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In the last few years, a variety of experimental and clinical studies concerning the formation, metabolism, and cellular effects of cholesterol oxidation products (COPs) have been carried out. Nevertheless, a substantial lack of knowledge exists regarding the possible intake of these compounds by the newborn through human and/or adapted formula mil...
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... g/100 mL) [13,14,16,17], cholesterol (7.33-13.96 mg/100 g) [18][19][20], retinol (29.88-83.07 μg/100 g) [20][21][22], and α-tocopherol (0.21-0.57 ...
... Regarding the cholesterol content, Scopesi et al. [18] reported that the mean cholesterol content in the mature HM was 12.02 mg/100 g, with a range of 6.5-18.4 mg/100 g, which is in accordance with our results (mean and median 13.97 and 13.78 mg/100 g; ranges 5.17-26.71 ...
This study aimed at investigating the different content of the selected macro- and micronutrients in human milk (HM) according to its fat content. We collected 34 HM samples from Korean mothers, and classified them into 3 groups according to their fat content. Then, their protein, lactose, cholesterol, retinol, tocopherol, and mineral contents were compared. When their contents were presented as per 100 g of HM, cholesterol, retinol, and tocopherol contents increased significantly from group A–C (p < 0.05), suggesting their positive correlation with the fat content. Alternatively, when these contents were considered as per normalized gram of HM fat content, no significant difference was observed between retinol and tocopherol contents in the three groups (p > 0.05), whereas cholesterol content was significantly lower in group C compared to A and B (p < 0.05). However, the fat content seemed to not affect the HM protein and lactose contents. Most minerals did not show statistical difference among three groups (p > 0.05). In addition, strong correlations among cholesterol, retinol, and tocopherol contents were observed, whereas these components were negatively correlated with lactose content to a small extent, and unrelated to protein content.
... Comparatively, we found total sterol concentrations of 6.46 ± 1.64 mg/100 mL of sample and 11.08 ± 2.11 mg/100 mL of IF liquid and powder, respectively. In contrast, cholesterol concentrations in IF may vary between 0.1 and 7.3 mg/g lipid (Scopesi et al., 2002). Our results range from 0.3 to 2.14 mg of cholesterol per g of lipid (Table S3, in Supplemental information). ...
... Little information has been reported for COPs and their metabolites in IF (Scopesi et al., 2002). 7α-hydroxycholesterol (7α-OH), 7βhydroxycholesterol (7β-OH), 7-ketocholesterol (7-keto), 5α,6α-epoxycholesterol (5,6α-epoxy), 5β,6β-epoxycholesterol (5,6β-epoxy), cholestane-3β,5α,6β-triol (triol), and 25-hydroxycholesterol (25-OH) (Gorassini, Verardo, Fregolent, & Bortolomeazzi, 2017) and 7-ketocholesterol are the most common COPs found in foods (Rodriguez-Estrada, Garcia-Llatas, & Lagarda, 2014). ...
... We cannot exclude that this discrepancy could be due to differences in the manufacturing process between Europe and the USA. 7keto was the third highest COPs in IF, with an average value of 1.42 μg/ scoop (0.77 μg/g lipids for PFI and 0.49 μg/g lipids for LIF); our results agree with Scopesi and coworkers (Scopesi et al., 2002) who found 0.3-11.2 µg/g of lipid of 7-keto from a set of ten IFs. ...
Approximately two-thirds of US infants receive infant formula (IF) as a primary or sole nutritional source during the first six months of life. IF is available in a variety of commercial presentations; from a manufacturing standpoint, they can be categorized as powder- (PIF) or liquid- (LIF) based formulations. Thirty commercial IFs were analyzed in their oxidative and non-oxidative lipid profiles. We identified 7-ketocholesterol – a major end-product of cholesterol oxidation – as a potential biomarker of IF manufacturing. The statistical analysis allowed a re-classification of IF based on their metabolomic fingerprint, resulting in three groups assigned with low-to-high oxidative status. Finally, we modeled the dietary intake of cholesterol, sterols, and 7-ketocholesterol in the first year of life. The database provided in this study will be instrumental for scientists interested in infant nutrition, to establish bases for epidemiological studies aimed to find connections between nutrition and diet-associated diseases, such as sitosterolemia.
