Hemoglobin concentration of pastoral nomads permanently resident at 4,850-5,450 meters in Tibet

This paper presents data on the hemoglobin concentration of a sample of 103 pastoral nomads who are lifelong residents of Phala, at 4,850-5,450 m, on the northern plateau of the Tibet Autonomous Region of the Peoples' Republic of China. This native population resides at the highest altitude of which we are aware and is thus exposed to the most extreme chronic hypoxic stress. However, they do not exhibit the most pronounced physiological adaptations, i.e., hemoglobin concentrations exceeding those found in all other high-altitude populations. Adult male and female mean hemoglobin concentrations of 18.2 and 16.7 gm/dl, respectively, were found. These data, in conjunction with earlier studies of ethnic Tibetans living at 3,400 m, demonstrate a pattern of increasing hemoglobin concentration (erythrocytosis) at increasing altitude of residence in the Himalayas and Tibet. At the same time, however, the hemoglobin concentration is lower than that found among Andean highlanders. These new data raise the possibility of quantitative population differences in hematological adaptation to high altitude hypoxia.     

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800–4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3–4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations. Am J Phys Anthropol 106:385–400, 1998. © 1998 Wiley-Liss, Inc.     

Evaluation of high sensitive C-reactive protein and 5-10 methylenetetrahydrofolate reductase genotype in Japanese young adults

Primary objective: To carry out a preliminary evaluation of subclinical inflammation and its genetic background in young adults.

Research design: Fifty-five healthy Japanese young adults aged 19–27 years (37 males and 18 females, mean age: 22.3 years), and 58 healthy Japanese adults aged 40 to 60 years (21 males and 37 females, mean age: 51.5 years) were included in this study.

Methods and procedures: We measured plasma high-sensitive C-reactive protein (hs-CRP) levels and screened for the C677T polymorphism of the 5-10 methylenetetrahydrofolate reductase gene (MTHFR), which is considered a genetic risk factor for atherosclerosis, by HinfI digestion.

Main outcomes and results: Hs-CRP levels of the young adult group were significantly lower than the levels of the middle aged group (0.014±0.030 mg/dl vs. 0.031±0.040 mg/dl, p=0.005). The levels were significantly higher in males than in females (0.028±0.019 mg/dl vs. 0.013±0.010 mg/dl, p=0.008) among young adults. Furthermore, we evaluated the relationship of the C677T genotype and hs-CRP values, but found no association between them.

Conclusions: Although the sample size is limited, our preliminary study demonstrated the profiles of hs-CRP in Japanese young adults. Further investigation will be needed to establish the guidelines for customized school health education using sensitive laboratory and genetic markers.     

Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia

Research on humans at high-altitudes contributes to understandingthe processes of human adaptation to the environment and evolution.The unique stress at high altitude is hypobaric hypoxia causedby the fall in barometric pressure with increasing altitudeand the consequently fewer oxygen molecules in a breath of air,as compared with sea level. The natural experiment of humancolonization of high-altitude plateaus on three continents hasresulted in two—perhaps three—quantitatively differentarterial-oxygen-content phenotypes among indigenous Andean,Tibetan and Ethiopian high-altitude populations. This paperillustrates these contrasting phenotypes by presenting evidencefor higher hemoglobin concentration and percent of oxygen saturationof hemoglobin among Andean highlanders as compared with Tibetansat the same altitude and evidence that Ethiopian highlandersdo not differ from sea-level in these two traits. Evolutionaryprocesses may have acted differently on the colonizing populationsto cause the different patterns of adaptation. Hemoglobin concentrationhas significant heritability in Andean and Tibetan samples.Oxygen saturation has no heritability in the Andean sample,but does among Tibetans where an autosomal dominant major genefor higher oxygen saturation has been detected. Women estimatedwith high probability to have high oxygen saturation genotypeshave more surviving children than women estimated with highprobability to have the low oxygen saturation genotype. Thesefindings suggest the hypothesis that ongoing natural selectionis increasing the frequency of the high saturation allele atthis major gene locus.     

