Abstract
Background
This study aims to systematically review the effects of maternal vitamin and/or mineral supplementation on the content of breast milk.
Methods
We systematically searched electronic databases including Medline via PubMed, Scopus and ISI Web of Science till May 24, 2018. The following terms were used systematically in all mentioned databases: (“human milk” OR “breast milk” OR “breast milk composition” OR “human breast milk composition” OR “composition breast milk” OR “mother milk” OR “human breast milk” OR “maternal milk”) AND (“vitamin a” OR “retinol” OR “retinal” OR “retinoic acid” OR “beta-carotene” OR “beta carotene” OR “ascorbic acid” OR “l-ascorbic acid” OR “l ascorbic acid” OR “vitamin c” OR “vitamin d” OR “cholecalciferol” OR “ergocalciferol” OR “calciferol” OR “vitamin e” OR “tocopherol” OR “tocotrienol” OR “alpha-tocopherol” OR “alpha tocopherol” OR “α-tocopherol” OR “α tocopherol” OR “vitamin k” OR “vitamin b” OR “vitamin b complex” OR “zinc” OR “iron” OR “copper” Or “selenium” OR “manganese” OR “magnesium”) and we searched Medline via Medical subject Headings (MeSH) terms. We searched Google Scholar for to increase the sensitivity of our search. The search was conducted on human studies, but it was not limited to the title and abstract. Methodological quality and risk of bias of included studies were evaluated by Jadad scale and Cochrane risk of bias tools, respectively.
Results
This review included papers on three minerals (zinc, iron, selenium) and 6 vitamins (vitamin A, B, D, C, E and K) in addition to multi-vitamin supplements. Although studies had different designs, e.g. not using random allocation and/or blinding, our findings suggest that maternal use of some dietary supplements, including vitamin A, D, vitamin B1, B2 and vitamin C might be reflected in human milk. Vitamin supplements had agreater effect on breast milk composition compared to minerals. Higher doses of supplements showed higher effects and they were reflected more in colostrum than in the mature milk.
Conclusion
Maternal dietary vitamin and/or mineral supplementation, particularly fat- soluble vitamins, vitamin B1, B2 and C might be reflected in the breast milk composition. No difference was found between mega dose and single dose administration of minerals.
Similar content being viewed by others
Background
Human milk is known as the most convenient and available food source for infants in the first 6 months of life. Consuming breast milk should be continued until the end of the second year of an infant’s life with suitable complementary foods. Human milk has a substantial effect on infant growth and development [1, 2]. Consequently, study on the composition of human milk is of crucial importance.
Maternal breast milk composition usually depends on maternal nutrition [3, 4], as has been indicated in previous studies [2,3,4,5]. A systematic review found that maternal dietary intake, particularly fatty acids, and some micronutrients, such as fat-soluble vitamins, vitamin B1 and C, was associated with micronutrient content in breast milk [2].
Micronutrients and vitamins are also very important factors for the development and growth of infants. Micronutrients and vitamins have a profound effect on the neural development of children, metabolic processes, development of soft tissues and muscles, transport of oxygen and synthesis of DNA. Micronutrients and vitamins also have anti-infectious effects and anti-oxidant effect, which is very important in infancy [3, 4]. Lack of some of micronutrients and vitamins cause some diseases such as rickets and vitamin d, hemolytic anemia and also severe anemia with iron, hydrocephalus and vitamin B12, xerophthalmia and vitamin A and recurrent infectious diseases with vitamin A and E [6, 7].
Many studies have been done on the composition of human milk and comparing human milk composition with infant formula. Unlike infant formula which has a standard and fixed composition, human milk composition varies due to factors such as maternal age, maternal parity, nutritional factors, behavioral factors, maternal hormones, environmental factors, infant sex, time of lactation and many other factors [8, 9]. One of the biggest impacts on human milk composition is maternal nutritional status and diet. Many studies have investigated the effect of the amount and type of foods and supplements, such as micronutrients and vitamins that were consumed by mothers, and their effect on human milk. The results of these surveys were widely varied and occasionally contrasting. Maternal diet can influence her milk combination by different metabolic pathways that produce indirect effects and also some metabolic pathways regulate certain human milk combination directly through dietary intake [9,10,11].
In our recently published systematic review by on the effect of maternal diet on human milk composition [2], we found that the association for some elements were stronger including fatty acids and an attenuated association was found with fat soluble vitamins, vitamin B1, and vitamin C. The effects of maternal nutrition on breast milk composition are not the same in all components of macro- and micronutrients; therefore, the question is raised whether maternal supplement use can affect milk composition more than maternal diet.
Another study conducted on Nigerian mothers and their infants at birth and 6 month, showed that concentrations of fatty acids and vitamins such as vitamins A, C, and B6 reflected the respective dietary intakes of these nutrients in the maternal diet [12]. Conversely some other studies showed that the mineral content of human milk is generally considered less related to maternal dietary intakes [13,14,15].
Previous results on the effect of maternal micronutrients and vitamin intake on human milk are contradictory. Therefore, this study aims to systematically review the effects of maternal vitamin and/or mineral supplementation on breast milk content.
Methods
The review study was designed in accordance with the protocols of Systematic Review and Meta-Analysis (PRISMA) [16]. The study protocol is registered in the PROSPERO with identification number of CRD42020209008.
Literature search
We systematically searched the electronic databases including Medline via PubMed, Scopus and ISI Web of Science till May 24, 2018. The following key words were used systematically in all mentioned databases: (“human milk” OR “breast milk” OR “breast milk composition” OR “human breast milk composition” OR “composition breast milk” OR “mother milk” OR “human breast milk” OR “maternal milk”) AND (“vitamin a” OR “retinol” OR “retinal” OR “retinoic acid” OR “beta-carotene” OR “beta carotene” OR “ascorbic acid” OR “l-ascorbic acid” OR “l ascorbic acid” OR “vitamin c” OR “vitamin d” OR “cholecalciferol” OR “ergocalciferol” OR “calciferol” OR “vitamin e” OR “tocopherol” OR “tocotrienol” OR “alpha-tocopherol” OR “alpha tocopherol” OR “α-tocopherol” OR “α tocopherol” OR “vitamin k” OR “vitamin b” OR “thiamin” OR “vitamin B1” OR “vitamin B12” OR “vitamin B6” OR “vitamin B7” OR “vitamin B3” OR “vitamin B2” OR “vitamin b complex” OR “thiamine” OR “riboflavin” OR “niacin” OR “pantothenic acid” OR “pyridoxine” OR “biotin” OR “folate” OR “cobalamin” OR “zinc” OR “iron” OR “copper” OR “selenium” OR “manganese” OR “magnesium”).
