Mind the gap: Contesting normal/abnormal constructs of human biology and behaviors.

Training in anthropology and evolutionary science ideally prepares scholars to recognize and challenge culturally grounded views of human variation. But upon inspection we find that idealized, and thus perhaps biased, conceptualizations of what is "normal" continue to permeate evaluations of human biology and behaviors. Each of the 13 contributions in this special issue on biological normalcy tackles these concerns as they pertain to some universal, but also variable, human biological or behavioral phenotype. These papers consider the ways in which the term "normal" is used in everyday life, in biomedicine, and in scientific studies to characterize some portion of the variability in a human phenotype. The contributors to this special issue, some of whom present original research findings, discuss the ongoing debates and challenges in the study of human biology and behavior, and critically examine how "normal" is used in their specific research area, thereby exposing and countering biases in the discourse on human phenotypic variation.

Marginal Food Security Predicts Earlier Age at Menarche Among Girls From the 2009-2014 National Health and Nutrition Examination Surveys.

STUDY OBJECTIVE: This study analyzed the relationship between household food security and variation in age at menarche, as well as the connections between food insecurity, nutritional status, and allostatic load, among girls aged 12-15 years from the 2009-2014 United States National Health and Nutrition Examination Survey (NHANES). METHODS: Data analysis included mean comparisons of age at menarche among household food security groups (high, marginal, low, and very low) as well as categorical variables known to associate with age at menarche (ethnicity, poverty status, body mass index [BMI], allostatic load, and milk consumption). χ2 Analyses were used to test the associations between household food security and additional categorical variables. Univariate and multivariate regression models were used to test the relationship between variation in age at menarche and household food security, ethnicity, BMI, and allostatic load categories while controlling for age. RESULTS: Non-Hispanic Black and Hispanic/Mexican American girls had earlier mean ages at menarche, higher mean BMIs, and disproportionately experienced household food insecurity when compared to non-Hispanic White-identifying girls. In the univariate analyses, marginal household food security, Hispanic/Mexican American and Black ethnicities, overweight and obese BMI categories, and marginal-high allostatic load were each associated with lower age at menarche compared to reference categories. These associations were maintained in the multivariate analysis, although only Hispanic/Mexican American ethnicity predicted earlier menarche when compared to that of non-Hispanic White girls. CONCLUSIONS: Marginal household food security, particularly for girls who identified as non-White, predicted earlier age at menarche independent of nutritional status and allostatic load. At the same time, having more energetic resources (ie, higher BMI) also significantly predicted earlier menarche.

Pearl lecture: Biological normalcy: A new framework for biocultural analysis of human population variation.

Biological normalcy is a new analytical framework for understanding the bi-directional relationships between the biology of populations and cultural norms. Populations are characterized by statistical distributions-that is, measures of central tendency and variance-for biological traits, and these co-exist in societies with ideas about what constitutes "normal" human bodies, that is, normative views about what bodies "should" be like. While statistical norms may carry no explicit evaluative weight, the question is how they are related to judgments about what is "normal" or "abnormal." In a 1947 paper, Margaret Mead recognized their potential relationship: "normal…may refer to the statistically usual in the culture-usually without any recognition that this is culturally relative-so that the statistically usual is identified with the basically human…." Despite her observations over 70 years ago, little has been done on this topic, yet such work promises new insights into the relationship between culture and biology, here described at the population level, rather than as individual genetic characteristics. Using examples of sex/gender, race/ethnicity, age, and my work on human variation in the ability to drink milk, I outline the ways in which statistical norms may: influence individuals' perceptions of what is "normal" (Mead's "basically human"); lead to normative judgments about what human biology "should" be ("ethno-biocentrism") that are reinforced by biases in discourse about human variation; and potentially feedback to mold the biological characteristics of a population.

IGF-I and IGFBP-3 concentrations at 2 years: associations with anthropometry and milk consumption in an Indian cohort.