Growth trends among male Bods of Ladakh--a high altitude population

A random sample of 274 native male Bods of Ladakh ranging in age from 11 to 19 years, living in Leh (Ladakh) at mean altitude of 3,514 metres, was studied. The pattern of growth of this sample was compared with the sea level Indians. The results indicate that: (1) The so called adolescent spurt is not well defined among Bod highlanders. (2) Bods grow faster than plain dwelling Indians and are taller and heavier at the age of 19 years. (3) The highlanders exhibit greater chest circumference than the lowland norms. This finding, similar to those among Andean natives, supports high altitude hypoxia's role in human growth and morphology.     

Radioimmunoassay of androsterone and androsterone-3-sulfate in plasma

Details of a sensitive and specific radioimmunoassay for androsterone (1) and androsterone sulfate in plasma have been presented. Benzene extracts of plasma were chromatographed on a lumina to isolate the androsterone fraction either (a) directly after extraction (A) or (b) after solvolysis (AS). Following treatment with rabbit anti-A-17-BSA, antibody bound steroid was precipitated by ammonium sulfate. Androsterone concentrations in normal male plasma averaged 57 ± 24 (S.D.) ng/dl, range 35–135 ng/dl and for normal women, 44 ± 21 (S.D.) ng/dl, range 18–98 ng/dl. Androsterone sulfate concentrations were: males 55 ± 28 μg/dl (range 10–114 μg/dl); premenopausal females 52 ± 31 μg/dl (range 16–318 μg/dl).     

Depression and Altitude: Cross-Sectional Community-Based Study Among Elderly High-Altitude Residents in the Himalayan Regions

Suicide rates are higher at high altitudes, and some hypothesize that hypoxia is the cause. There may be a significant correlation between rates of depression and altitude, but little data exist outside the United States. The purpose of the present study is to conduct a survey of depression among the elderly highlanders in Asia. We enrolled 114 persons aged 60 years or older (mean, 69.2 ± 6.7 years; women, 58.8 %) in Domkhar (altitude, 3800 m), Ladakh, India and 173 ethnic Tibetans (mean, 66.5 ± 6.1 years; women, 61.3 %) in Yushu (altitude, 3700 m), Qinghai Province, China. The two-item Patient Health Questionnaire (PHQ-2) and the geriatric depression scale were administered. A psychiatrist interviewed the subjects who had a positive score on the PHQ-2. The results of the interview with the residents conducted by the specialist showed that two cases (1.8 %) from Domkhar and four (2.3 %) from Qinghai had depression. Despite the high altitude, the probability of depression was low in elderly highlander in Ladakh and Qinghai. Our finding seems to indicate that cultural factors such as religious outlook and social/family relationship inhibit the development of depression.     

Study of the respiratory sensation on high-altitude andeans

The respiratory sensation and some routine cardiorespiratory parameters were studied on native Highlanders from the Argentine Andes and on Lowlanders from Europe, already tested during previous high altitude expeditions. The tests were performed at various altitude levels from 2688m e.i., the village altitude for Highlanders, to 5600m during an expedition to Mt. Aconcagua (6990m). At rest, the perception of 4 external inspiratory resistive loads (ranged between 2.5 and 13 cm.H2O.L-1.s) can allow us to fix by discrimination the sensitivity index P(A) independently of response bias (B) according to Sensory Decision Theory (SDT). The Andean highlanders did not experience the respiratory sensation at the same limits as the European lowlanders well adaptated to high altitude. At higher altitudes than their village altitude, their respiratory sensation presented a lower threshold of perception and a weaker discrimination which might be partly explained by the evolution of some parameters of their cardio-respiratory function when altitude increased. Indeed, in response to high altitude hypoxia (5600m), they increased their respiratory frequency and not their minuteventilation or mouth pressure. This chosen ventilatory pattern was opposite to the one chosen by the Lowlanders and did not allow for sufficient adaptation to a more important altitude hypoxia than that of their village altitude. In conclusion, the Andean highlanders wellbeing adapted to their village altitude, exhibited a difficult acclimatization to higher altitudes which might be due to the characteristics of their respiratory sensation. These results might explain their weak physical performances during ascent to the Mt. Aconcagua summit in spite of special training.     

