Import Milk Act/ Filled Milk Act 4. Federal Caustic Poison Act Bioterrorism Act 5. Public Health Service Act, Part, PartF, Subpart 1, Biologic Products 6. Title 21 CFR Subpart E - Imports.
AbstractThe associations between milk intake frequency and milk fat consumption and telomere length, an index of biological aging, were studied using an NHANES sample of 5,834 U.S. Adults and a cross-sectional design.
The milk consumption variables were assessed with the NHANES Diet Behavior and Nutrition questionnaire. The quantitative polymerase chain reaction method was used to measure leukocyte telomere length. Results showed that milk consumption frequency was not related to telomere length; however, there was a strong association between milk fat intake and telomere length. With the sample delimited to milk drinkers only, milk fat intake was linearly and inversely related to telomere length, after adjusting for the covariates (, ). For each 1 percentage point increase in milk fat consumed (e.g., 1% to 2%), adults had more than 4 years of additional biological aging. With milk fat intake divided into 5 categories (i.e., milk abstainers, nonfat, 1%, 2%, and full-fat milk), mean telomere lengths differed across the categories (, ). The mean telomere difference between the extremes of milk fat intake (nonfat vs.
Full-fat) was 145 base pairs, representing years of additional biological aging for full-fat milk consumers. Effect modification testing indicated that the milk fat and cellular aging association may be partly due to saturated fat intake differences across the milk fat groups. When the sample was delimited to adults reporting only high total saturated fat intake (tertile 3), the milk fat and telomere relationship was strong. However, when the sample was restricted to adults reporting only low saturated fat consumption (tertile 1), there was no relationship between milk fat intake and telomere length.
Overall, the findings highlight an association of increased biological aging in U.S. Adults who consumed high-fat milk. The results support the latest Dietary Guidelines for Americans (2015–2020), which recommend consumption of low-fat milk, but not high-fat milk, as part of a healthy diet. IntroductionInvestigations evaluating the effect of adult milk consumption on health and disease have produced inconsistent findings.
Some studies indicate that the consumption of cow’s milk promotes health, while others show that it increases risk of disease and mortality. Numerous investigations highlight the mixed results.In a 2018 study by Feskanich et al. , milk intake was associated with a lower risk of hip fracture, whereas in a 2018 investigation by Michaelsson et al., milk consumption was linked to an increased risk of hip fracture. Further, a meta-analysis that included six studies focusing on women and three of men concluded that milk intake and hip fracture are unrelated.In a meta-analysis of 19 studies concentrating on colorectal cancer, Aune et al. determined that milk intake reduces risk, whereas in an evaluation of 32 investigations, the same researcher concluded that milk consumption increases risk of prostate cancer. Similarly, some research indicates that dairy intake reduces the risk of type II diabetes , , whereas other studies show that dairy consumption is linked to increased insulin resistance –. Several investigations have concluded that dairy intake is unrelated to type II diabetes and associated metabolic factors ,.
Lastly, in a Japanese cohort, milk intake was inversely associated with all-cause mortality , but in a Swedish group, milk consumption was related to increased all-cause mortality.Clearly, the effects of adult milk consumption on health and disease are varied, and in recent years, questions about the influence of milk have been further complicated with debate about the effect of milk fat on disease risk. Is low-fat milk a healthier choice than full-fat?
According to a 2017 study by Tognon et al., all-cause mortality is significantly higher among adults who consumed full-fat milk compared to medium- or low-fat milk. Similarly, Talaei et al. Found that Iranians who drink whole milk daily are at higher risk of all-cause mortality than their counterparts.
Likewise, whole milk intake is predictive of elevated prostate cancer mortality in studies by Lu et al. and Song et al. Conversely, according to Crichton and Alkerwi, high intake of whole-fat dairy is inversely associated with obesity and abdominal adiposity compared to those with low consumption. Additionally, research by Drehmer et al. Shows that full-fat, but not low-fat, dairy is favorably related to the metabolic syndrome in adults.The effects of milk and milk fat on cancer, heart disease, diabetes, and all-cause mortality have been reviewed extensively in the literature.
