Fig 4 - uploaded by Kenji Ohyama
Content may be subject to copyright.
Changes in mean urine excretion volume of (a) estrone, (b) estriol, (c) estradiol and (d) pregnanediol after intake of cow milk in prepubertal children (mean 1 SE, n = 6).
Source publication
Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregna...
Context in source publication
Context 1
... in urinary excretion volumes of E1, E2, E3 and preg- nanediol are shown in Figure 4. Urinary excretion patterns were similar among these four hormones. Peak excretion volume of Fig. 1 Comparison between basal levels and peak levels of (a) serum estrone (E1), (b) estradiol (E2) and (c) progesterone before and after intake of cow milk in men (n = 7). Fig. 2 Comparison between basal and nadir levels of (a) serum luteinizing hormone, (b) follicle-stimulating hormone and (c) test- osterone before and after intake of cow milk in men (n = ...
Citations
... Heat treatment (70 °C and 95 °C) does not affect E1 and E2 concentrations compared to unprocessed raw milk [168]. The concentration of E1 sulfate increases from 30 pg/mL in non-pregnant cows up to 151 pg/mL in pregnant cows at 40-60 days of gestation, and to a maximum level of 1000 pg/mL in cows at 220 days of gestation [169]. Farlow et al. [170] compared the estrogen concentrations of commercial cow's and goat's milk. ...
... As the milk of pregnant dairy cows is pooled, commercial cow's milk contains higher estrogen amounts compared to former times, when lactation of cows was synchronized and cows gave birth only in spring time. Maruyama et al. [169] analyzed the exposure to exogenous estrogen through the intake of commercial milk produced from pregnant cows in children and adults. Urine concentrations of E1, E2, E3, and pregnanediol significantly increased in all adults and children after intake of 600 mL/m 2 of commercial cow's milk. ...
... The net increase in E2 excretion from the basal E2 levels in urine (before the intake) was 39-109 ng/4 h in this study. These data indicate that the intake of estrogens from cow's milk corresponds to the daily estrogen production rate in prepubertal boys [169]. Of note, not only milk but all dairy products, especially milk fat, contains estrogens that enhance the dietary estrogen exposure derived from cow's milk and dairy products [174,175]. ...
Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.
... [14] Many studies have confirmed that dairy food (ghee, milk, yogurt, buttermilk etc) consumption plays a role in influencing women's reproductive health, especially in conditions that involve hormonal deregulation. [15] Some studies have identified associations between intakes of total dairy foods and a decreased risk of endometriosis. [16] In addition, a reduced risk of uterine leiomyomata was associated with increasing dairy food intake. ...
Ayurveda recognizes menstruation as a physiological and self-purifying process; it is also governed by the actions of the Doshas. Ayurveda has prescribed a mode of life to be adopted by menstruating women - a series of Do’s and Don’ts - called as Rajaswala Paricharya, which aims to protect the health of the menstruating woman and prevent any health defects in the child, in case any conception happens. Menstrual Dysfunctions Risk Factors are conventionally divided into social and medico-biological. Unfortunately, it has been observed that the Rajaswala Paricharya is neither being publicized nor followed by the women in modern era. Also, the wrong information spread by media and manufacturers of sanitary napkins. WHO, UNICEF, NHM-GOI all are emphasizing on improving the reproductive health of adolescent girls and supports the accessible WASH facilities. But, they do not emphasize certain do’s and don'ts during menstrual days. So, Ayurveda physician has to promote this Paricharya for enhancement of reproductive health of female. With little effort, women naturally increased observance of the restrictions as they practiced them and experienced the benefits. Aim of this is to avoid vitiation of Vata, Pitta and Kapha, prevent formation of Ama and restore the Bala and nurture the Agni of the female. Thus, developing a correct and a positive outlook towards menstruation i.e., Rajaswala Paricharya is as important as practicing them. Girls may be benefited from it by responding appropriately to physical and psychological changes that occur during menstruation as well as by experiencing fewer symptoms.
... In the study of Maruyama et al. [31] men, women and children were given 600 mL of milk from cows known to be at an advanced stage of pregnancy, and urine and blood samples were obtained at 15, 30, 45, 60, 90 and 120 minutes (min) and it was observed that the estrone and P4 levels increased and the luteinizing hormone (LH), follicle stimulating hormone (FSH) and Testosterone concentrations decreased in males. In the same study, it was revealed that the Estrone, E2, Estriol and Pregnandiol concentrations increased in the urine samples taken from men, women, and children. ...