... Comparatively, we found total sterol concentrations of 6.46 ± 1.64 mg/100 mL of sample and 11.08 ± 2.11 mg/100 mL of IF liquid and powder, respectively. In contrast, cholesterol concentrations in IF may vary between 0.1 to 7.3 mg/g lipid (Scopesi et al., 2002;Zunin, Calcagno, & Evangelisti, 1998). Our results range from 0.3 to 2.14 mg of cholesterol per g of lipid (Table S3, Supplemental information). ...
... Overall, PIF contained higher amounts of tocopherol compared to LIF (p < 0.05, Table 1), with the γ-tocopherol being 5-fold higher in powder formulations. These results agree with Lee et al. (Lee, Jang, & Kim, 2013) and Miquel et al (Miquel et al., 2004) (Scopesi et al., 2002). 7α-hydroxycholesterol (7α-OH), 7β-hydroxycholesterol (7β-OH), 7-ketocholesterol (7-keto), 5α,6α-epoxycholesterol (5,6α-epoxy), 5β,6β-. ...
... We cannot exclude that this discrepancy could be due to differences in the manufacturing process between Europe and the USA (Guo, 2014). 7-keto was the third highest COPs in IF, with an average value of 1.42 μg/scoop (0.77g/g lipids for PFI and 0.49 g/g lipids for LIF); our results agree with Scopessi and coworkers (Scopesi et al., 2002) who found 0.3 -11.2 µg/g of lipid of 7-keto from a set of ten IFs . Conversely, our data is lower than that reported by others (1.2 -11.2 µg/g of lipids), in a study performed on six . ...
Approximately two-thirds of US infants receive infant formula (IF) as a primary or sole nutritional source during the first six months of life. IF is available in a variety of commercial presentations, although from a manufacturing standpoint, they can be categorized in powder-(PIF) or liquid-(LIF) based formulations. Herein, thirty commercial IFs were analyzed in their oxidative and non-oxidative lipidomics profiles. Results show that LIFs have a characteristic lipidomic fingerprint, enriched in an oxidated form of cholesterol, and a lower load of phytosterols. We identified 7-ketocholesterol-a major end-product of cholesterol oxidation-as a potential biomarker of IF manufacturing. Our data allowed re-classification of IF based on their metabolomic fingerprint, resulting in three groups assigned with low-to-high oxidative status. Finally, we modeled the dietary intake for cholesterol, sterols, and 7-ketocholesterol in the first year of life. The database provided in this study will be instrumental for scientists interested in infant nutrition, to establish bases for epidemiological studies aimed to find connections between nutrition and diet-associated diseases, such as sitosterolemia.
... The cholesterol in BM is prone to auto-oxidation, resulting into the formation of several cholesterol oxidation products, also known as oxysterols, containing an additional hydroxyl, ketone or epoxide group on the sterol nucleus [7]. These compounds have received much attention due to their potential toxicity, and hence 7-ketocholesterol (7KC), is currently used as a biomarker of cholesterol oxidation in milk subjected to industrial processes or storage procedures [8]. However, cholesterol auto-oxidation and the formation of oxysterols in fresh BM is very low due to the low oxygen concentration [7]. ...
... The concentrations of 7KC (18 μg/L in C; 13 μg/L in TM; 10 μg/L in MM) were relatively low and consistent with previous findings [8].We could observe a progressive reduction of 7KC from C to MM (P = 0.018). Neither difference nor significant trend were observed for 7βOHC (see Table 2 and Fig. 1). ...
... Today nearly 60% of infants are never breastfed (95,96) and childhood obesity may have its origins, at least in part, in insufficient breastfeeding (6)(7)(8)97). Components of the manufactured infant formula might also be responsible for the negative metabolic impact of the absence of breastfeeding (98). Moreover, certain miRNA species enriched in cow milk -the main component of infant formula -inhibit BeAT development (99). ...
Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.