BACKGROUND/OBJECTIVES: To ascertain associations between plasma insulin-like growth factor I (IGF-I), insulin-like growth factor-binding protein 3 (IGFBP-3) and their molar ratio at 2 y with neonatal size, infant growth, body composition at 2 y, and feeding practices in an Indian cohort. SUBJECTS/METHODS: A cohort of 209 newborns, with 122 followed at 2 y. Anthropometry was conducted at birth and 2 y. IGF-I and IGFBP-3 concentrations were measured in cord blood and at 2 y. Maternal and child diet was assessed by food frequency questionnaires and maternal interviews. Multivariate regression was used to test for associations adjusting for confounding factors. RESULTS: Mean 2 y plasma IGF-I and IGFBP-3 concentrations and IGF-I/IGFBP-3 were 49.4 ng/ml (95% CI: 44.1, 54.8), 1953.8 ng/ml (CI: 1870.6, 2036.9) ng/ml, and 0.088 (CI: 0.081, 0.095), respectively. IGF-I and IGF-I/IGFBP-3 were positively associated with current length, but not body mass index or adiposity. IGF-I was higher among those with greater change in length since birth. IGF-I concentrations were higher in children who drank the most milk (>500 vs. <250 ml per day: 65.6 vs. 42.8 ng/ml, p < 0.04), received other milk <6 months compared to ≥6 months (56.3 vs. 44.8 ng/ml, p < 0.05), and in those whose mothers consumed milk daily vs. less frequently in late pregnancy (56.4 vs. 42.7 ng/ml, p < 0.01). In multivariate regression, 2 y IGF-I concentration and IGF-I/IGFBP-3 were each positively associated with current length and milk intake. IGFBP-3 was not related to anthropometry or milk intake. CONCLUSIONS: Plasma IGF-I concentrations and IGF-I/IGFBP-3 at 2 y are positively associated with length at 2 y and current milk intake.

Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans.

Alpha-amylase exists across taxonomic kingdoms with a deep evolutionary history of gene duplications that resulted in several α-amylase paralogs. Copy number variation (CNV) in the salivary α-amylase gene (AMY1) exists in many taxa, but among primates, humans appear to have higher average AMY1 copies than nonhuman primates. Additionally, AMY1 CNV in humans has been associated with starch content of diets, and one known function of α-amylase is its involvement in starch digestion. Thus high AMY1 CNV is considered to result from selection favoring more efficient starch digestion in the Homo lineage. Here, we present several lines of evidence that challenge the hypothesis that increased AMY1 CNV is an adaptation to starch consumption. We observe that α- amylase plays a very limited role in starch digestion, with additional steps required for starch digestion and glucose metabolism. Specifically, we note that α-amylase hydrolysis only produces a minute amount of free glucose with further enzymatic digestion and glucose absorption being rate-limiting steps for glucose availability. Indeed α-amylase is nonessential for starch digestion since sucrase-isomaltase and maltase-glucoamylase can hydrolyze whole starch granules while releasing glucose. While higher AMY1 CN and CNV among human populations may result from natural selection, existing evidence does not support starch digestion as the major selective force. We report that in humans α-amylase is expressed in several other tissues where it may have potential roles of evolutionary significance.

Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach.

OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences.

Milk intake and total dairy consumption: associations with early menarche in NHANES 1999-2004.

BACKGROUND: Several components of dairy products have been linked to earlier menarche. METHODS/FINDINGS: This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Two samples were utilized: 2657 women age 20-49 yrs and 1008 girls age 9-12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5-12 yrs and age at menarche (daily milk intake ß = -0.32, P<0.10; "sometimes/variable milk intake" ß = -0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk "sometimes/varied" or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9-12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight. CONCLUSIONS: There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.

Dairy and milk consumption and child growth: Is BMI involved? An analysis of NHANES 1999-2004.