Furthermore, we searched Medline via Medical subject Headings (MeSH) terms with following MeSH terms: (“Milk, Human”[Mesh]) AND (“Vitamin A”[Mesh] OR “Ascorbic Acid”[Mesh] OR “Vitamin D”[Mesh] OR “Vitamin E”[Mesh] OR “Vitamin K”[Mesh] OR “Vitamin B Complex”[Mesh] OR “Vitamin K 3”[Mesh] OR “Vitamin K 2”[Mesh] OR “Vitamin K 1”[Mesh] OR “Vitamin B 12”[Mesh] OR “Vitamin B 6”[Mesh] OR “Zinc”[Mesh] OR “Iron”[Mesh] OR “Copper”[Mesh] OR “Selenium”[Mesh] OR “Manganese”[Mesh] OR “Magnesium”[Mesh] OR “Thiamine”[Mesh] OR “Riboflavin”[Mesh] OR “Niacin”[Mesh] OR “Pantothenic Acid”[Mesh] OR “Pyridoxine”[Mesh] OR “Biotin”[Mesh] OR “Folic Acid”[Mesh] OR “Vitamin B 12”[Mesh]).
Also, we searched Google scholar to increase the sensitivity of our search. The search was conducted on human studies, but it was not limited to title and abstract because our desired results or outcomes might have been considered a secondary aim of the studies and mentioned in the full text of articles. Limitations were applied to exclude conference papers, editorials, letters, commentary, short surveys, and notes. We did not consider any time limitation. Only English papers were used in the current review.
Hand searching
We checked the reference list of the published studies to increase the sensitivity and to identify more related studies.
Ethical consideration
Ethical approval was not required as this was a secondary study.
Data management
We used EndNote program (version 6) for managing and handling extracted references that were searched from databases. Duplicates were removed and entered into a duplicate library.
Selection criteria
Studies identified from the literature search were selected on the basis of the predefined selection criteria presented later:
Inclusion criteria
-
1-
All interventional studies (randomized controlled trial, quasi experimental)
-
2-
Studies that have studied the effect of any nutrient (macro or micro) and/or (?) supplements on human milk composition.
-
3-
Studies assessing the composition of mother’s milk.
Exclusion criteria
-
1.
Conference papers, editorials, letters, commentary, short surveys, and notes
-
2.
Animal studies
-
3.
Laboratory studies
-
4.
Studies that have studied the effect of any nutrient intake (macro or micro) and/or supplements on blood serum of mothers or infants (only the effect of nutritional supplements on milk composition were included).
-
5.
Studies that used fortified foods, vegetables and/or fruits (oranges, carrots, etc.) rather than dietary supplements.
Assessment of study quality
For quality assessment we used Jadad scale for classification and ranking the methodological quality of eligible studies [17]. According to the study design such as randomization and blinding, each study was classified with a score ranging from 0 to 5, and studies with Jadad score above 3 were considered a high quality study.
Quality of included studies and risk of bias assessment
Quality assessment of each included study according to Jadad scale is demonstrated in the last column of Tables 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. Also, Figs. 1 and 2 show risk of bias item presented as a percentage and risk of bias item for each included study, respectively.
Risk of bias graph review: authors’ judgements on each risk of bias item presented as a percentage for each included study
Risk of bias summary review: authors’ judgements on each risk of bias item for each included study
Risk of bias assessment
We assessed the quality of the included studies using the risk of bias assessment tools developed by the Cochrane Collaboration [1], covering the following six domains: sequence generation, allocation concealment, blinding, incomplete data, selective reporting, and other bias. Two reviewers independently conducted the risk of bias evaluation and resolved any disagreement by discussion with a third reviewer. The reviewers’ judgment is categorized as ‘Low risk’, ‘High risk’ or ‘Unclear risk’ of bias.
RevMan (version 5.3) software was used for graphical display of risk of bias of included studies.
Data extraction and abstraction
We retrieved 4046 unique references after removing duplicates (in the basic search 1971 articles were duplicates that were found and removed using EndNote, Fig. 3). Of them, 3034 were excluded on the basis of the title and abstract. For the remaining 1012 articles, the full text was retrieved and critically reviewed. After the selection process, 67 papers were included in this systematic review.
Papers search and review flowchart for selection of primary studies
Two independent reviewers (MK and RS) screened the titles and abstracts of papers, which were identified by the literature search, for their potential relevance or assessed the full text for inclusion in the review. In the case of disagreement, the discrepancy was resolved in consultation with an expert investigator (RK).
Two reviewers abstracted the data independently (MK and RS). The required information that was extracted from all eligible papers was as follows: data on first author’s family name, year of publication, country of the study, type of supplement or food, characteristics of participants, type of study, aim, type of nutrients evaluated in the milk and the main findings of studies. Accordingly, because of the importance of the study areas, as shown in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, we have provided the WHO regions for countries where the studies were conducted. These areas including; Western Pacific Regional Office (WPRO), South East Asia (SEARO), Europe (EURO), Eastern Mediterranean (EMRO), Americas (AMRO), Africa (AFRO).
Results
In total, 67 paper were included in the current review; zinc (3 papers) [15, 71, 72], iron (4 papers) [79,80,81,82], selenium (6 papers) [73,74,75,76,77,78], vitamin A (26 papers) [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43], vitamin B (8 papers) [44,45,46,47,48,49,50,51], vitamin C (2 papers) [52, 53], vitamin D (6 papers) [54,55,56,57,58,59], vitamin E (6 papers) [33, 60,61,62, 64, 83], vitamin K (3 papers) [63, 65, 66], and multiple vitamins (5 papers) [29, 67,68,69,70].
Effect of mineral supplements on breast milk composition
In total, three minerals including zinc (3 papers), iron (4 papers) and selenium (6 papers) were reviewed. The summary of the effect of mineral supplements on breast milk content is presented in Tables 8, 9 and 10. Some findings are mentioned here, briefly.
Zinc
Two studies showed that zinc supplementation for lactating women positively influenced breast milk zinc levels [15, 72] and maternal body stores [72]. However, another study found that the milk zinc level decreased significantly for all lactating women, and there was no significant difference in the rate of declining zinc levels between women who started supplementation during lactation and those who were not supplemented [71].
Iron
Most studies found that iron supplementation did not significantly change iron levels of milk [80,81,82]. However, iron supplementation increased the total iron ligands in breast milk, measured by total iron-binding capacity and increased the proportion of lactoferrin in total protein secreted [81]. Breast milk lactoferrin levels seemed to be higher among supplemented women [81].
Selenium
Most studies showed that selenium supplementation increased breast milk selenium levels [73, 74, 76,77,78]; however, a recent study found that selenite supplementation was not related to a change of plasma or breast milk selenium concentrations [75].
Effect of vitamin supplements on breast milk composition
In total, six vitamins including vitamin A, B, D, C, E and K in addition to multi-vitamin supplements were reviewed. The summary about the effect of vitamin supplements on breast milk content is presented in Tables 1, 2, 3, 4, 5, 6 and 7. Here, we mention some findings in brief.