... 12 Despite the abovementioned difference between our cholesterol content in colostrum and those in the literature, in mature HM our contents of total animal sterols and total sterols (which ranged from 11 to 24 mg per 100 mL in both cases) were consistent with the data found in the literature (11-20 mg per 100 mL and 12-26 mg per 100 mL of HM, respectively). [9][10][11]33,35,37,38 Moreover, our cholesterol and desmosterol contents (11-22 mg per 100 mL and 0.3-2.3 mg per 100 mL, respectively), as well as the lathosterol contents (25-70 µg per 100 mL), were also consistent with the data found in the literature (2-32 mg per 100 mL, 0.8-2.1 mg per 100 mL and 44-80 µg per 100 mL, respectively). ...
... Furthermore, focusing only on the coastal areas of different countries, similar cholesterol contents (mg per 100 mL) have been reported: 15.5 in 1 month HM 11 and 15.7 in 2 month HM from Finland; 10 12.8 in 1 to 3 month HM from the Netherlands; 43 and 12.0 in mature HM from Italy. 38 The same tendency was observed in the present study: the contents of total, animal and plant sterols from the coastal area in Spain (Valencia-Murcia) were statistically significantly higher than those from the central area (Madrid) ( p < 0.05), and desmosterol was the main sterol responsible for this difference (as it represented 9% of total sterols for the coastal area and 4% for the central area). ...
Human milk (HM) is the exclusive food during the first 4-6 months of the infant’s life. Breastfeeding has been related to an important health benefits for infants, so it is important to study also its bioactive compounds as sterols. Cholesterol (main sterol) has an important role as structural component of cells, in the formation of new tissues and as precursor of vitamin D, hormones and bile acids. In this study, for the first time, the sterol (cholesterol, desmosterol, lathosterol, lanosterol, campesterol, stigmasterol and β-sitosterol) contents in 10 pools of colostrum, transition, 1, 3 and 6 month HM obtained from Spanish volunteers from two different geographical areas (coastal and central) were quantified by gas chromatography. Moreover, sterol intake and their bioaccessibility (BA) were also estimated in order to know the fate of sterols after digestion. The total sterol content decreased to the half throughout lactation, ranging from 24 to 11 mg/100 mL. Furthermore, animal sterol intake was from 200 to 400 times higher than plant sterol intake. The BA of total sterols ranged from 45 to 69%, being higher in the first month coinciding with the highest milk fat content. In conclusion, sterol content varies depending on the lactation stage and the geographical area, and their BA can be positively impacted by higher lipid content. All these data may contribute to develop infant formulas more similar to HM in terms of composition and behaviour after digestion according to the lactation stage involved.
... Exposure to food-derived toxic compounds can be critical in sensitive populations, specially infants and children. Powdered milk is a known source of COPs, although the reported amounts differ according to the milk process (Dionisi et al., 1998;Leonarduzzi et al., 2005;Przygonski et al., 2000;Romeu-Nadal et al., 2007;Scopesi et al., 2002;Pickett-Bernard, 2006). Powdered milk is manufactured using the wet blending-spray drying process in cow milk. ...
... This process provides the proper conditions for triggering hydroperoxide formation that lead lipid and protein oxidation, among others reactions (Damjanovic Desic and Birlouez-Aragon, 2011; Sieber, 2005). McCluskey and co-workers found up to 60 ppm COPs in skim powdered milk (McCluskey and Devery, 1993), whereas Scopesi et al. (2002) demonstrated that the content in 7-keto is in baby formula is 5-fold higher than human breast milk. Infant formula plays an important role in infant growth and health; according to a report from the US Institute of Medicine, it may be the only source of nutrition for many infants during the first 4-6 months of life (2006). ...
Food consumption can lead to the accumulation of certain chemical compounds able to exert toxic activities against humans. Of mayor interests are those molecules generated during food processing and handling, since their occurrence and distribution depend of many intrinsic and extrinsic factors. Cholesterol – a lipid constituent of mammalian cells – is the precursor of several toxic molecules known as cholesterol oxidation products (COPs). In the last decades, it has been demonstrated that food processing can dramatically trigger COPs accumulation in meats, eggs, dairy products, fish and poultry. On the other hand, countless scientific evidences have pointed out the highly toxic and pathogenic activities of COPs, from cancer stimulation to neurodegenerative disorders, via molecular mechanisms that are largely unexplored. The aim of this review is to merge the evidence on COPs accumulation in foods and their toxic activities through dietary intake, as from in vivo and in vitro studies. We consider that is imperative to systematically monitor the formation of COPs and bridge these quantitative efforts with risk exposure assessment on sensitive populations.