Humans are unique among mammals in that many consume cow's milk or other dairy products well beyond the traditional age of weaning. Milk provides various nutrients and bioactive molecules to support growth and development, and the question arises as to whether this dietary behavior influences growth parameters. There is evidence that milk makes positive contributions to growth in height, but its associations with other aspects of body size, such as body mass index (BMI), are not well-established. National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and multivariate regression analysis were used to test the hypothesis that milk (g) or total dairy product consumption (kJ) is associated with higher BMI percentile among US White, Black, and Mexican-American children of age 2-4 years (n = 1,493) and 5-10 years (n = 2,526). Younger children in the highest quartile of dairy intake had higher BMIs (beta = 7.5-8.0; P < 0.01) than those in the lowest two quartiles. Controlling for energy intake eliminated differences between QIV and QI. Among children of 5-10 years of age dairy intake had no relationship to BMI. Young children in the highest quartile of milk intake had higher BMIs than all lower quartiles (beta = 7.1-12.8; beta = 6.3-11.8 in energy-controlled models; P < 0.05). Among children of 5-10 years of age, those in QIV for milk intake had higher BMIs than those in QII (beta = 8.3; beta = 7.1 in energy-controlled model; P < 0.01). Controlling for total protein or calcium did not change the results. Milk had more consistent positive associations with BMI than did dairy products, and these were strongest among children of 2-4 years of age.

Consumption of milk, but not other dairy products, is associated with height among US preschool children in NHANES 1999-2002.

BACKGROUND: Little is known about how cow's milk consumption affects growth of young children. AIM: The present study evaluated associations between milk consumption and height among preschool-age children in three ethnic groups in the USA. SUBJECTS AND METHODS: A sample of 1002 children aged 24-59 months from NHANES 1999-2002 was used. Multivariate regression tested for associations between milk consumption (milk kJ/total kJ from 24 h recall, daily vs less frequent intake over 30 days) and height, controlling for age, sex, ethnicity, birth weight, and energy intake. RESULTS: Children in the highest quartile of milk intake (QIV) were taller (1.1-1.2 cm; p<0.01) than those in QII and QIII but not QI. Total calcium had a positive effect on height (p<0.01), but did not change the height differences among percentiles. Total protein was not associated with height and QIV children were taller (0.9-1.2 cm) than those in all other quartiles. Children who drank milk daily were taller (1.0 cm; p<0.02) than those with less frequent intake. Consumption of other dairy products (other dairy kJ/total kJ) had no association with height. Blacks were taller than Whites and Mexican-Americans; controlling for milk intake did not alter this pattern. CONCLUSION: Milk contributes positively to height among preschool children; this association was not found for non-milk dairy products.

Does milk make children grow? Relationships between milk consumption and height in NHANES 1999-2002.

In the United States, milk (usually cow's milk) is widely considered an "essential food" to support bone growth among post-weaning age children, as evident in government-sponsored nutrition policies that mandate milk for children. Milk contains calories, protein, and calcium, among other nutrients, and bioactive components such as insulin-like growth factor-I (IGF-I), all of which may facilitate bone growth. There is a large literature on milk and/or calcium intake and its effects on bone density, but one aspect of bone mass--height--is not well studied in relation to milk consumption. Limited experimental studies show no consistent relationship across populations. To investigate this linkage among American children, analysis of the NHANES 1999-2002 was undertaken. NHANES data allow two hypotheses to be tested: (1) reported frequency of childhood milk consumption will be positively related to adult height and (2) height of children 5-18 years will be predicted by the reported frequency of milk consumption and/or milk intake from a 24-h dietary recall. Results indicate that adult height was positively associated with milk consumption at ages 5-12 and 13-17, after controlling for sex, education, and ethnicity. Among contemporary children, milk consumption had no effect on the height of 5-11 year olds after controlling for age, birthweight, energy intake, and ethnicity. In contrast, milk consumption frequency and milk intake (measured as grams of milk, or protein or calcium from milk) were significant predictors of the height of 12-18 year olds, along with age, sex, household income, and ethnicity. The greatest ethnic contrasts were between Mexican Americans and non-Hispanic whites and blacks, and milk variables remained significant predictors of height in these comparisons. Thus NHANES data show substantial variability in the effects of milk consumption on height.

The proximate determinants of fertility in populations exposed to chronic hypoxia.