Vitamin A
In total, 26 studies investigated the effect of vitamin A or its different supplementary forms including retinol, red palm oil (rich in pro-vitamin A), retinylpalmitate, β-carotene, and retinol palmitate on breast milk content. Vitamin A supplementation resulted in significantly increased retinol content, or α and β-carotene concentrations of breast milk in most studies [18,19,20,21,22,23,24,25, 27, 30, 31, 33, 35,36,37,38,39, 41, 42]. However, some studies found no association of vitamin A supplementation on breast milk composition [26, 28, 32, 34, 43].
Vitamin D
Vitamin D supplementation increased 25-hydroxy-D levels of breast milk [54,55,56, 58, 59], but in a recent study no significant incremental change was observed in 25 (OH) D levels of breast milk, however, change in 25 (OH) D levels in breast milk in the vitamin D supplemented group was significantly different from that of the placebo group [57].
Vitamin B
Dietary supplementation with vitamin B group, including B1 [47], B2 [47], B6 [45] and B12 [46, 49] was associated with increased levels of these vitamins in breast milk, however, no significant differences were observed for thiamin [48], and B12 [48] in some studies.
Vitamin C
Vitamin C supplementation resulted in a significantly higher ascorbic acid level in human milk [53], however in another study there was no significant change in maternal milk after vitamin C supplementation [52].
Vitamin K
Vitamin K supplemented groups had significantly higher vitamin K (phylloqinone) milk concentrations in most studies [63, 65, 66].
Vitamin E
Breast milk α-tocopherol levels increased after supplementation in the intervention group [62, 64, 83], however, no significant time-dependent changes were observed in breast milk [61]. Maternal supplementation with 400 international units of RRR, α, tocopherol increased vitamin E concentrations of the colostrum and transitional milk [60, 64, 83] but not of the mature milk [83].
Multiple vitamins
Significant increases were observed in the retinol and α-tocopherol levels of the colostrum among women who received vitamin A [68]. β-carotene supplementation did not significantly change the milk β-carotene concentrations, other carotenoids, retinol or tocopherol [29, 67] and retinol [67]. However, it is also reported that β-carotene supplementation might increase the mean β-carotene content of milk [67]. Another study showed that daily vitamin A and β-carotene supplementation during pregnancy and lactation resulted in increased retinol, β-carotene and α-carotene content of human milk at all time points during the first year postpartum [70]. However, supplementation with multi-vitamin (thiamin, riboflavin, vitamin B6, niacin, vitamin B12, vitamin C and E) was not associated with changes of β-carotene content, but it significantly decreased the γ- tocopherol levels of human milk at all times during lactation, and also reduced the retinol levels at delivery [70].
Previous systematic reviews
Based on our search in the mentioned databases, we found no comprehensive study quantifying the effects of dietary supplements including vitamins and minerals on breast milk composition. We found few systematic reviews on the effects of vitamin D [84], vitamin A [85], and vitamin K supplements on breast milk composition [86]. Additionally, two studies examined the effects of maternal nutrition and diet on breast milk composition, but not the effects of supplements on breast milk composition [2, 13].
Risk of bias of the included studies
According to Fig. 1, we found that the most common bias was related to random sequence generation and blinding. Also, allocation concealment was the most unclear risk of bias. The least bias included attrition bias and reporting bias.
Discussion
This study systematically reviewed the effect of mineral and vitamin supplementation on breast milk composition. Different randomized controlled trials revealed the possible effect of maternal supplementation on breast milk content.
Breast milk of healthy, well-nourished mothers contains almost all the necessary nutrients for an infant’s growth and development. Association of maternal dietary supplements and milk composition might reflect the nutrient metabolism, since many ingredients of human milk are derived from maternal blood. In addition, understanding the effect of maternal nutrient supplementary intake on breast milk composition seems important, because almost all pregnant and lactating mothers receive supplements.
Previous studies have mostly focused on the effect of single vitamin or mineral supplementation on breast milk, while there is no comprehensive review on the effect of various vitamin and/or mineral supplementation during pregnancy and lactation and its impact on maternal milk composition.
Vitamin A supplementation and breast milk
Randomized controlled trials evaluating the effect of postpartum maternal vitamin A supplementation indicated a significant improvement in maternal serum retinol, breast milk retinol and vitamin A liver stores, after single dose of vitamin A supplementation.
Vitamin A supplementation might be given in different formulations including vitamin A, measured in retinol units (IU) of retinylpalmitate, water miscible formulation or β-carotene. Synthetic β-carotene supplements resulted in improved breast milk vitamin A content, compared with dietary intake of β-carotene [87]. There is controversy regarding the duration of vitamin A supplementation, possibly due to the different breast milk collection methods. It has been suggested that although vitamin A supplementation did not show any adverse side effects, but this might not apply for women and infants from well-nourished populations [87].
Type of interventions were different between studies, including maternal vitamin A supplementation (β-carotene or retinylpalmitate or water miscible formulation) alone or in combination with other micro-nutrients (iron, folic acid, vitamin E) in comparison with placebo, no intervention, other micro-nutrient or a low dose of vitamin A [87]. In addition, co-existing vitamin A, zinc and iron deficiencies are common nutritional problems and evidence suggests that zinc status affects some aspects of vitamin A metabolism such as absorption, transportation and its usage [87].
It has been suggested that the baseline vitamin A status of breast milk might affect the results of supplementation studies [87]. Continued exclusive breastfeeding for 6 months indicated a greater cumulative need for vitamin A compared to mothers who give only 1, 2 or 3 breastfeeds per day. In addition, the follow up pattern of subjects with initial normal or high values of vitamin A is different from those with already low values at starting time [87]. Moreover, some studies did not clarify the techniques used for maternal milk collection or which breast was used, and time of milk collection was also not considered. Some studies suggest that it was not possible to distinguish between full-breast sample collection and on-demand collection [87].
As vitamin A is fat-soluble and carried in lipid phase, the variability of fat content of milk needs to be considered. This might also result in sampling errors due to non-standardized collection methods. This error could also be explained by the content of the breast from which the sample collection occurred; fuller breast usually have lower fat content [87, 88]. Moreover, fat content of milk which affects vitamin A concentrations is related to the time of day that samples are taken. Consistently, previous studies indicated greater agreement for lipid content in maternal milk collected between 6 AM and 8 AM of fasting women and greater variation in breast milk collected between 12 noon and 2 PM, and between 4 PM and 6 PM. This may explain differences between study findings without appropriate homogenization of procedures [89].
Vitamin D supplementation and breast milk
The vitamin D content of human milk is completely variable and might be affected by season, maternal dietary intake of vitamin D, and ethnicity. Most previous studies have demonstrated that maternal vitamin D supplementation increased vitamin D content of human milk [54,55,56, 58, 59], but a recent study found no significant changes in breast milk 25 (OH) D levels [57]. It seems that as mothers provided milk samples at different time points including months 1, 2, 3 and 4 of lactation, this could have affected the study results. Also, recent evidence has shown that there is a possibility of correlation between some minerals and levels of vitamin D [90,91,92].