... Ранее было показано, что концентрация ХС в женском молоке ниже, чем в нативном коровьем [28] и выше, чем в стандартной детской смеси [29,30]. Средний уровень ХС в женском молоке подвержен значительным индивидуальным колебаниям и зависит как от степени зрелости молока, так и от методов его измерения [31][32][33][34][35][36][37]. Длительность, трудоемкость и многостадийность методик приготовления образцов для такого рода анализов также может вносить дополнительные отклонения и погрешности в полученные результаты. ...
Objective. Comparison of sterols in samples of human milk and infant formulas for bottle-feeding.
Materials and methods. The work used samples of mature breast milk of women from the Moscow region, and also 4 infant formulas available in the Russian market and differing in their lipid component. In formula No 1, based on whole goat’s milk, it was represented by dairy fat and vegetable oil (50:50); in goat’s (No 2) and cow’s (No 3) milk formulas and in an extensively hydrolysed cow’s milk casein-based formula (No 4) the lipid component was represented mainly by various vegetable oils. The quantitative and qualitative analysis of sterols in the studied samples was performed by gas chromatography-mass spectrometry.
Results. The maximal amounts of cholesterol were found in human milk, where its levels varied in the range 2.3–2.5 mg/g fat, cholesterol being the only sterol found in breast milk. Total cholesterol counts in infant formulas differed significantly (mg/g fat): formula No 1 – 1.4 ± 0.04; formula No 2 – 1.1 ± 0.03; formula No 3 – 0.6 ± 0.04; formula No 4 – 0.03 ± 0.002. Also, the presence of phytosterols were found in the formulas: brassicasterol, campesterol, stigmasterol, sitosterol, 5-avenasterol, amyrin, 7-sitosterol. The main individual phytosterols in all kinds of infant formulas were β-sitosterol and campesterol detectable in the range from 0.5 to 1.5 mg/g fat. The studied samples demonstrated a distinct differentiation of sterol composition, including
cholesterol, depending on the type of the formula, their lipid component and manufacturing technology. A formula, where the lipid component was represented by dairy fat and vegetable oils, was characterised by an approximately equal cholesterol-phytosterol ratio (46% vs. 54%, respectively), and their cholesterol content was the closest to human milk.
Conclusion. Preservation of native dairy fat in an infant formula approximates its lipid composition to human milk, in particular, as regards cholesterol levels.
Key words: gas chromatography–mass spectrography, human milk, infant formulas for formula feeding, phytosterols, cholesterol
... mg/L and squalene: 3.90-4.90 mg/L (Mellies et al., 1979;Clark et al., 1983;Kallio et al., 1989;Huisman et al. 1996;Scopesi et al. 2002;Laitinen et al., 2009;Ramalho et al., 2011;Kamelska et al., 2013;Alvarez-Sala et al., 2015)) and is more abundant than in IFs. ...
... In the few studies available on the profile of sterols in IF, the most abundant were found to be b-sitosterol (11-83 mg/L) and cholesterol (3-258 mg/L), followed by campesterol (7-32 mg/L), stigmasterol (3-12 mg/L), desmosterol (2.4-4.3 mg/L), brassicasterol (1-3 mg/L) and sitostanol (0.3-1.4 mg/L) (Huisman et al. 1996;Zunin et al. 1998;Scopesi et al. 2002;Maduko & Park 2007;Kamelska et al. 2011;Ramalho et al. 2011;Claumarchirant et al. 2015). ...
