes of Ca, P, Na, K, and Fe among minerals. This is because of the paucity of information and incomplete database of Cu content for frequently consumed foods. Currently, the national food composition table of Korea provides Cu information for only 1,639 (54.6%) of the 3,000 food items consumed [33]. Also, this database has adopted information from foreign databases, which might be different in Cu content due to geographical variations in soil and water [52].

Most studies using available Cu database in Korea have reported excess intake over RNI [52, 53, 54, 55]. In a study using data from the 2007–2008 KNHANES, Cu intakes for males and females over the age of 19 years were found to be 1.4 mg/day and 1.1 mg/day, respectively [53]. In a study on Cu consumption by age groups, Cu intakes of Korean males were 1.17, 1.10, 1.33, 1.33, and 1.34 mg/day for the age groups 19–29, 30–39, 40–49, 50–59, and 60 years and over, respectively [55]. In the same study, Cu intakes by Korean females were determined to be 1.07, 1.06, 1.20, 1.29, and 1.36 mg/day for the age groups 19–29, 30–39, 40–49, 50–59, and 60 years and over, respectively, exceeding the recommended intake for both genders [55]. However, since the Cu database covered only 59.2% of food items investigated by Lee et al. [55], it is highly likely that Cu was underestimated due to incomplete data. Considering that most studies report Cu consumption above the RNI, it can be speculated that Cu insufficiency is scarce in Korea.

Cu intake from supplements

Cu intake through food and/or supplement is suggested to be associated with prevalence of certain diseases such as cardiovascular disease and diabetes [56, 57]. However, data on the actual consumption in Korea, through sources other than food, are very limited. Although the risk of excessive Cu intake from diet is very low, it is currently premature to exclude the possibility of excessive Cu intake from supplements. Therefore, establishment of a complete database of Cu in commonly consumed foods and various dietary supplements is needed for a reliable evaluation of Cu intake in Korea, and investigating the relationship between Cu intake and the risk of various chronic diseases.

Reliable biomarkers for Cu status assessment are necessary

To date, KDRIs have mainly relied on insufficient and outdated scientific evidence from 1980’s [58]. In the absence of ‘gold standard’ biomarkers to assess marginal or short-term Cu deficiency, it has been challenging to determine the Cu status. In order to accurately determine adequate Cu consumption and intestinal absorption, there is an immediate requirement of intensive practical and clinical Cu-depletion and/or Cu-repletion studies. Since sensitive clinical biomarkers to determine marginal Cu deficiency or excess Cu have yet to be identified [59], clinical and pre-clinical trials are required to find reliable markers for the Cu status. Several biological markers (ceruloplasmin activity, erythrocyte SOD1, Cu chaperone for SOD1 [CCS] in red blood cells, and peptidylglycine alpha-amidating monooxygenase [PAM]) might be useful for determining moderate to severe Cu deficiency [60, 61]. In the future, we may determine the biological sensitivity of Cu assessing markers to determine the marginal and excess Cu status.

Associated biological relationships between Cu and other divalent metals

In the future, significant scientific effort is required not only to discover robust biological markers for dietary Cu status, but also to understand the physiological interactions between dietary or supplemental Cu and other divalent metals. To date, Cu homeostasis is known to be closely associated with other divalent metal ions such as Zn and Fe. High levels of Zn exposure result in decreased Cu absorption and perturb the whole-body Cu homeostasis [62, 63]. Excess Zn in enterocyte induces metallothionein expression, which inherently possesses higher affinity for Cu than Zn. Therefore, bioavailability of Cu may be significantly suppressed due to metallothionein-mediated Cu being entrapped in enterocytes.

Fe is another divalent metal that strongly interacts with dietary Cu. In Fe deficiency, Cu absorption and utilization are remarkably increased due to elevated intestinal Cu transport and hepatic ceruloplasmin synthesis [59], both clinically [64] and pre-clinically [65, 66]. Conversely, excess Fe exposure suppresses the Cu homeostasis in infants [64, 67, 68] and rapidly growing rodents [65, 66, 69, 70]. Due to competitive interactions among divalent minerals in their intestinal absorption, distribution, and metabolism, the dietary Cu absorption and distribution might be enhanced or reduced by other divalent metal consumptions. Due to limited literature, current Cu KDRIs solely relied on the extrapolation from a sole clinical report [71]. Therefore, to determine the optimal potential Cu DRI, there is a requirement to update Cu repletion/depletion studies by considering interactions with other minerals.