Thiamin and riboflavin supplementation and breast milk
The main form of thiamin in milk is thiamin-monophosphate (TMP) with some free thiamin [93, 94], while flavin adenine dinucleotide (FAD) is the main source of riboflavin, in addition to free riboflavin and few amounts of other flavin compounds [95]. However, little is known about mechanisms related to the transport of vitamins B1 and B2 to breast milk or possible alterations of vitamer uptake due to supplementation. Previous studies reported that maternal thiamin supplementation resulted in higher thiamin content of breast milk [96], however, it seems that thiamin is transferred into breast milk in limited amounts [96]. Previous research in the US indicated no effect of thiamin supplementation on breast milk of well-nourished women [97, 98]. In addition, breast milk collected at 10 weeks will have considerably lower amounts of total thiamin compared to milk collected at 6 weeks [99].
The amounts of phosphorylated vitamers might either decrease or not change over time, therefore possible phosphorylation of thiamin, hydrolysis of thiamin pyrophosphate (TPP) or secretion of thiamin monophosphate (TMP) might be up-regulated in the early phase of lactation [47]. Among all vitamers of thiamin in human milk, only free thiamin levels increased during lactation which suggests an active transport of this vitamer to mammary glands. The major vitamer, TMP, might transport actively into the milk, but could also be found as a phosphorylation process of free thiamin or hydrolysis of TPP. Transportation, phosphorylation or hydrolysis processes might be up-regulated in the early stages of lactation.
Riboflavin supplementation is associated with higher levels of vitamin B2 in maternal milk [44, 96]. Free riboflavin is generally used in supplements, thus a greater increase in this vitamer is expected which suggests its efficient absorption and transport to breast milk, rather than conversion to its co-enzymatic forms prior to secretion. Supplementation might increase free riboflavin content of maternal milk, but not necessarily FAD levels, suggesting a favorable secretion of its free forms to breast milk [47]. More research is needed for a better understanding of mechanisms for vitamin secretion to maternal milk, factors associated with vitamer conversion in the mammary glands and the role of vitamers.
Vitamin C supplementation and breast milk
Little is known about the impact of increased intake of vitamin C on human milk. Previous reports demonstrated that increased intake of vitamin C in women with low maternal vitamin C content at baseline, might increase vitamin C levels of human milk [52, 53, 100]. In a previous study, a relatively high dose of vitamin C caused a modest response among European women compared to a 3-fold increase in mean human milk vitamin C levels of African women [53]. It has been suggested that there is an upper limit for ascorbic acid secreted by the mammary glands, possibly due to the saturation of the gland with vitamin C [52, 100], however, the mechanism related to the regulation of ascorbic acid saturation and secretion by the glands are not completely understood. Differences between study findings suggest that there is significant variation in breast milk ascorbic acid content of individuals living in different regions. Moreover, milk samples were collected at different times, and the amount of milk expressed at each sampling varied. Lack of access to modern analytic techniques such as HPLC was another possible explanation; simple methods such as titration measures only reduced vitamin C (ascorbic acid) and not the total ascorbic acid. Based on previous studies, the dehydro-ascorbic acid level of human milk is lower than its reduced ascorbic content [53]. Dietary intake data was not collected in some studies, and urinary excretion of ascorbic acid was not monitored, as well [52, 53, 100].
Vitamin E supplementation and breast milk
Studies on the effect of maternal vitamin E supplementation on breast milk are scarce and inconclusive; some reported a correlation between supplementation and breast milk vitamin E levels and some did not [60, 101, 102]. Maternal supplementation with R, R, R, α-tocopherol increased vitamin E levels of colostrum and transitional milk, but not the vitamin E of mature milk [102].
The positive effect of vitamin E supplementation on colostrum and transitional milk might be explained by increased synthesis of fatty acids by the mammary gland in the first few days after childbirth [103], due to the role of vitamin E in lipid metabolism. The mechanisms responsible for vitamin E transfer into breast milk have not been completely clarified, but it seems that α-tocopherol reaches the milk via LDL receptors [102, 104].
Previous studies indicated that vitamin E transportation to breast milk through independent and distinct mechanisms and limited by receptors, because maternal serum α-tocopherol content is not related to colostrum α-tocopherol levels [105]. Michaelis-Mentenkinetics is another hypothesis for α-tocopherol transfer to breast milk. This could transport vitamin E to the mammary gland regardless of its plasma levels [106, 107].
Some limitations of previous studies are as follows; reduced number of initial participants, and loss to follow up for analysis of α-tocopherol in mature milk. In addition, different dietary habits might explain differences between study groups [102]. The results provide evidence on the importance of maternal vitamin E supplementation, especially among women with preterm infants, to meet infant vitamin E requirements and protect them against oxidative stress [102, 108].
However, studies suggest that a single mega dose of 400 IU vitamin E seems not to be enough to increase vitamin E content of breast milk for a prolonged time [102].
Β-carotene supplementation and breast milk
Information is lacking regarding changes in milk carotenoid content of healthy, well-nourished women in the first month of lactation. Role of carotenoids in breast milk is not completely understood. It has been suggested that high levels of carotenoids transferred to infants during the first few days of lactation could correct abnormally low levels of β-carotene in neonates [109]. Other studies have indicated that β-carotene supplementation of lactating mothers could increase the β-carotene content of breast milk [67, 110, 111].
Lack of increase in milk β-carotene content suggests that transitional milk might be saturated with β-carotene. The higher milk lutein levels and subsequent decrease in plasma lutein, suggests that lutein metabolism might be changed in early lactation [29]. The lack of effect of β-carotene supplements on retinol, α-tocopherol and other carotenoid levels of milk are consistent with previous reports [29, 67].
Different results might be explained by different techniques used to measure carotenoid content; before development of HPLC, separation methods reported only total carotenoid content [29], while HPLC technique provided more details on each specific carotenoid level. Moreover, interpretation was limited to small sample size, lack of maternal dietary intake data or lack of milk fat content as a variable. It has also been suggested to consider milk fat variations in milk carotenoid analysis [29, 33, 67, 112].
Limitation and strengths
Because of large heterogeneity between studies, we could not conduct a meta-analysis; however, this comprehensive review provides sufficient information on the effect of maternal vitamin and/or mineral supplementation breast milk composition.
Other underlying factors including significant individual variation in diet, role of dietary intake data and analysis, over and/or underestimation of dietary intake, milk sample collection method, different dose and forms of supplementations (natural vs. synthetic), different techniques for nutrient measurements, race and/or ethnicity, postpartum milk sampling, time of milk sampling, baseline nutrient level of breast milk, and duration of breastfeeding, might partly explained the large variation between studies. Maternal baseline nutritional status might be considered prior to supplementation. In addition, some methodological differences between studies, including not using random allocation and/or blinding as an important part of a clinical trial, might affect study results.
