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Why was this study done?
Faced with the increasing prevalence of obesity in women, researchers have investigated possible alterations and effects of melatonin and cortisol in colostrum and human milk resulting from pregnancy affected by maternal obesity. Understanding these effects can guide strategies for addressing obesity and promoting breastfeeding. However, there is a lack of information in the scientific literature regarding cortisol levels in the colostrum of obese women and the mechanisms through which this hormone acts on cellular components derived from colostrum or breast milk in pregnancies impacted by obesity.
What did the researchers do and find?
The impact of maternal obesity on the levels and actions of melatonin and cortisol in colostrum and breast milk was analyzed based on results published in scientific literature. For this review, scientific articles were extracted from databases such as PubMed, Medline, Lilacs, and Scopus on February 17, 2023, using the keywords: Obesity, Colostrum, Breast Milk, Melatonin, and Cortisol. The conclusions drawn are based on 5 scientific articles that were identified, screened, and deemed eligible for inclusion. Regarding melatonin, it was observed that obese mothers have high levels of this hormone in their colostrum, and specifically for this group, there is a potential for restoring the functional activity of colostrum phagocytes and increasing lymphocyte proliferation. On the other hand, maternal obesity or body mass index does not appear to alter cortisol levels in breast milk.
What do these findings mean?
This review demonstrates that melatonin is present in higher concentrations in the colostrum of obese women and has the potential to restore the functional activity of colostrum phagocytes to a level similar to that of the eutrophic group, while also increasing the lymphocyte proliferation index. Additionally, maternal obesity does not seem to influence cortisol concentrations in human milk. However, due to the limited number of studies on melatonin and cortisol in human colostrum from pregnant women with obesity, the need for more experimental and observational research on these respective hormones in human milk expressed during the first days after birth is emphasized.
Highlights
There is an indication that melatonin is elevated in the colostrum of obese women, and specifically for this group, it has the potential to restore the functional activity of colostrum phagocytes and increase the proliferation of lymphocytes.
Melatonin is found in higher concentrations in the colostrum of obese women and has the potential to restore the functional activity of colostrum phagocytes to a level similar to that of the eutrophic group. Additionally, it increases the rate of lymphocyte proliferation.
Maternal obesity did not influence cortisol concentrations in human milk.
In a study included in this review, which aimed to determine the influence of maternal and infant biological and sociodemographic factors on the levels of glucocorticoid hormones in human milk, the authors reported that although cortisol levels were similar in the milk of the eutrophic group and overweight and obese women, cortisone levels were significantly higher in normal weight women. Furthermore, there was a strong positive correlation between cortisone and cortisol levels in human milk.
Understanding the changes and effects of melatonin and cortisol in colostrum and human milk caused by obesity can provide knowledge that will serve as guidelines for the development of new biotechnologies mimicking the mechanisms of maternal and child protection. These strategies can be used to address obesity itself and strengthen breastfeeding.
INTRODUCTION
Obesity is a significant public health issue that affects countries across various income levels, including high, middle, and low-income nations, and its prevalence continues to increase globally. As a chronic and inflammatory disease, it has wide-ranging repercussions on the overall health balance, necessitating interventions by healthcare professionals to mitigate its detrimental effects on the body and improve the population’s quality of life.
According to the World Health Organization (2023), obesity has reached epidemic proportions. Globally, more than 1 billion individuals are classified as obese, including 650 million adults, 340 million adolescents, and 39 million children. This widespread issue affects populations in high, middle, and low-income countries alike1.
It is well-established that being overweight or obese increases the risk of developing numerous diseases. Some of the conditions associated with excess weight include asthma, musculoskeletal disorders, sleep disorders, type 2 diabetes mellitus, liver and kidney dysfunction, cardiovascular disease, infertility, and various types of cancer. The types of cancer linked to overweight and obesity include breast, endometrial, gallbladder, ovarian, prostate, kidney, liver, and colon cancer1-4. Additionally, it has been observed that individuals who are obese are three times more likely to be hospitalized in the case of COVID-191.