The current study was undertaken to determine the 17-β Estradiol (E2) and Progesterone (P4) levels in different milk products and some baby follow-on milk samples collected from retail markets in Türkiye. For this purpose, a total of 50 samples from 8 different product groups with different fat levels, production technologies, and production series were analyzed for natural P4 and E2 levels using a commercial ELISA kit. The highest E2 level was determined in UHT whole milk (3%) (39.20 ± 6.73 pmol·L-1) while the lowest level was found in buttermilk (26.50 ± 1.85 pmol·L-1) samples. For P4 levels, the highest concentration were found in baby follow-on milk (<1 year old) (45.83 ± 2.95 nmol·L-1) and the lowest values were found in pasteurized milk samples (23.00 ± 6.66 nmol·L-1). Also, in this study, differences among the product groups for E2 and P4 were not found statistically (P>0.05). In conclusion, the natural P4 and E2 were detected in all milk and baby follow-on milks at various levels and generally their levels associated with the product fat level.
... Some researchers (DeMaleki et al., 2010;Ganmaa et al., 2012;Pettersson et al., 2012;Wang et al., 2015) assume possible (direct or indirect) correlation between consumption of milk and dairy products and reproductive disorders or incidence of oncological diseases. According to some studies (Maruyama et al., 2010), men who had been consuming at least 600 mL of cow milk per m 2 of body surface had higher content of steroid hormones (estradiol, estrone and progesterone) in the urine and blood serum. Those men had decreased testosterone and hypophyseal gonadotropins in blood serum approximately one hour after intake of milk. ...
Safety of milk can decline because of high concentrations of steroid hormones like 17β-estradiol, which is associated with the development of some oncological diseases and reproductive disorders. We studied the effects of thermal processing of raw milk and technologies of production of butter and yogurt on the concentration of 17β-estradiol. For this purpose, we determined the amount of 17β-estradiol in raw milk, after pasteurization under different regimes, boiling and during the production of butter and yogurt. Content of 17β-estradiol was determined using the method of immunoenzymatic analysis. We determined that low-temperature processing of milk at the temperature of 77.0 ± 1.0 °С for 1 min caused no changes in the structure of the estrogenic hormone 17β-estradiol, resulting in practically no changes in its amount in pasteurized milk. We determined that 17β-estradiol in milk is a temperature-stable hormone with no tendencies towards significant decrease when subject to high-temperature processing (85.0 ± 1.0 °С for 1 min) and during boiling, because the amount of the hormone decreased on average by 5%. Therefore, we may state that after pasteurization or sterilization, the concentration of 17β-estradiol in drinkable milk would not be significantly different from its initial amount in raw milk. We determined significant increase in 17β-estradiol in butter (3896.1 ± 67.5 pg/g), as compared with the concentration in raw milk (189.4 ± 12.5 pg/mL), and its insignificant content in buttermilk was insignificant (29.3 ± 1.8 pg/mL). The concentration of 17β-estradiol in milk decreased by 25% during 9-month storage at the temperature of –18 °С and by 20% at the temperature of –9 °С. This process can be applied to butter made from milk of cows at late stages of lactation, which contains high level of estrogen. We determined that the steroid hormone 17β-estradiol did not break down under the influence of dairy acid that accumulates as a result of lactic acid fermentation, both with the participation of mixed microflora of raw milk and pure lactic-acid bacteria of fermentation starter for yogurt. The prospects of the studies are the development of a safe maximum allowable level of 17β-estradiol in raw milk and methodological evaluation at a milk-processing factory.
... As milk of pregnant dairy cows is pooled, commercial milk contains higher estrogen amounts compared to former times, when lactation of cows was synchronized and cows gave birth only in spring time. Maruyama et al. [105] analyzed the exposure to exogenous estrogen through the intake of commercial milk produced from pregnant cows in children and adults. Urine concentrations of E1, E2, E3, and pregnanediol significantly increased in all adults and children after intake of 600 ml/m 2 of commercial cow's milk. ...
... These data indicate that the intake of estrogens from cow's milk corresponds to the daily estrogen production rate in prepubertal boys. Maruyama et al. [105] concluded that the intake of cow's milk may be one of the major causes of early sexual maturation in prepubertal children. Peaker of the Hannah Dairy Research Foundation [106] did not consider these pediatric concerns [105] and stated that "even in worst case scenarios, oestrogen consumption in milk is considerably less than regulatory bodies regard as entirely safe." ...
... Maruyama et al. [105] concluded that the intake of cow's milk may be one of the major causes of early sexual maturation in prepubertal children. Peaker of the Hannah Dairy Research Foundation [106] did not consider these pediatric concerns [105] and stated that "even in worst case scenarios, oestrogen consumption in milk is considerably less than regulatory bodies regard as entirely safe." Nevertheless, BCa cells are able to convert E1 sulfate into the 10 times more biologically active E2 [107]. ...