Limitations of the Jadad score
Considering three criteria (randomization, double-blinding, and a description of dropouts), the Jadad scale, is a common tool used to summarize quality measures of randomized controlled trials (RCTs). However, the Jadad scale has its limitations [113, 114]. First, the double blinding criterion is usually reported in around 10 to 20% of studies. Moreover, although the double blinding criterion accounts for 40% of the Jadad score, it is suggested that many trials involve devices, physical training, surgery, or other interventions e.g. exercise training for which double blinding is either impractical or impossible. In addition, the Jadad score does not assess the appropriateness of the data analysis, or allocation concealment, or of intention to treat, among other glaring deficiencies [115, 116].
Conclusion
In conclusion, studies with different designs, e.g. not using random allocation and/or blinding, found that maternal dietary vitamin and/or mineral supplementation, particularly fat soluble vitamins, vitamins B1, B2 and C were reflected in breast milk composition. Moreover, vitamin supplements had greater effects on the breast milk composition compared to minerals. Higher dose of supplements showed more effects, and they were reflected in colostrum more than in mature milk. No difference was found between amega dose and a single dose administration of minerals.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Innis SM. Impact of maternal diet on human milk composition and neurological development of infants. Am J Clin Nutr. 2014;99(3):734s–41s.
Keikha M, Bahreynian M, Saleki M, Kelishadi R. Macro- and micronutrients of human milk composition: are they related to maternal diet? A comprehensive systematic review. Breastfeed Med. 2017;12(9):517–27.
Ortega RM, Lopez-Sobaler AM, Martinez RM, Andres P, Quintas ME. Influence of smoking on vitamin E status during the third trimester of pregnancy and on breast-milk tocopherol concentrations in Spanish women. Am J Clin Nutr. 1998;68(3):662–7.
Kodentsova VM, Vrzhesinskaya OA. Evaluation of the vitamin status in nursing women by vitamin content in breast milk. Bull Exp Biol Med. 2006;141(3):323–7.
Shea MK, Booth SL. Concepts and controversies in evaluating vitamin k status in population-based studies. Nutrients. 2016;8(1):8.
Fransson GB, Agarwal KN, Gebre-Medhin M, Hambraeus L. Increased breast milk iron in severe maternal anemia: physiological “trapping” or leakage? Acta Paediatr Scand. 1985;74(2):290–1.
Ahmad SM, Hossain MI, Bergman P, Kabir Y, Raqib R. The effect of postpartum vitamin a supplementation on breast milk immune regulators and infant immune functions: study protocol of a randomized, controlled trial. Trials. 2015;16:129.
Krebs NF, Reidinger CJ, Hartley S, Robertson AD, Hambidge KM. Zinc supplementation during lactation: effects on maternal status and milk zinc concentrations. Am J Clin Nutr. 1995;61(5):1030–6.
Domellof M, Lonnerdal B, Dewey KG, Cohen RJ, Hernell O. Iron, zinc, and copper concentrations in breast milk are independent of maternal mineral status. Am J Clin Nutr. 2004;79(1):111–5.
Novak EM, Innis SM. Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism. Am J Physiol Endocrinol Metab. 2011;301(5):E807–17.
Dorea JG. Selenium and breast-feeding. Br J Nutr. 2002;88(5):443–61.
Murray MJ, Murray AB, Murray NJ, Murray MB. The effect of iron status of Nigerien mothers on that of their infants at birth and 6 months, and on the concentration of Fe in breast milk. Br J Nutr. 1978;39(3):627–30.
Bravi F, Wiens F, Decarli A, Dal Pont A, Agostoni C, Ferraroni M. Impact of maternal nutrition on breast-milk composition: a systematic review. Am J Clin Nutr. 2016;104(3):646–62.
Hollis BW, Pittard WB 3rd, Reinhardt TA. Relationships among vitamin D, 25-hydroxyvitamin D, and vitamin D-binding protein concentrations in the plasma and milk of human subjects. J Clin Endocrinol Metab. 1986;62(1):41–4.
Krebs NF, Hambidge KM, Jacobs MA, Rasbach JO. The effects of a dietary zinc supplement during lactation on longitudinal changes in maternal zinc status and milk zinc concentrations. Am J Clin Nutr. 1985;41(3):560–70.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.
Ayah RA, Mwaniki DL, Magnussen P, Tedstone AE, Marshall T, Alusala D, et al. The effects of maternal and infant vitamin a supplementation on vitamin a status: a randomised trial in Kenya. Br J Nutr. 2007;98(2):422–30.
Bahl R, Bhandari N, Wahed MA, Kumar GT, Bhan MK. Vitamin a supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin a status. J Nutr. 2002;132(11):3243–8.
Basu S, Sengupta B, Paladhi PK. Single megadose vitamin a supplementation of Indian mothers and morbidity in breastfed young infants. Postgrad Med J. 2003;79(933):397–402.
Bezerra DS, Araujo KF, Azevedo GM, Dimenstein R. Maternal supplementation with retinyl palmitate during immediate postpartum period: potential consumption by infants. Rev Saude Publica. 2009;43(4):572–9.
Bezerra DS, de Araujo KF, Azevedo GM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin a supplementation on breast milk retinol levels. J Hum Lact. 2010;26(2):148–56.
Bhaskaram P, Balakrishna N, Nair KM, Sivakumar B. Vitamin a deficiency in infants: effects of postnatal maternal vitamin a supplementation on the growth and vitamin a status. Nutr Res. 2000;20(6):769–78.
Canfield LM, Kaminsky RG, Taren DL, Shaw E, Sander JK. Red palm oil in the maternal diet increases provitamin a carotenoids in breastmilk and serum of the mother-infant dyad. Eur J Nutr. 2001;40(1):30–8.
Canfield LM, Taren DL, Kaminsky RG, Mahal Z. Short-term beta-carotene supplementation of lactating mothers consuming diets low in vitamin a. J Nutr Biochem. 1999;10(9):532–8.
Darboe MK, Thurnham DI, Morgan G, Adegbola RA, Secka O, Solon JA, et al. Effectiveness of an early supplementation scheme of high-dose vitamin a versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial. Lancet. 2007;369(9579):2088–96.
Dijkhuizen MA, Wieringa FT, West CE, Muhilal. Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin a status in both mothers and infants. Am J Clin Nutr. 2004;80(5):1299–307.
Garcia-Guerra A, Neufeld LM, Hernandez-Cordero S, Rivera J, Martorell R, Ramakrishnan U. Prenatal multiple micronutrient supplementation impact on biochemical indicators during pregnancy and postpartum. Salud Publica Mex. 2009;51(4):327–35.