It is a complex problem to resolve due to the broad etiology of excess weight that involves genetic, physiological, cultural, political, socioeconomic5,6 and environmental factors, such as temperature7, rainfall8 and luminosity9.
Obesity is preventable and the key to prevention is to act early, even before the baby is conceived. Adequate nutrition during pregnancy and breastfeeding represent important actions to reduce obesity1. Breastfeeding for a duration of 6 months or more, even in the presence of maternal obesity, helps reduce the risk of childhood overweight in the offspring10. Therefore, the promotion of breastfeeding should be incorporated into public health initiatives aimed at mitigating the consequences of obesity1,10.
Pregnancy affected by obesity or its consequences in the pregnant woman and the offspring leads to alterations in the biochemical, immunological, and hormonal components of colostrum11-13 and in hormonal levels, including melatonin.
The melatonin hormone is primarily produced by the pineal gland and plays a crucial role in regulating circadian rhythms. It also has physiological functions related to the maintenance of energy homeostasis and is involved in the pathophysiological mechanisms associated with the development and persistence of obesity and metabolic syndrome. Furthermore, melatonin can influence the secretion of adipokines, which are signaling molecules produced by adipose tissue14-17.
In addition, colostrum contains an active component of the hormone melatonin. When newborns receive colostrum through breastfeeding, this hormone plays a significant role in synchronizing the biological rhythms between the mother and child. Moreover, melatonin enhances the activity of colostrum phagocytes, thereby bolstering its ability to protect the newborn against pathogens that can cause infections18-20.
In the colostrum of obese women, melatonin is found in higher concentrations compared to colostrum from eutrophic women. This increase in melatonin levels has a direct impact on the infant by enhancing the protective activity of phagocytes. This effect is recognized as a potential maternal-infant protection mechanism against obesity13. Therefore, maternal melatonin appears to contribute to the development of the offspring’s circadian rhythm and provides protective effects against various human conditions, including obesity and metabolic dysregulation21.
Melatonin, therefore, is an important hormone present in colostrum. However, it exhibits fluctuations throughout the day in accordance with the circadian rhythm (light/dark cycle) and is influenced by abiotic factors. It is worth noting that this abiotic influence is not limited to melatonin alone. There is metabolic and physiological evidence indicating that other hormones are also closely associated with sleep and circadian rhythms, including cortisol22.
Cortisol is the primary circulating glucocorticoid hormone, produced by the hypothalamic-pituitary-adrenal axis, which is one of the main neuroendocrine systems associated with the stress response. In its chronic form, when combined with positive energy balance (positive feedback), cortisol contributes to an increased risk of obesity23.
Elevated cortisol levels are associated with obesity24,25; however, obese individuals may also have normal levels of this hormone26, 27.
For the child, cortisol is essential for the development of biological rhythms. After birth, during lactation, cortisol can be transferred to the infant via breastfeeding, providing synchronization between day and night periods28.
Cortisol is also involved in inflammatory processes in colostrum cells and contributes significantly to the immune response29. Thus, the passive transfer of cortisol helps in immunological protection via breastfeeding in the presence of microorganism, through its ability to modulate the functional activity of colostrum phagocytes30.
It is possible that melatonin and cortisol present in colostrum and breast milk represent a mother-infant protection mechanism against both the development of obesity and infections in infants. Therefore, understanding the changes and effects of melatonin and cortisol in colostrum and human milk during pregnancy, influenced by obesity, can provide valuable knowledge for developing new biotechnologies that mimic the protective mechanisms between mother and infant. These findings can also be used as strategies for addressing obesity itself and strengthening breastfeeding practices.
The objective of this study is to analyze the impact of maternal obesity on the levels and functions of melatonin and cortisol in colostrum and breast milk.
METHODS
This is a systematized review type study, based on the protocol framework of the “Preferred Reporting Items for Systematic Reviews and Meta Analyzes” (PRISMA)31, but it is not characterized as a systematic review because it does not exhaust all indexing databases of journals. when selecting articles.