Purpose of Review
This review evaluates cow milk’s impact on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer (BCa) pathogenesis.
Recent Findings
Recent prospective cohort studies support the association between cow’s milk consumption and the risk of estrogen receptor-α-positive (ER⁺) BCa. Milk is a complex biological fluid that increases systemic insulin-like growth factor 1 (IGF-1), insulin and estrogen signaling, and interacting hormonal promoters of BCa. Further potential oncogenic components of commercial milk include exosomal microRNAs (miR-148a-3p, miR-21-5p), bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with BRCA1 loss-of-function mutations and FTO and IGF1 gain-of-function polymorphisms enhancing IGF-1/mTORC1 signaling may be at increased risk for milk-induced ER⁺ BCa.
Summary
Recent prospective epidemiological and pathobiochemical studies identify commercial milk consumption as a critical risk factor of ER⁺ BCa. Large meta-analyses gathering individuals of different ethnic origins with milk derived from dairy cows of varying genetic backgrounds and diverse feeding procedures as well as missing data on thermal processing of milk (pasteurization versus ultra-heat treatment) make multi-national meta-analyses unsuitable for BCa risk estimations in susceptible populations. Future studies are required that consider all vulnerable periods of breast carcinogenesis to cow’s milk exposure, beginning during the perinatal period and puberty, since these are the most critical periods of mammary gland morphogenesis. Notwithstanding the need for better studies including detailed information on milk processing and vulnerable periods of human breast carcinogenesis, the available evidence suggests that dietary guidelines on milk consumption may have to be reconsidered.
... En plus, le calcium est considéré comme un agent chimiopréventif potentiel qui réduit le cancer du côlon en se liant à certaines substances (acides biliaires et acides gras libres) dont l'effet est toxique sur les cellules épithéliales coliques ; et en induisant la différenciation cellulaire lorsqu'elle pénètre à l'intérieur de ces cellules (179). D'un autre côté, les produits laitiers peuvent également contenir des graisses, des hormones et des facteurs de croissance, qui peuvent favoriser la croissance tumorale(180). Par conséquent, cette composition compliquée des produits laitiers peut expliquer l'incohérence des résultats épidémiologiques trouvée dans cette revue systématique. ...
... 8−10 Apart from this, an increased intake of dairy products is also closely related to increased risk of testicular cancer, 11 and altered maturation of prepubertal children. 12 In a study, Afeiche et al. 13 determined an inverse relationship between the dairy food intake and certain semen parameters like sperm morphology and progressive motility among humans. ...
The recent reports on milk consumption and its associated risk with hormone related disorders necessitates the evaluation of dairy products for the presence of endocrine disrupting chemicals (EDCs) and ensure the safety of consumers. In view of this, we investigated the possible presence of (anti)androgenic contaminants in raw and commercialized milk samples. For this purpose, a novel HepARE-Luc cell line that stably expresses human androgen receptor (AR) and the androgen responsive luciferase reporter gene was generated and used in the present study. Treatment of this cell line with androgens and corresponding antiandrogen (flutamide) stimulated or inhibited expression of reporter luciferase, respectively. Real time polymerase chain reaction and immunostaining results exhibited transcription response and translocation of AR from the cytoplasm to the nucleus in response to androgen. Observations implied that a cell-based xenobiotic screening assay via AR response can be conducted for assessing the (anti)androgenic ligands present in food chain including milk. Therefore, the cell line was further used to screen the (anti)androgenic activity of a total of 40 milk fat samples procured as raw or commercial milk. Some of the raw and commercial milk fat samples distinctly showed antiandrogenic activities. Subsequently, some commonly used environmental chemicals were also evaluated for their (anti)androgenic activities. Initial observations with molecular docking studies of experimental compounds were performed to assess their interaction with AR ligand binding domain. Furthermore, (anti)androgenic activities of these compounds were confirmed by performing luciferase assay using the HepARE-Luc cell line. None of the test compounds showed androgenic activities rather some of them like Bisphenol A (BPA) and rifamycin showed antiandrogenic activities. In conclusion, our results provide a valuable information about the assessment of (anti)androgenic activities present in milk samples. Overall, it is proposed that a robust cell-based CALUX assay can be used to assess the (anti)androgenic activities present in milk which can be attributed to different environmental chemicals present therein.
... Commercial milk, being from pregnant cows, often contains a wealth of progesterone. The present data shows that daily intake of commercial milk may be a primary cause of precocious puberty among prepubertal children (Maruyama et al. 2010). Developed countries, such as American and Japan, widely recommended children to take in dairy products. ...