... The cholesterol concentrations found in our study were comparable to those reported by other authors (3-258 mg/L; 3.0-8.9 mg/100 g reconstituted IF) in bovine milk-based IFs (Huisman et al. 1996;Zunin et al. 1998;Scopesi et al. 2002;Kamelska et al. 2011;Ramalho et al. 2011;Ahn et al. 2012;Jeong et al. 2012;Claumarchirant et al. 2015) and lower than those found in caprine milk-based IFs (9.7-9.9 mg/100 g reconstituted IF) (Maduko & Park 2007) and in mature HM (46-283 mg/L) (Mellies et al. 1979;Clark et al. 1983;Kallio et al. 1989;Huisman et al. 1996;Scopesi et al. 2002;Laitinen et al. 2009;Ramalho et al. 2011;Kamelska et al. 2013;Alvarez-Sala et al. 2015). In this regard, breastfed infants have significant higher total cholesterol and LDL-cholesterol than infants fed with infant formulas (Kallio et al. 1992;Wong et al. 1993) or mixed fed (HM and IFs) (Harit et al. 2008). ...
Sterols are components present in the fat fraction of infant formulas (IFs). Their characterization is therefore of interest, though there are no official reference methods for their analysis in these matrices.
Aim: To validate a gas chromatographic method with flame ionization detection for the determination of animal (cholesterol and desmosterol) and plant sterols (brassicasterol, campesterol, stigmasterol, β-sitosterol and sitostanol) found in IFs.
All correlation coefficients obtained for the calibration curves of sterols studied were >0.99. Limits of detection (<1 μg/100 mL) and quantification (<4 μg/100 mL) are suitable for sterols determination in IFs. The within-assay precision ranged from 1.6% to 8.8%, while the between-assay precision was <10% for most of sterols. Accuracy was satisfactory and was calculated by recovery assays (ranging 93–108%). The analytical parameters obtained showed the suitability of the proposed method for the determination of sterols in IFs.
... mg/L and squalene: 3.90-4.90 mg/L (Mellies et al., 1979;Clark et al., 1983;Kallio et al., 1989;Huisman et al. 1996;Scopesi et al. 2002;Laitinen et al., 2009;Ramalho et al., 2011;Kamelska et al., 2013;Alvarez-Sala et al., 2015)) and is more abundant than in IFs. ...
... In the few studies available on the profile of sterols in IF, the most abundant were found to be b-sitosterol (11-83 mg/L) and cholesterol (3-258 mg/L), followed by campesterol (7-32 mg/L), stigmasterol (3-12 mg/L), desmosterol (2.4-4.3 mg/L), brassicasterol (1-3 mg/L) and sitostanol (0.3-1.4 mg/L) (Huisman et al. 1996;Zunin et al. 1998;Scopesi et al. 2002;Maduko & Park 2007;Kamelska et al. 2011;Ramalho et al. 2011;Claumarchirant et al. 2015). ...
... The cholesterol concentrations found in our study were comparable to those reported by other authors (3-258 mg/L; 3.0-8.9 mg/100 g reconstituted IF) in bovine milk-based IFs (Huisman et al. 1996;Zunin et al. 1998;Scopesi et al. 2002;Kamelska et al. 2011;Ramalho et al. 2011;Ahn et al. 2012;Jeong et al. 2012;Claumarchirant et al. 2015) and lower than those found in caprine milk-based IFs (9.7-9.9 mg/100 g reconstituted IF) (Maduko & Park 2007) and in mature HM (46-283 mg/L) (Mellies et al. 1979;Clark et al. 1983;Kallio et al. 1989;Huisman et al. 1996;Scopesi et al. 2002;Laitinen et al. 2009;Ramalho et al. 2011;Kamelska et al. 2013;Alvarez-Sala et al. 2015). In this regard, breastfed infants have significant higher total cholesterol and LDL-cholesterol than infants fed with infant formulas (Kallio et al. 1992;Wong et al. 1993) or mixed fed (HM and IFs) (Harit et al. 2008). ...
Aim:
To validate a gas chromatographic method with flame ionization detection for the determination of animal (cholesterol and desmosterol) and plant sterols (brassicasterol, campesterol, stigmasterol, β-sitosterol and sitostanol) found in IFs. All correlation coefficients obtained for the calibration curves of sterols studied were >0.99. Limits of detection (<1 μg/100 mL) and quantification (<4 μg/100 mL) are suitable for sterols determination in IFs. The within-assay precision ranged from 1.6% to 8.8%, while the between-assay precision was <10% for most of sterols. Accuracy was satisfactory and was calculated by recovery assays (ranging 93-108%). The analytical parameters obtained showed the suitability of the proposed method for the determination of sterols in IFs.