Assessing population size and structure for Andean Condor Vultur gryphus in Bolivia using a photographic ‘capture‐recapture’ method

The Andean Condor Vultur gryphus is a globally threatened and declining species. Problems of surveying Andean Condor populations using traditional survey methods are particularly acute in Bolivia, largely because only few roosts are known there. However, similar to other vulture species, Andean Condors aggregate at animal carcasses, and are individually recognizable due to unique morphological characteristics (size and shape of male crests and pattern of wing coloration). This provided us with an opportunity to use a capture‐recapture (‘sighting‐resighting’) modelling framework to estimate the size and structure of an Andean Condor population in Bolivia using photographs of individuals taken at observer‐established feeding stations. Between July and December 2014, 28 feeding stations were established in five different zones throughout the eastern Andean region of Bolivia, where perched and flying Andean Condors were photographed. Between one and 57 (mean = 20.2 ± 14.6 sd) Andean Condors were recorded visiting each feeding station and we were able to identify 456 different individuals, comprising 134 adult males, 40 sub‐adult males, 79 juvenile males, 80 adult females, 30 sub‐adult females and 93 juvenile females. Open population capture‐recapture models produced population estimates ranging from 52 ± 14 (se) individuals to 678 ± 269 individuals across the five zones, giving a total of 1388 ± 413 sd individuals, which is roughly 20% of the estimated Andean Condor global population. Future trials of this method need to consider explicitly knowledge of Andean Condor movements and home‐ranges, habitat preferences when selecting suitable sites as feeding stations, juvenile movements and other behaviours. Sighting‐resighting methods have considerable potential to increase the accuracy of surveys of Andean Condors and other bird species with unique individual morphological characteristics.     

Lung volume, chest size, and hematological variation in low-, medium-, and high-altitude central Asian populations

To evaluate adaptive responses to high-altitude environment, we examined three groups of healthy adult males from Central Asia: 94 high-altitude (HA) Kirghiz subjects (3,200 m above sea level); 114 middle-altitude (MA) Kazakh subjects (2,100 m), and 90 low-altitude (LA) Kirghiz subjects (900 m). Data on chest size (chest perimeter and chest diameter), lung volume (forced expiratory volume (FEV) and forced expiratory volume in 1 sec (FEV1)), and hematological parameters (hemoglobin, erythrocytes, hematocrit, and SaO(2)) are discussed. The results show that 1) chest shape is less flat in the samples living at higher altitude. In the HA sample, chest perimeter is lower but chest excursion is high. 2) In the highlanders, forced vital capacity (FVC) and FEV1 are no higher than in the other samples, even when corrected for stature and body weight. The negative correlation between FVC-FEV1 and age decreases with increasing altitude. 3) The HA and MA samples have higher values of hemoglobin, erythrocytes, and hematocrit. The HA sample has lower SaO(2) and higher arterial oxygen content than the LA sample. No association between hematocrit and age was detected in the four samples. The results indicate that the high-altitude Kirghiz present features of developmental acclimatization to hypobaric hypoxia which are also strongly influenced by other major high-altitude environmental stresses.     

Effect of adaptation to high altitude on components of blood and urine of lowlanders compared with high altitude natives

Some of the blood and urinary constituents, oral glucose tolerance and urea clearance were determined in lowlanders at sea level (200 m) and at an altitude of 4, 000 m after their stay of two years. These data were compared with those of natives of high altitude area. The concentration of proteins, cholesterol, creatinephosphokinase and aspartate aminotransferase in blood among lowlanders after 2 year acclimatization were similar to that observed among highlanders. The urinary excretion of creatine and creatinine was of similar magnitude in highlanders and in acclimatized lowlanders but that of 17-keto and 17-hydroxysteroids was higher among highlanders. High altitude acclimatization among lowlanders facilitated appearance of a sharp peak in oral glucose tolerance curves and a decreased fasting blood glucose values. It also induced a restriction in renal filtration as indicated by a depressed urea clearance among lowlanders.     

Major gene for percent of oxygen saturation of arterial hemoglobin in Tibetan highlanders

This report employs a statistical genetic approach to analyze quantitative oxygen transport variables in a high-altitude (4,850–5,450 m) native Tibetan population and demonstrates the presence of a major gene influencing % O₂ saturation of arterial hemoglobin. This result suggests the hypothesis that individuals with the dominant allele for higher % O₂ saturation have a selective advantage at high altitude. Studies of the biologically distinctive Himalayan and Andean populations have greatly influenced thinking about ongoing human evolution and adaptation; this is the first statistical evidence for a major gene enhancing oxygen transport in a highaltitude native population. © 1994 wiley-Liss, Inc.     