Gossage CP, Deyhim M, Yamini S, Douglass LW, Moser-Veillon PB. Carotenoid composition of human milk during the first month postpartum and the response to β-carotene supplementation. Am J Clin Nutr. 2002;76(1):193–7.
Grilo EC, Lima MS, Cunha LR, Gurgel CS, Clemente HA, Dimenstein R. Effect of maternal vitamin a supplementation on retinol concentration in colostrum. J Pediatr. 2015;91(1):81–6.
Grilo EC, Medeiros WF, Silva AG, Gurgel CS, Ramalho HM, Dimenstein R. Maternal supplementation with a megadose of vitamin a reduces colostrum level of alpha-tocopherol: a randomised controlled trial. J Hum Nutr Diet. 2016;29(5):652–61.
Idindili B, Masanja H, Urassa H, Bunini W, van Jaarsveld P, Aponte JJ, et al. Randomized controlled safety and efficacy trial of 2 vitamin a supplementation schedules in Tanzanian infants. Am J Clin Nutr. 2007;85(5):1312–9.
Johnson EJ, Qin J, Krinsky NI, Russell RM. β-Carotene isomers in human serum, breast milk and buccal mucosa cells after continuous oral doses of all-trans and 9-cis β-carotene. J Nutr. 1997;127(10):1993–9.
Klevor MK, Haskell MJ, Lartey A, Adu-Afarwuah S, Zeilani M, Dewey KG. Lipid-based nutrient supplements providing approximately the recommended daily intake of vitamin a do not increase breast milk retinol concentrations among Ghanaian women. J Nutr. 2016;146(2):335–42.
Lietz G, Henry CJ, Mulokozi G, Mugyabuso JK, Ballart A, Ndossi GD, et al. Comparison of the effects of supplemental red palm oil and sunflower oil on maternal vitamin a status. Am J Clin Nutr. 2001;74(4):501–9.
Lietz G, Mulokozi G, Henry JC, Tomkins AM. Xanthophyll and hydrocarbon carotenoid patterns differ in plasma and breast milk of women supplemented with red palm oil during pregnancy and lactation. J Nutr. 2006;136(7):1821–7.
Martins TM, Ferraz IS, Daneluzzi JC, Martinelli CE Jr, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin a supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr. 2010;64(11):1302–7.
Muslimatun S, Schmidt MK, West CE, Schultink W, Hautvast JG, Karyadi D. Weekly vitamin a and iron supplementation during pregnancy increases vitamin a concentration of breast milk but not iron status in Indonesian lactating women. J Nutr. 2001;131(10):2664–9.
Nagayama J, Noda K, Uchikawa T, Maruyama I, Shimomura H, Miyahara M. Effect of maternal Chlorella supplementation on carotenoid concentration in breast milk at early lactation. Int J Food Sci Nutr. 2014;65(5):573–6.
Rice AL, Stoltzfus RJ, de Francisco A, Kjolhede CL. Evaluation of serum retinol, the modified-relative-dose-response ratio, and breast-milk vitamin a as indicators of response to postpartum maternal vitamin a supplementation. Am J Clin Nutr. 2000;71(3):799–806.
Roy SK, Islam A, Molla A, Akramuzzaman SM, Jahan F, Fuchs G. Impact of a single megadose of vitamin a at delivery on breastmilk of mothers and morbidity of their infants. Eur J Clin Nutr. 1997;51(5):302–7.
Stoltzfus RJ, Hakimi M, Miller KW, Rasmussen KM, Dawiesah S, Habicht JP, et al. High dose vitamin a supplementation of breast-feeding Indonesian mothers: effects on the vitamin a status of mother and infant. J Nutr. 1993;123(4):666–75.
Tomiya MT, de Arruda IK, da Silva DA, Santana RA, da Silveira KC, Andreto LM. The effect of vitamin a supplementation with 400 000 IU vs 200 000 IU on retinol concentrations in the breast milk: a randomized clinical trial. Clin Nutr. 2017;36(1):100–6.
Bates C, Prentice A, Watkinson M, Morrell P, Sutcliffe B, Foord F, et al. Riboflavin requirements of lactating Gambian women: a controlled supplementation trial. Am J Clin Nutr. 1982;35(4):701–9.
Chang SJ, Kirksey A. Vitamin B6 status of breast-fed infants in relation to pyridoxine HCl supplementation of mothers. J Nutr Sci Vitaminol (Tokyo). 2002;48(1):10–7.
Duggan C, Srinivasan K, Thomas T, Samuel T, Rajendran R, Muthayya S, et al. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. J Nutr. 2014;144(5):758–64.
Hampel D, Shahab-Ferdows S, Adair LS, Bentley ME, Flax VL, Jamieson DJ, et al. Thiamin and riboflavin in human milk: effects of lipid-based nutrient supplementation and stage of lactation on vitamer secretion and contributions to total vitamin content. PLoS One. 2016;11(2):e0149479.
Hampel D, Shahab-Ferdows S, Islam MM, Peerson JM, Allen LH. Concentrations in human milk vary with time within feed, circadian rhythm, and single dose supplementation. J Nutr. 2017;147(4):603–11.
Siddiqua TJ, Ahmad SM, Ahsan KB, Rashid M, Roy A, Rahman SM, et al. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh. Eur J Nutr. 2016;55(1):281–93.
Styslinger L, Kirksey A. Effects of different levels of vitamin B-6 supplementation on vitamin B-6 concentrations in human milk and vitamin B-6 intakes of breastfed infants. Am J Clin Nutr. 1985;41(1):21–31.
Thomas MR, Kawamoto J, Sneed SM, Eakin R. The effects of vitamin C, vitamin B6, and vitamin B12 supplementation on the breast milk and maternal status of well-nourished women. Am J Clin Nutr. 1979;32(8):1679–85.
Byerley LO, Kirksey A. Effects of different levels of vitamin C intake on the vitamin C concentration in human milk and the vitamin C intakes of breast-fed infants. Am J Clin Nutr. 1985;41(4):665–71.
Daneel-Otterbech S, Davidsson L, Hurrell R. Ascorbic acid supplementation and regular consumption of fresh orange juice increase the ascorbic acid content of human milk: studies in European and African lactating women. Am J Clin Nutr. 2005;81(5):1088–93.
Ala-Houhala M, Koskinen T, Parviainen MT, Visakorpi JK. 25-Hydroxyvitamin D and vitamin D in human milk: effects of supplementation and season. Am J Clin Nutr. 1988;48(4):1057–60.
Basile LA, Taylor SN, Wagner CL, Horst RL, Hollis BW. The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants. Breastfeed Med. 2006;1(1):27–35.
Ketha H, Thacher TD, Oberhelman SS, Fischer PR, Singh RJ, Kumar R. Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio. Bone. 2018;110:321–5.