With some investigations showing positive outcomes and others revealing negative, there remains much to learn about the effect of cow’s milk on health and disease in adults. The influence of milk fat, particularly low-fat compared to full-fat, also needs clarification.To date, the influence of milk and milk fat on inflammation, oxidative stress, and cellular longevity has received little attention. Cellular longevity is often indexed objectively by measuring the length of telomeres ,.
Adults with short telomeres tend to have more oxidative stress and chronic disease, including more heart disease, depression, obesity, and cancer, as well as earlier death, than their counterparts –.Telomeres add stability to and help safeguard chromosomes. Telomeres cap the ends of chromosomes with nucleoproteins.
A simple analogy is that telomeres function like the caps that protect the end of shoe laces. Over time, as cells divide, telomeres become progressively and predictably shorter.Although chronological age is the key factor accounting for the length of telomeres, other things contribute significantly.
Research shows that oxidative stress is a critical factor ,. Moreover, lifestyle plays a major role. For instance, people who smoke have shorter telomeres than nonsmokers.
Adults with obesity have shorter telomeres than their counterparts , and inactive individuals have shorter telomeres than those who are physically active.Biological aging is also affected by diet. Regular intake of healthy foods like nuts and seeds is associated with longer telomeres , whereas consumption of less healthy foods, like processed meats, is related to shorter telomeres. Fiber intake goes hand-in-hand with longer telomeres , as does higher vegetable intake and regular fruit consumption. However, consumption of fats and oils is associated with shorter telomeres and increased biological aging ,.From a more physiological and molecular nutrition perspective, milk is a postnatal endocrine signaling system.
Milk consumption encourages mTORC1-mediated anabolism and growth. For example, extended full-fat cow’s milk consumption in mice increases energy intake and body weight and reduces insulin signaling in white adipose tissue compared to low-fat milk intake. According to Melnik, to accomplish its mTORC1-activating role, four metabolic messengers are provided by milk: “1. Essential branched-chain amino acids, 2. Glutamine, 3. Palmitic acid, and 4. Bioactive exosomal microRNAs”.Research by Yasuda et al.
Indicates that unsaturated and saturated fatty acids have opposite effects on podocyte apoptosis by controlling mTORC1 activity via translocation onto lysosomal membranes. Insulin and IGF-1 and essential branched-chain amino acids influence mTORC1 by activation of the kinase AKT pathway. Palmitic acid, the primary saturated fatty acid of milk fat globules, also activates mTORC1 at the lysosome. In short, it appears that repeated mTORC1 activation contributes to endoplasmic reticulum stress, leading to premature aging and disease.Although much is understood about diet, oxidative stress, and cellular longevity, the role of cow’s milk consumption, particularly milk fat, remains unclear. To date, the relationship between milk fat intake and telomere length has rarely been studied.
Hence, the present study was conducted. Its purpose was to determine the extent cow’s milk consumption and the fat content of the milk account for differences in cellular aging, indexed using leukocyte telomere length in 5,834 women and men, representative of the U.S. Adult population. A secondary objective was to assess the extent demographic, lifestyle, and other dietary factors influence the milk and telomere relationships. The role of saturated fat intake, a major part of the fat content of cow’s milk, was also a significant focus of the investigation. Materials and Methods 2.1.
SampleFor a number of decades, the National Health and Nutrition Examination Survey (NHANES) has been conducted in the United States. NHANES is a government-sponsored research program administered by the National Center for Health Statistics.
The purpose of NHANES is to evaluate the health and nutrition status of children and adults in the United States and to track national trends over time using physical examinations, interviews, and laboratory tests.NHANES recruits participants using a four-stage, probability sampling design. Consequently, if analyzed correctly using individual sample weights, results are generalizable to the U.S. Although NHANES data have been collected for many decades, telomere data are only available for four years, 1999-2002. Data containing telomere values have been available for public use since the end of 2014. NHANES data are cross-sectional and free and can be accessed by the public online ,.During the few years that telomere data were collected by NHANES, only individuals who were at least 20 years old were given the opportunity to give a sample of DNA. Of the 10,291 eligible participants, a total of 7,827 useable DNA samples were obtained. Individuals who were 85 years or older were not included in the present sample because NHANES recorded the age of all these adults as 85 years, truncating their ages, to safeguard privacy.Each NHANES subject was required to give written informed consent to participate.