The PICO strategy (Patient, Intervention, Comparison and “Outcomes” - outcome) was used, and the initials of the pure acronym were defined as follows:
- P: obese women, I: measurements of hormone levels or the action of the hormones cortisol and melatonin in colostrum or breast milk, C: colostrum or breast milk of eutrophic women and O: relation of maternal obesity to levels of cortisol or melatonin or under the action of these hormones on cell components of colostrum from obese women.
Therefore, this study included original scientific articles that were available in full and published in English up until January 31, 2023. These articles were selected based on their relevance to the proposed theme, while literature review articles and duplicates found in the databases or in different languages were excluded from the analysis.
A systematic literature search was conducted in online databases, including PubMed, Medline, Lilacs, and Scopus, on February 17, 2023. The search utilized the following descriptors and Boolean operators: “Obesity AND Cortisol AND Colostrum,” “Obesity AND Cortisol AND Breast Milk,” “Obesity AND Melatonin AND Colostrum,” and “Obesity AND Melatonin AND Breast Milk.”
Initially, duplicate articles were identified and excluded using the Zotero program. Following this step, a screening process was performed by reviewing the titles of the articles. Any papers that were deemed unrelated to the topic were excluded. Subsequently, the abstracts of the selected articles were reviewed, and a detailed reading of the full articles was conducted. Articles that did not meet the predetermined inclusion and exclusion criteria were excluded from this review (figure 1).
RESULTS
37 articles were identified in the PubMed, Medline, Lilacs, and Scopus databases. Among these, 15 articles were excluded as duplicates. After applying the inclusion and exclusion criteria, a total of 5 articles were included in this review. Two articles focused on melatonin, and three studies analyzed cortisol, as shown in Figure 1.
The included articles are described in Table 1. One study investigated melatonin levels in the colostrum of obese women, while two studies examined the effects of melatonin on colostrum cells in obese women.
Table 1 : Studies included in the review, distributed according to author and date, objective, type of study, sample used and outcomes.
Regarding cortisol, three studies reported that cortisol levels did not differ in the colostrum of obese women. However, no studies evaluated the effects of cortisol on the cellular components of colostrum or breast milk in the context of maternal obesity (Table 1).
DISCUSSION
The literature review yielded results indicating that melatonin levels are elevated in the colostrum of obese women. This increase in melatonin has the potential to restore the functional activity of colostrum phagocytes and enhance lymphocyte proliferation, particularly in this group. However, regarding cortisol, it has been observed that body mass index or maternal obesity do not affect the levels of this hormone in breast milk. There is a dearth of information in the scientific literature regarding cortisol levels in the colostrum of obese women and the mechanisms by which this hormone acts on the cellular components derived from colostrum or breast milk in women with pregnancies affected by obesity.
Melatonin and maternal obesity
Data on maternal obesity and melatonin in colostrum or human milk are limited in the scientific literature. Only one study from Brazil described melatonin levels in the colostrum of obese women, showing higher levels in the obese group compared to the eutrophic group during daytime collection13.
It is important to note that melatonin levels in colostrum may differ from those in blood, as other studies have reported reduced serum melatonin levels in the presence of obesity16,36,37. Additionally, studies have shown that restoring melatonin levels can have beneficial effects on lipid profiles, hepatic lipid accumulation, and obesity38-43.
The higher melatonin levels observed in colostrum of obese women may represent a beneficial mechanism for promoting protective effects against obesity in infants. However, further studies are needed to explore this topic, as the current research has limitations. The analyzed sample was specific to a particular region, and only daytime colostrum samples were considered, without considering possible circadian disruptions associated with obesity.
Melatonin has also shown an important immunomodulatory role for colostrum mononuclear cells, which are crucial for infant protection against infections and immune response, including phagocytes13 and lymphocytes32. It is known that in the colostrum of obese women, mononuclear phagocytes may exhibit reduced functional activity13, and levels of T lymphocytes, CD4+ T lymphocytes, and the proliferation index of total lymphocytes are also diminished32.