Niramitmahapanya S, Kaoiean S, Sangtawesin V, Patanaprapan A, Bordeerat N, Deerochanawong C. Correlation of 25-hydroxyvitamin d levels in serum vs. breastmilk in vitamin d-supplementation breastfeeding women during lactation: randomized double blinded control trial. J Med Assoc Thai. 2017;100:S165–71.
Oberhelman SS, Meekins ME, Fischer PR, Lee BR, Singh RJ, Cha SS, et al. Maternal vitamin D supplementation to improve the vitamin D status of breast-fed infants: a randomized controlled trial. Mayo Clin Proc. 2013;88(12):1378–87.
Wall CR, Stewart AW, Camargo CA Jr, Scragg R, Mitchell EA, Ekeroma A, et al. Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy. Am J Clin Nutr. 2016;103(2):382–8.
Clemente HA, Ramalho HM, Lima MS, Grilo EC, Dimenstein R. Maternal supplementation with natural or synthetic vitamin E and its levels in human colostrum. J Pediatr Gastroenterol Nutr. 2015;60(4):533–7.
Gaur S, Kuchan MJ, Lai CS, Jensen SK, Sherry CL. Supplementation with RRR- or all-rac-alpha-Tocopherol differentially affects the alpha-tocopherol stereoisomer profile in the milk and plasma of lactating women. J Nutr. 2017;147(7):1301–7.
Kanno C, Kobayashi H, Yamauchi K. Transfer of orally administered alpha-tocopherol into human milk. J Nutr Sci Vitaminol (Tokyo). 1989;35(6):649–53.
Bolisetty S, Gupta JM, Graham GG, Salonikas C, Naidoo D. Vitamin K in preterm breastmilk with maternal supplementation. Acta Paediatr. 1998;87(9):960–2.
Melo LR, Clemente HA, Bezerra DF, Dantas RC, Ramalho HM, Dimenstein R. Effect of maternal supplementation with vitamin E on the concentration of alpha-tocopherol in colostrum. J Pediatr. 2017;93(1):40–6.
Greer FR, Marshall SP, Foley AL, Suttie JW. Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatrics. 1997;99(1):88–92.
von Kries R, Shearer M, McCarthy PT, Haug M, Harzer G, Gobel U. Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother. Pediatr Res. 1987;22(5):513–7.
Canfield LM, Giuliano AR, Neilson EM, Blashil BM, Graver EJ, Yap HH. Kinetics of the response of milk and serum beta-carotene to daily beta-carotene supplementation in healthy, lactating women. Am J Clin Nutr. 1998;67(2):276–83.
Garcia L, Ribeiro K, Araujo K, Pires J, Azevedo G, Dimenstein R. Alpha-tocopherol concentration in the colostrum of nursing women supplemented with retinyl palmitate and alpha-tocopherol. J Hum Nutr Diet. 2010;23(5):529–34.
Sherry CL, Oliver JS, Renzi LM, Marriage BJ. Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids. J Nutr. 2014;144(8):1256–63.
Webb AL, Aboud S, Furtado J, Murrin C, Campos H, Fawzi WW, et al. Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids and tocopherols in HIV-infected Tanzanian women. Eur J Clin Nutr. 2009;63(3):332–9.
Chierici R, Saccomandi D, Vigi V. Dietary supplements for the lactating mother: influence on the trace element content of milk. Acta Paediatr Suppl. 1999;88(430):7–13.
Shaaban SY, El-Hodhod MAA, Nassar MF, Hegazy AE-T, El-Arab SE, Shaheen FM. Zinc status of lactating Egyptian mothers and their infants: effect of maternal zinc supplementation. Nutr Res. 2005;25(1):45–53.
Dodge ML, Wander RC, Butler JA, Du SH, Thomson CD, Whanger PD. Selenium supplementation increases the polyunsaturated fatty acid content of human breast milk. J Trace Elements Exper Med. 1998;12(1):37–44.
Dylewski ML, Picciano MF. Milk selenium content is enhanced by modest selenium supplementation in extended lactation. J Trace Elements Exper Med. 2002;15(4):191–9.
Flax VL, Bentley ME, Combs GF Jr, Chasela CS, Kayira D, Tegha G, et al. Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the breastfeeding, Antiretrovirals, and nutrition study. Am J Clin Nutr. 2014;99(4):950–6.
Moore M, Wandera R, Xia Y-M, Du S-H, Butler J, Whanger P. Selenium supplementation of Chinese women with habitually low selenium intake increases plasma selenium, plasma glutathione peroxidase activity, and milk selenium, but not milk glutathione peroxidase activity1. J Nutr Biochem. 2000;11(6):341–7.
Trafikowska U, Sobkowiak E, Butler JA, Whanger PD, Zachara BA. Organic and inorganic selenium supplementation to lactating mothers increase the blood and milk se concentrations and se intake by breast-fed infants. J Trace Elem Med Biol. 1998;12(2):77–85.
Trafikowska U, Zachara B, Wiacek M, Sobkowiak E, Czerwionka-Szaflarska M. Selenium supply and glutathione peroxidase activity in breastfed polish infants. Acta Paediatr. 1996;85(10):1143–5.
Holm C, Thomsen LL, Norgaard A, Markova V, Michaelsen KF, Langhoff-Roos J. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial. Acta Paediatr. 2017;106(2):256–60.
Yalcin SS, Baykan A, Yurdakok K, Yalcin S, Gucus AI. The factors that affect milk-to-serum ratio for iron during early lactation. J Pediatr Hematol Oncol. 2009;31(2):85–90.
Zapata CV, Donangelo CM, Trugo NMF. Effect of iron supplementation during lactation on human milk composition. J Nutr Biochem. 1994;5(7):331–7.
Breymann C, von Seefried B, Stahel M, Geisser P, Canclini C. Milk iron content in breast-feeding mothers after administration of intravenous iron sucrose complex. J Perinat Med. 2007;35(2):115–8.
Pires Medeiros JF, Ribeiro KD, Lima MS, das Neves RA, Lima AC, Dantas RC, et al. alpha-Tocopherol in breast milk of women with preterm delivery after a single postpartum oral dose of vitamin E. Br J Nutr. 2016;115(8):1424–30.
Thiele DK, Senti JL, Anderson CM. Maternal vitamin D supplementation to meet the needs of the breastfed infant: a systematic review. J Hum Lact. 2013;29(2):163–70.
Soares MM, Silva MA, Garcia PPC, Silva LSD, Costa GDD, Araújo RMA, et al. Efect of vitamin a suplementation: a systematic review. Ciência & Saúde Coletiva. 2019;24(3):827–38.
Shahrook S, Ota E, Hanada N, Sawada K, Mori R. Vitamin K supplementation during pregnancy for improving outcomes: a systematic review and meta-analysis. Sci Rep. 2018;8(1):11459.
Oliveira-Menegozzo JM, Bergamaschi DP, Middleton P, East CE. Vitamin A supplementation for postpartum women. Cochrane Database Syst Rev. 2010;(10):CD005944 1-CD. 48.