High Altitude Hypoxia, Culture, and Human Fecundity/Fertility: A Comparative Study

This paper presents new demographic findings for a high altitude Himalayan population residing in Ladakh, India, and reviews problematic issues regarding the hypothesized relationship between fertility/fecundity and altitude in the Himalayas in light of these findings. It concludes that the low completed fertility ratio reported for the Sherpas of Khumbu, Nepal, is not caused by hypoxia-induced low fecundity, but is the product of cultural factors affecting the exposure of females to the risk of intercourse, a critical confounding factor that has not received adequate consideration in previous studies. Contrary to earlier reports, the present study demonstrates that all high altitude Himalayan populations for which published data exist exhibit moderately high fertility and fecundity, and do not differ significantly in their fertility levels. Furthermore, it argues that the claims for a statistically significant difference in fertility between high, moderate, and low altitude Himalayan populations are groundless, and suggests that a parallel reevaluation of Andean findings is required. [fertility, fecundity, hypoxia, Himalayas, Andes]     

Developmental components of resting ventilation among high- and low-altitude Andean children and adults

This paper evaluates the age-associated changes of resting ventilation of 115 high- and low-altitude Aymara subjects, of whom 61 were from the rural Aymara village of Ventilla situated at an average altitude of 4,200 m and 54 from the rural village of Caranavi situated at an average altitude of 900 m. Comparison of the age patterns of resting ventilation suggests the following conclusions: 1) the resting ventilation (ml/kg/min) of high-altitude natives is markedly higher than that of low-altitude natives; 2) the age decline of ventilation is similar in both lowlanders and highlanders, but the starting point and therefore the age decline are much higher at high altitude; 3) the resting ventilation that characterizes high-altitude Andean natives is developmentally expressed in the same manner as it is at low altitude; and 4) the resting ventilation (ml/kg/min) of Aymara high-altitude natives is between 40–80% lower than that of Tibetans. Am J Phys Anthropol 109:295–301, 1999. © 1999 Wiley-Liss, Inc.     

Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m

Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO(2) (PET(CO(2)), Torr) and end-tidal O(2) (PET(O(2)), Torr), arterial oxygen saturation (Sa(O(2)), %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco (n = 33; 4,300 m) aged 26--62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower PET(O(2)) (48 +/- 4 vs. 53 +/- 2 Torr, P = 0.005) and Sa(O(2)) levels (82 +/- 12 vs. 88 +/- 12%, P < 0.005) and higher PET(CO(2)) (34 +/- 2 vs. 29 +/- 3 Torr, P = 0.005) and Hb concentration (19 +/- 1 vs. 14 +/- 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with PET(CO(2)) and positively correlated with PET(O(2)) and Sa(O(2)). No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle.     

Harris lines in the prehispanic population of Gran Canaria (Canary Islands)

Harris lines were assessed in 194 right tibiae of prehispanic inhabitants of Gran Canaria, belonging to 52 adult females and 123 adult males. No Harris lines were detected in 45 (23%) of the adult individuals (13 females (25%) and 26 males (21%), these differences being not statistically significant. Female tibiae showed a slightly lower mean number of Harris lines at the distal end than male ones (1,692±1.681 in females vs 1.91±1.825 in males). Ages at which Harris lines were formed showed two peaks, a major one at the age of 1 year, and another between 15 and 16 years in males and between 11–12 and 14–15 years in females. Harris lines were more frequently observed at the distal than at the proximal end of the bone. The relative low number of lines detected in our population when compared with the high prevalence of osteoporosis among the adult population of this island is striking.     