Moreover, approval to collect the individual data and post it online without identifying information was approved by the Ethics Review Board of the National Center for Health Statistics. MeasurementsIn this investigation, there were two exposure variables: (1) frequency that cow’s milk was consumed and (2) the milk fat content of the milk consumed. The outcome variable was leukocyte telomere length, a marker of biological aging. There were a dozen covariates controlled in the present study (age, gender, race, household size, smoking, body mass index, MET-minutes of total physical activity, alcohol use, grams of protein consumed per kilogram of body weight, percentage of energy derived from dietary fat, grams of dietary fiber consumed per 1000 kilocalories, and percentage of total energy derived from saturated fat. Milk ConsumptionThe Diet Behavior and Nutrition section of the NHANES questionnaire was used to collect data on milk consumption. One question focused on frequency of milk consumption during the past 30 days. The specific NHANES question was: “Now I’m going to ask a few questions about milk products.
Do not include their use in cooking. In the past 30 days, how often did you have milk to drink or on your cereal? Please include chocolate and other flavored milks as well as hot cocoa made with milk.
Do not count small amounts of milk added to coffee or tea.” Possible responses were: Never; Rarely—less than once a week; Sometimes—once a week or more, but less than once a day; or Often—once a day or more. Participants could also indicate that their milk consumption is “Varied.” Only 37 individuals selected the “Varied” option, which is an insufficient subsample to analyze according to NHANES, so the “Varied” group was excluded from the analyses.Participants who indicated that they drank milk were asked: “What type of milk was it? Was it usually?” Possible responses were: You drink whole or regular milk; You drink 2% fat milk; You drink 1% fat milk; You drink skim, nonfat, or.5% milk (which includes reconstituted from dry); or You drink another type of milk. Subjects who reported that they drink a milk type other than cow’s milk ( ), such as almond milk and soy milk, were excluded from the study.
Individuals who indicated that they do not drink milk were labeled milk abstainers for both the milk frequency question and the milk fat question.Concurrent validity was shown for both the milk consumption frequency question and the milk fat measure. Specifically, adults reporting that they consumed milk Rarely, Sometimes, or Frequently consumed more saturated fat than adults who never consumed milk. Those reporting that they consumed milk Frequently or Sometimes had higher protein intakes than those indicating that they consumed milk Rarely or Never. Additionally, adults consuming full-fat or 2% milk had higher total dietary fat intakes than milk abstainers and those consuming nonfat milk. Similarly, those who consumed full-fat or 2% milk consumed higher levels of saturated fat than milk abstainers and those drinking 1% milk or nonfat milk.Information about the thermal processing of milk was not collected by the NHANES questionnaire. Specifically, no data were gathered about milk pasteurization versus ultra-heat-treated (UHT) milk.
This is a study limitation because milk-derived miRNAs survive pasteurization, and recent research shows that miRNAs may play a role in telomere length. Telomere LengthAccording to NHANES , “the telomere length assay was performed in the laboratory of Dr. Elizabeth Blackburn at the University of California, San Francisco, using the quantitative polymerase chain reaction method to measure telomere length relative to standard reference DNA (T/S ratio), as described in detail elsewhere ,. Each sample was assayed 3 times on 3 different days. The samples were assayed on duplicate wells, resulting in 6 data points.
Sample plates were assayed in groups of 3 plates, and no 2 plates were grouped together more than once. Each assay plate contained 96 control wells with 8 control DNA samples. Assay runs with 8 or more invalid control wells were excluded from further analysis (0 and 0. Descriptive characteristics of the sample ( ).As shown in Table, nearly half of U.S. Adults consumed milk daily and another 1 in 4 consumed milk at least weekly, but not daily. Approximately 30% of U.S. Adults reported consuming full-fat milk and another 30% drank 2% milk.