Agricultural product contamination by endocrine-disrupting compounds (EDCs) residues is an international public health issue and requires continuously stringent administration. A high-throughput biotin-streptavidin-amplified enzyme-linked immunosorbent assay (BA-ELISA) for detection of progesterone (P4) has been established to be applied in determining milk samples. Under experimental optimization, BA-ELISA based on anti-P4-specific antibody (P4-pAb-based BA-ELISA) showed a linear range from 0.44 to 31.06 ng/mL. The IC50 was 3.68 ng/mL, and the limit of detection (LOD) was 1.25 × 10−1 ng/mL, with negligible cross-reactivities on structural P4 analogues. The signal amplification system enhanced sensitivity on account of strongly supramolecular affinity between biotin and streptavidin. Good recoveries ranged from 87.81 to 113.11%, and low coefficient of variation (below 9.75%) of the immunoassay validated the feasibility and applicability to monitor P4 in milk samples. Milk samples with different spiked levels were tested by both the established P4-pAb-based BA-ELISA and liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Our results, combined with the advantages of specific antibodies, elucidated that P4-pAb-based BA-ELISA is an applicable method for routine screening analysis of P4.
... Furthermore, lower AMACR intensity was associated with higher PSA levels and more advanced clinical stage at diagnosis, and there was a nonsignificant trend for higher risk of lethal outcomes [370] . In contrast, other studies report AMACR overexpression as an early event in prostate tumorigenesis that may precede morphologic evidence of malignant transformation [371,372] . ...
This review analyzes the potential impact of milk-induced signal transduction on the pathogenesis of prostate cancer (PCa). Articles in PubMed until November 2021 reporting on milk intake and PCa were reviewed. Epidemiological studies identified commercial cow milk consumption as a potential risk factor of PCa. The potential impact of cow milk consumption on the pathogenesis of PCa may already begin during fetal and pubertal prostate growth, critical windows with increased vulnerability. Milk is a promotor of growth and anabolism via activating insulin-like growth factor-1 (IGF-1)/phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin complex 1 (mTORC1) signaling. Estrogens, major steroid hormone components of commercial milk of persistently pregnant dairy cows, activate IGF-1 and mTORC1. Milk-derived signaling synergizes with common driver mutations of the PI3K/AKT/mTORC1 signaling pathway that intersect with androgen receptor, MFG-E8, MAPK, RUNX2, MDM4, TP53, and WNT signaling, respectively. Potential exogenously induced drivers of PCa are milk-induced elevations of growth hormone, IGF-1, MFG-E8, estrogens, phytanic acid, and aflatoxins, as well as milk exosome-derived oncogenic microRNAs including miR-148a, miR-21, and miR-29b. Commercial cow milk intake, especially the consumption of pasteurized milk, which represents the closest replica of native milk, activates PI3K-AKT-mTORC1 signaling via cow milk’s endocrine and epigenetic modes of action. Vulnerable periods for adverse nutrigenomic impacts on prostate health appear to be the fetal and pubertal growth periods, potentially priming the initiation of PCa. Cow milk-mediated overactivation of PI3K-AKT-mTORC1 signaling synergizes with the most common genetic deviations in PCa, promoting PCa initiation, progression, and early recurrence.
... An emerging health issue is a concern about estradiol in cow milk. Milk consumption can increase serum estradiol levels [26]. The use of dairy milk was found in the Adventist Health Study-2 cohort to be positively associated with the risk of breast cancer [27]. ...
A growing number of people are seeking a non-dairy plant-based beverage both for their personal health, and for the health of the planet. The aim of this study was to conduct a cross-sectional survey of single-serve plant-based beverages to assess their nutritional content and health profile. A total of 51 non-dairy plant-based beverages were analyzed from the nutrition label listed on the commercial package. The various beverages contained extracts of soy (n = 14), almonds (n = 13), oats (n = 12), peas (n = 7), banana (n = 2), coconut (n = 2), and rice (n = 1). Almost one-half (45%) of the single-serve beverages had 5 g or more of protein/serving. A total of 75% and 65% of the single-serve beverages had calcium and vitamin B12 levels, respectively, fortified to at least 20% of the Daily Value (DV), while only 28% had vitamin D fortification at the 20% DV level. Two-thirds of the single-serve beverages had high sugar levels, while 39% were low in sodium, 63% were low in fat, and 96% were low in saturated fat. The single-serve plant-based beverages had more protein, calcium, vitamin B12, and sugar but less fat than the non-dairy, multi-serve plant-based beverages/ serving. A limited number of single-serve beverages met the requirements of school meal programs.