Tchum SK, Tanumihardjo SA, Newton S, de Benoist B, Owusu-Agyei S, Arthur FK, et al. Evaluation of vitamin a supplementation regimens in Ghanaian postpartum mothers with the use of the modified-relative-dose-response test. Am J Clin Nutr. 2006;84(6):1344–9.
Ruel MT, Dewey KG, MartInez C, Flores R, Brown KH. Validation of single daytime samples of human milk to estimate the 24-h concentration of lipids in urban Guatemalan mothers. Am J Clin Nutr. 1997;65(2):439–44.
Kelishadi R, Ataei E, Ardalan G, Nazemian M, Tajadini M, Heshmat R, et al. Relationship of serum magnesium and vitamin d levels in a nationally-representative sample of iranian adolescents: the CASPIAN-III study. Int J Prev Med. 2014;5(1):99–103.
Cheung MM, DeLuccia R, Ramadoss RK, Aljahdali A, Volpe SL, Shewokis PA, et al. Low dietary magnesium intake alters vitamin D-parathyroid hormone relationship in adults who are overweight or obese. Nutr Res. 2019;69:82–93.
Shams B, Afshari E, Tajadini M, Keikha M, Qorbani M, Heshmat R, et al. The relationship of serum vitamin D and Zinc in a nationally representative sample of Iranian children and adolescents: The CASPIAN-III study. Med J Islam Repub Iran. 2016;30(1):430.
Stuetz W, Carrara VI, McGready R, Lee SJ, Biesalski HK, Nosten FH. Thiamine diphosphate in whole blood, thiamine and thiamine monophosphate in breast-milk in a refugee population. PLoS One. 2012;7(6):e36280.
Stuetz W, Carrara VI, McGready R, Lee SJ, Erhardt JG, Breuer J, et al. Micronutrient status in lactating mothers before and after introduction of fortified flour: cross-sectional surveys in Maela refugee camp. Eur J Nutr. 2012;51(4):425–34.
Sakurai T, Furukawa M, Asoh M, Kanno T, Kojima T, Yonekubo A. Fat-soluble and water-soluble vitamin contents of breast milk from Japanese women. J Nutr Sci Vitaminol. 2005;51(4):239–47.
Lönnerdal B. Effects of maternal dietary intake on human milk composition. J Nutr. 1986;116(4):499–513.
Nail PA, Thomas MR, Eakin R. The effect of thiamin and riboflavin supplementation on the level of those vitamins in human breast milk and urine. Am J Clin Nutr. 1980;33(2):198–204.
Thomas MR, Sneed SM, Wei C, Nail PA, Wilson M, Sprinkle EE III. The effects of vitamin C, vitamin B6, vitamin B12, folic acid, riboflavin, and thiamin on the breast milk and maternal status of well-nourished women at 6 months postpartum. Am J Clin Nutr. 1980;33(10):2151–6.
Montalbetti N, Dalghi MG, Albrecht C, Hediger MA. Nutrient transport in the mammary gland: calcium, trace minerals and water soluble vitamins. J Mammary Gland Biol Neoplasia. 2014;19(1):73–90.
Ortega RM, Quintas ME, Andrés P, Martínez RM, López-Sobaler AM. Ascorbic acid levels in maternal milk: differences with respect to ascorbic acid status during the third trimester of pregnancy. Br J Nutr. 1998;79(5):431–7.
Lima MS, Dimenstein R, Ribeiro KD. Vitamin E concentration in human milk and associated factors: a literature review. J Pediatr (Versão em Português). 2014;90(5):440–8.
Medeiros JFP, da Silva Ribeiro KD, Lima MSR, das Neves RAM, Lima ACP, Dantas RCS, et al. α-tocopherol in breast milk of women with preterm delivery after a single postpartum oral dose of vitamin E. Br J Nutr. 2016;115(8):1424–30.
Boersma ER, Offringa PJ, Muskiet FA, Chase WM, Simmons IJ. Vitamin E, lipid fractions, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study. Am J Clin Nutr. 1991;53(5):1197–204.
Debier C. Vitamin E during pre-and postnatal periods. Vitam Horm. 2007;76:357–73.
Dimenstein R, Medeiros AC, Cunha LR, Araújo KF, Dantas JC, Macedo T, et al. Vitamin E in human serum and colostrum under fasting and postprandial conditions. J Pediatr. 2010;86(4):345–8.
Mardones P, Rigotti A. Cellular mechanisms of vitamin E uptake: relevance in α-tocopherol metabolism and potential implications for disease. J Nutr Biochem. 2004;15(5):252–60.
de Azeredo VB, Trugo NM. Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations. Nutrition. 2008;24(2):133–9.
Brion LP, Bell EF, Raghuveer TS. Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2003;(4):Cd003665.
Ostrea EM, Balun JE, Winkler R, Porter T. Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and β-carotene in the newborn infant. Am J Obstet Gynecol. 1986;154(5):1014–7.
Canfield L, Giuliano A, Neilson E, Yap H, Graver E, Cui H, et al. Beta-carotene in breast milk and serum is increased after a single beta-carotene dose. Am J Clin Nutr. 1997;66(1):52–61.
Rice AL, Stoltzfus RJ, de Francisco A, Chakraborty J, Kjolhede CL, Wahed M. Maternal vitamin a or β-carotene supplementation in lactating Bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency. J Nutr. 1999;129(2):356–65.
Khachik F, Spangler CJ, Smith JC, Canfield LM, Steck A, Pfander H. Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. Anal Chem. 1997;69(10):1873–81.
Berger VW. The (lack of) quality in assessing the quality of transplantation trials. Transpl Int. 2009;22(10):1029 author reply 3.
Berger VW. Is the Jadad score the proper evaluation of trials? J Rheumatol. 2006;33(8):1710–1 author reply 1-2.
Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Bouter LM, et al. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol. 1998;51(12):1235–41.
Pengel LH, Barcena L, Morris PJ. The quality of reporting of randomized controlled trials in solid organ transplantation. Transpl Int. 2009;22(4):377–84.
Acknowledgements
Not applicable.
Funding
There is no source of financial support.
Author information
Authors and Affiliations
Contributions
MK, RK and MB co-designed the study and survey materials, searching the databases. RSH and MK were involved in data collection and extracting the data. MK, RK, RSH and MB were responsible for conducting the review, interpretation and drafting the manuscript. MK, RK, RSH and MB revised the manuscript critically for important content. All authors approved the final manuscript to be submitted and published.
Corresponding authors
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors stated no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Keikha, M., Shayan-Moghadam, R., Bahreynian, M. et al. Nutritional supplements and mother’s milk composition: a systematic review of interventional studies. Int Breastfeed J 16, 1 (2021). https://doi.org/10.1186/s13006-020-00354-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13006-020-00354-0