It has been hypothesized that hypoxia reduces fertility, but comparative studies of high and low altitude populations have been unable to verify or refute this proposal because it is difficult to control for the behavioral and sociocultural factors that may also either underlie fertility differentials or compensate for physiological changes caused by varying partial pressure of oxygen. Taken collectively, estimates of fertility in populations exposed to chronic hypoxia range widely and do not suggest any reproductive patterns specific to high altitude. Here we review the available data from the Andes and the Himalaya on the proximate determinants of fertility, that set of factors through which any and all environmental, behavioral, and sociocultural factors must act to influence fertility levels. Although hypoxia could potentially affect some of these factors, there is no unequivocal evidence that this occurs in human populations indigenous to high altitude. At this time, it appears that local variations in infant feeding beliefs and practices, often coupled with prolonged breast-feeding, play a major role in determining fertility variation in Andean populations. In the Himalaya, large numbers of adults are not in sanctioned sexual unions as a consequence of polyandrous marriage practices and religious celibacy. The absence of a clear negative effect of hypoxia on fertility in populations indigenous to high altitude, even though migrants report reproductive difficulties, argues that these populations have adapted to the conditions at high altitude. The experimental and clinical evidence presented in this issue suggests proximate mechanisms by which such adaptation, shaped by natural selection and developmental processes, is possible.

Increasing use of prenatal care in Ladakh (India): the roles of ecological and cultural factors.

Attempts to manage the outcome of pregnancy are ubiquitous among human societies. Those practices are becoming standardized as prenatal care under a biomedically trained practitioner has come to characterize the formal management of pregnancy. However, many women do not seek biomedical surveillance of their pregnancies, and, in many contexts, particularly in 'modernizing' or rural communities, prenatal care facilities are often poorly coordinated and under-utilized for a variety of reasons. This report illustrates widespread and increasing usage of biomedical services for prenatal care and birth among women in Ladakh, India, over the course of the past 20 years. This trend is at odds with that typical of other parts of South Asia, and can be attributed to the unique ecological, cultural, and historical characteristics of this region. These include the hypoxia of this high-altitude region, which poses substantial problems for successful birth outcome, along with the socio-ecology of maternal diet and work patterns that further compromise birth outcome. These risk factors exist in the context of the absence of involvement of traditional institutions such as Tibetan medicine or traditional birth attendants (TBAs) in pregnancy and birth, and government-sponsored efforts to establish institutions of modernity in Ladakh such as biomedical facilities. Hence, the penetration of biomedical services into the domain of reproductive health has been facilitated. Idiosyncratic aspects of the obstetrics practice itself, particularly the social position and personality of the obstetrician, have also played an important role in recruiting women to make use of hospital-based prenatal care and birth. However, despite broader usage of prenatal care and hospital births by Ladakhi women, there is little indication that birth outcomes have improved significantly. Reasons for this lack of measurable success are considered.

Neonatal and maternal anthropometric characteristics in a high altitude population of the western Himalaya.

A study of neonatal anthropometric characteristics was undertaken in Ladakh, India, a region comprising the western portion of the trans-Himalayan plateau. The object was to better understand the dynamics of high altitude adaptation in the Himalaya. In a largely native sample of 168 women and their newborns, mean birth weight was 2,764 g, mean length was 48.02 cm, and mean Ponderal Index (PI) was 2.49. Female newborns were significantly lighter and shorter than males. Overall, 27% of newborns fell into the standard category of infants at increased risk of mortality ( < 2,500 g); 37% of females and 17% of males were so classified. In multivariate regression analysis, maternal weight and the sex and gestational age of the newborn were the only significant predictors of birth weight, but explained a small (18%) part of the variance. Compared to Andean and Tibetan samples, Ladakhi newborns were between 300 and 550 g lighter. This variation is explained, in part, by maternal characteristics, such as lower average parity, age, and weight. Reproductive capacity appears to be compromised in this population because of inadequate nutrition in the face of high energy demands of agricultural work, which may further compromise maternal adaptation to hypoxic conditions. The population of Ladakh has a relatively recent ancestry in this high altitude region and is likely a genetically heterogeneous population from an extensive history of immigration. Thus it is possible that the low average birth weight in Ladakh may also be influenced by inadequate genetic adaptation to hypoxia. © 1994 Wiley-Liss, Inc.