Combined, about 60% of U.S. Adults reported drinking high-fat milk. On the other hand, 10% reported consuming 1% milk and another 17% indicated they drank nonfat milk. Combined, about 27% reported drinking low-fat milk. About 13% reported never consuming cow’s milk.The weighted% column shows the distribution of subjects after the NHANES sample weights were applied. The weighted% values are more meaningful than the number of subjects because they take into account the sample weights and reflect the percentage of the U.S. Population that practice the behavior.These results are similar to those from the most recent NHANES data available.
Recent NHANES data show that approximately 36% report consuming 2% milk and another 21% drink full-fat milk. Approximately 13% drink nonfat milk and 10.5% indicate 1% milk. Hence, in recent years, 57% drink high-fat milk and 23.5% report drinking low-fat milk. These recent NHANES milk data could not be used in the present study because telomere data were not available during these years.An inverse, linear relationship was detected between chronological age and telomere length. Leukocyte telomeres were 15.3 base pairs shorter for each additional year of age (, ). The Pearson correlation was inverse and significant (, ).
Beyond the linear association, telomere length was not related to age-squared (, ).Table shows that the mean length of telomeres did not differ across levels of milk consumption frequency in U.S. Telomere length differences were not significant after adjusting for the demographic, lifestyle, and/or dietary covariates. SE is the standard error of the mean. The four levels of milk consumption frequency were as follows: Never: participants who never consumed milk (, 14.0%); Rarely: adults who consumed milk. Differences in mean telomere length (base pairs) by frequency of milk consumption in U.S. Women and men, after adjusting for the covariates ( ).Table indicates that mean telomere lengths differed across levels of milk fat consumption, after controlling for the demographic covariates, the demographic and lifestyle covariates, and the dietary covariates, in addition to the other covariates. After adjusting for all the covariates, adults who consumed full-fat or 2% milk had shorter telomeres than those who consumed nonfat or 1% milk.
The difference in telomere length was 145 base pairs. Similarly, milk abstainers had shorter telomeres than those consuming nonfat milk or 1% milk.
Consumers of nonfat milk had telomeres that were 115 base pairs longer than those who did not drink cow’s milk, on average. Telomere length did not differ among those who consumed full-fat milk and 2% milk or who were milk abstainers.
Adults who consumed nonfat or 1% milk had statistically equal mean telomere lengths. The five levels of milk fat consumption were defined as follows: abstainer: participants who never consumed milk (, 14.0%); full-fat: adults who typically consumed whole or full-fat milk (, 35.9%); 2%: subjects who usually consumed 2% milk (, 28.3%); 1%: individuals who typically consumed 1% milk (, 8.7%); and nonfat: participants who typically consumed nonfat, skim, or 0.5% milk (, 13.2%). The number of subjects in each category does not take into account the sample weights assigned to each subject. However, the percentage (%) following sample size shows the proportion of subjects in the milk fat category with the NHANES sample weights applied.
SE is the standard error of the mean. A,bMeans on the same row with the same superscript letter are not statistically different ( ).
Model 1 compares telomere means, after adjusting for the demographic covariates. In Model 1, the mean difference in telomere length between milk abstainers and those who consumed 1% milk was. Model 2 compares telomere means, after controlling for the demographic covariates and the lifestyle covariates. In Model 2, the difference in telomere length between abstainers and those who consumed 1% milk was. Model 3 compares telomere means, after adjusting for the demographic, lifestyle, and dietary covariates. Differences in mean telomere length (base pairs) by level of milk fat content consumed by U.S. Men and women, after adjusting for the covariates ( ).With milk fat intake treated as a continuous variable and milk abstainers held out of the analysis, milk fat content was linearly and inversely related to telomere length, after adjusting for differences in the demographic variables (, ) and the demographic and lifestyle measures (, ) and after controlling for the demographic, lifestyle, and dietary variables together (, ).