Similarity of PO2 and PCO2 values in the air cell of eggs of birds and in the alveolar gas of humans at sea level and at high altitude

At the end of incubation, the partial pressures of oxygen and carbon dioxide in the air cell of sea-level avian eggs are similar to those in the expiratory air of adult birds. At high altitude, changes in the permeability of the shell and probably in the embryo metabolism partially compensates the increase in the gas diffusion constant resulting from the low barometric pressure. The aim of this study was to test whether-despite of the adaptive responses of the high altitude avian embryo-the air cell values would be similar to those of the alveolar air of high altitude human natives. Air cell O₂ (48.3±1.6 torr) and CO₂ (20.9±0.85 torr) pressure values were obtained by studying naturally incubated eggs of the Andean gull (Larus serranus)_at 4650m. Sea-level chicken (Gallus gallus) air cell pressure values of O₂ (102.3±2.7 torr) and of CO₂ (43.3±1.3 torr) were obtained from the literature for comparison. Both these values were similar to those found in the alveolar air of humans at sea level (O₂: 104.4±0.4 torr, CO₂:40.1±0.25 torr) and at high altitude (4540 m) (O₂:50.5±0.53 torr, CO₂: 29.1±0.37 torr). Despite very large evolutionary changes in morphology and physiology of the respiratory organs, the head pressure of O₂ that oxygenates the blood keeps a constant value in the pre-pipping avian embryo and in the alveolar air of adult mammals. This constancy holds valid at high altitude.     

The reproductive status of nonbreeding group members in captive golden lion tamarin social groups

Reproductive activity is limited to only one female in many species of callitrichid primates (marmosets and tamarins): daughters and subordinate females do not produce offspring. A suppression of ovulatory cyclicity is responsible for the lack of reproductive activity in three species of callitrichids studied to date. This study evaluated the endocrine status of golden lion tamarins (Leontopithecus rosalia) housed as daughters or sons in family groups and of individuals housed in isosexual peer groups. Daughters 17 months of age and older and a subordinate female had high levels of estrogen excretion. Mean levels of estrogen excretion in these females were similar to those of nonpregnant, breeding adult females (17.14 ± 6.82 versus 11.93 ± 6.33 μg/mg creatinine, respectively). Estrogen profiles were similar to those of breeding adult females, with sinusoidal cycles in estrogen excretion. Younger daughters in family groups (10 and 12 months old) showed markedly lower levels of estrogen excretion (0.84 ± 0.58 μg/mg creatinine). Estrogen profiles lacked the sinusoidal nature of cycles in older daughters and breeding females, and elevations in estrogen excretion occurred frequently and remained elevated for 1 or 2 days. Plasma testosterone levels in males varied widely, but mean concentrations did not differ among males housed in different social conditions. These results suggest that older daughters and subordinate females may be capable of expressing normal ovarian function in the presence of a breeding adult female. This finding may account for two unusual observations in the lion tamarin: the high level of female-female aggression and the presence of groups in the wild with more than one actively breeding female.     

Bone strontium in pregnant and lactating females from archaeological samples

Because plants and animals consume or absorb different amounts of strontium and calcium, anthropologists are able to use strontium/calcium (Sr/Ca) ratios from archaeologically recovered human bone to estimate the relative contributions of meat and plants to paleodiets. Often females exhibit higher Sr/Ca ratios than males, a fact usually attributed to lower meat intake among women. However, in vivo and in vitro experiments with laboratory animals show that pregnancy and lactation elevate maternal bone strontium and depress maternal bone calcium because 1) strontium is discriminated against in favor of calcium in the transport of ions to the placenta and mammary glands and 2) pregnancy and lactation facilitate absorption of alkaline earth metals from the gut. In this study, bone Sr/Ca ratios and strontium concentrations were compared between reproductive-age females, postmenopausal females, and adult males from two late prehistoric Native American sites in Georgia: the King site (N = 43) and the Etowah site (N = 51). At the King site, the mean Sr/Ca ratio of females was over 14% greater than that of males. At Etowah, the mean strontium level of reproductive-age females exceeded that of postmenopausal females by almost 25%. Most of the difference, it is argued, is due to pregnancy and lactation. A dietary preference among pregnant and lactating women for foods high in alkaline earths, particularly nuts and corn, may also be partially responsible. Until we assess the influence variables other than nutrition exert on trace element concentrations, our reconstructions of paleodiets will be suspect.     

Adaptation and mal-adaptation to ambient hypoxia; Andean, Ethiopian and Himalayan patterns

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of "fitness" for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.