It is essential to emphasize that the alterations observed in cells do not necessarily imply a decrease in the protective potential of colostrum from obese women. In its natural state, these cells are immersed in an environment containing numerous modulating bioactives, including melatonin13. Melatonin in colostrum mononuclear phagocytes from obese women has the potential to restore cell activity to a level similar to that seen in colostrum from eutrophic women13. In lymphocytes, melatonin, as well as important adipokines such as leptin and adiponectin, modulate the behavior of colostrum lymphocytes, increasing their proliferation rate and affecting intracellular calcium levels and apoptosis rates32.
Understanding the variations in melatonin levels and its actions in human colostrum is crucial for comprehending the biological mechanisms underlying colostrum’s protective effects against the consequences of pregnancy impacted by maternal obesity, ultimately benefiting the infant. This knowledge, which holds potential for clinical application, highlights melatonin as a promising target for interventions aimed at controlling body weight and metabolic diseases associated with obesity.
Cortisol and maternal obesity
The results of the studies included in this review that analyzed cortisol levels indicated that maternal excess weight was not a determining factor for altering cortisol levels in breast milk33-35. However, in blood studies, some indicate high cortisol levels in obese individuals24, 25, while others describe normal levels26, 27.
The limited number of studies on the subject contributes to the differences found in each study. Additionally, studies use different assessment methods for cortisol. Isolating serum cortisol levels as a marker is inadequate as it does not represent the actual hormone level available to the cells, nor does it consider its physiological fluctuations, including circadian variations and stress response variations (acute or chronic)44.
In one of the included studies, which aimed to determine the influence of maternal and infant factors on glucocorticoid hormone levels in human milk, the authors reported that although cortisol levels were similar in the milk of eutrophic, overweight, and obese women, cortisone levels were significantly higher in normal-weight women. Furthermore, there was a strong positive correlation between cortisone and cortisol levels in human milk35.
It is important to note that cortisol is converted to cortisone by enzymes such as the 11β-HSD2 enzyme, which transforms active cortisol into inactive cortisone. These enzymes are potential targets for the treatment of obesity and metabolic syndrome27,45,46.
Cortisol can be absorbed from the gastrointestinal tract and affect organ development as well as postnatal adaptation through circulation. It plays an important role in child development33.
Exposure to cortisol in breast milk has been associated with a lower absolute body mass index percentile at 2 years of age and may protect female infants against rapid increases in body mass index, suggesting that early exposure to the hormone may provide protection against later obesity and indicate taller and thinner phenotypes47. This highlights the importance of cortisol for infant development.
Another relevant finding in the literature is that cortisol concentrations may not change as a result of milk pasteurization33, but premature births contribute to elevated cortisol levels33,34. Other important factors that influence cortisol levels include the time of day and the stages of milk maturation (colostrum, transitional milk, or mature milk)28.
However, it is important to acknowledge the limitations of the studies included in this review, as they do not consider the influence of maternal obesity and cortisol on the different stages of milk maturation and chronobiology. Nevertheless, they provide relevant results that help fill gaps in the scientific literature.
Study limitation
This study has a limitation in terms of the small number of included studies (n=5). All the studies included in the review provided samples that were representative of specific regional populations from different locations. However, they did not take into account the influence of chronobiology, such as the time of day when the milk collection was performed, or the different stages of milk maturation. This limitation makes it difficult to generalize the data. Nonetheless, despite this limitation, the topic addressed in the study is current, has potential for clinical application, and is highly relevant to the scientific literature.
CONCLUSION
Melatonin is present in higher concentrations in the colostrum of obese women and has the potential to restore the functional activity of colostrum phagocytes to a level similar to that of the eutrophic group. It also increases the rate of lymphocyte proliferation.
Maternal obesity does not have an influence on cortisol concentrations in human milk.