With all the covariates controlled, for each increment of 1 percentage point of milk fat (e.g., 1% to 2% milk fat, or 2% to 3%), telomeres were 69 base pairs shorter, on average.The effect modification was tested with subjects stratified according to milk consumption frequency levels. Results showed that the relationship between milk fat content and telomere length was significant when the sample was delimited to adults who consumed milk “Often” (daily or more) or “Sometimes” (at least weekly, but not daily), as displayed in Table. However, when the sample was delimited to adults who consumed milk “Rarely,” there was no association between milk fat content and biological aging. A,bMeans on the same row with the same superscript letter are not significantly different. SE is the standard error of the mean. For each row, the sample is delimited to the milk consumption frequency category listed in the first column. For the first row (Often), the sample sizes for full-fat, 2%, 1%, and nonfat were (28.9%), (34.3%), (12.7%), and (24.1%), respectively.
For the second row (Sometimes), the sample sizes were (37.3%), (34.5%), (11.8%), and (16.4%), respectively. For the third row (Rarely), the sample sizes were (46.8%), (35.1%), (7.0%), and (11.2%), respectively.
The sample size percentages were derived using individual sample weights and therefore represent the U.S. Adult population.
The sample size numbers do not. Means on each row were adjusted for differences in all the covariates. Differences in mean telomere lengths (base pairs) by level of milk fat content, after adjusting for all the covariates, with the sample delimited to one milk consumption frequency group at a time.The effect modification was also evaluated with participants separated into tertiles based on total saturated fat intake (percent of total energy derived from saturated fat). With the sample delimited to adults with high levels of total saturated fat intake (tertile 3), the relationships between milk fat intake and telomere length were stronger for Model 2 (, ) and Model 3 (, ), while Model 1 (, ) was similar to the association shown in Table, based on the total sample.
With the sample confined to adults with only moderate intakes of total saturated fat (tertile 2), the relationships between milk fat consumption and telomere length were weaker, but remained significant, for Model 1 (, ), Model 2 (, ), and Model 3 (, ), compared to models shown in Table based on the total sample. With the sample restricted to U.S. Adults who only consumed low levels of total saturated fat (tertile 1), none of the models were statistically significant.Table displays the extent the dietary covariates (i.e., protein, total dietary fat, fiber, and saturated fat) differed across the five milk fat content categories. Adjustments were made for differences in the demographic covariates. Results showed that all the relationships were statistically significant (Table ).
Adults who did not drink cow’s milk consumed less protein than any of the other groups (, ). Also, nonfat milk drinkers consumed less fat than any of the other groups. On the other hand, adults who drank full-fat milk or 2% consumed more dietary fat than abstainers and nonfat milk drinkers (, ). Moreover, milk abstainers and those who drank nonfat milk consumed less saturated fat than adults who drank full-fat, 2%, or 1% milk (, ). Lastly, nonfat milk drinkers consumed more dietary fiber than any of the other milk fat groups, and those who drank full-fat milk ate less fiber than any of the other milk fat groups (, ), as shown in Table.
SE is the standard error of the mean. Protein (g/kg) refers to grams of protein intake per kilogram body weight. Fat (% kcal) represents the percentage of total energy derived from dietary fat. Fat (% kcal) refers to the percentage of total energy derived from saturated fat. Fiber (g/1000 kcal) represents the number of grams of fiber consumed per day per 1000 kcal.
The nonfat milk category also included skim milk and 0.5% milk. Means on each row were adjusted for differences in the demographic variables.
A,b,c,dMeans on the same row with the same superscript letter are not statistically different ( ). On the row for fiber intake, the mean difference between abstainers and adults who drank 2% milk was borderline significant ( ). On the row for fat (% kcal), the difference between milk abstainers and those drinking nonfat milk was borderline significant ( ). The five levels of milk fat consumption were defined as follows: abstainer: participants who never consumed milk (, 14.0%); full-fat: adults who consumed full-fat milk (, 35.9%); 2%: subjects who usually consumed 2% milk (, 28.3%); 1%: individuals who consumed 1% milk (, 8.7%); and nonfat: participants who typically consumed nonfat, skim, or 0.5% milk (, 13.2%). The number of subjects in each category above does not take into account the sample weights assigned to each subject. However, the percentage (%) following the sample size shows the proportion of subjects in the milk fat category with the NHANES sample weights applied. The% values are more meaningful than the number of subjects ( ) because the percentages represent the proportion of the U.S.
Adult population that fall within each milk fat category.