Article

Acid-base balance and weight gain: Are there crucial links via protein and organic acids in understanding obesity?

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Abstract

Obesity is associated with ever increasing social costs posing a general public health challenge. The most obvious reason for obesity, given healthy body functioning, is a positive calorie balance. This article delves into the lesser studied realm of the relationship of weight gain, in particular adipose tissue gain, with increased hydrogen ion concentration, taking protein and organic acids as important caveats in this discussion. The review opens the topic with the contradictory result of various studies reporting a positive relationship between chronic metabolic acidosis and weight loss. It goes to explain a process of weight gain, primarily adipose tissue gain, on acidogenic diets. Insufficient dietary protein could lead to muscle loss, and individual organic acids might indicate if there is any fatty acid oxidation or accumulation of hydrogen ion. The solution to the acid accumulation is discussed not in protein limitation but an increase in the consumption of vegetables and fruits. Finally, this review article based on studies published puts forward a physiological basis including a hypothesis to explain the possible link between hydrogen ion concentration and weight gain. This link could possibly explain the development of diseases and aging partially, and warrants research.

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... The role of nutrition in the induction of insulin resistance has received increasing attention since the recognition of the type 2 diabetes epidemic as a global health crisis by the World Health Organisation [1]. Diet plays a major role in the development of excess body weight, a key risk factor for type 2 diabetes [2]. However, there is also evidence to suggest that diet itself may independently be associated with type 2 diabetes risk [3]. ...
... However, there is also evidence to suggest that diet itself may independently be associated with type 2 diabetes risk [3]. The rapid rise in the prevalence of type 2 diabetes, in combination with earlier disease onset, has led to increased public health concern and a greater focus on the delineation of dietary strategies that may prevent or delay the onset of type 2 diabetes [2]. ...
... The influence of the Western diet on health and disease outcomes in terms of its effect on the body's acid/base balance, has gained increasing interest in recent years [2]. Under normal conditions, blood pH is maintained within a narrow physiological range. ...
Article
Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes.
... Acid-base balance of dietary food consumption has won some recent interest because imbalances in it have been associated with development of the modern-day diseases [1][2][3][4][5]. As a consequence, the physiologic validity of various acid-base indicators, such as the dietary and the anthropometric estimate of organic acid excretion, the dietary unmeasured anion, is in discussion [6,7]. A recent theoretical construct called the net acid excretion capacity (NAEC) has been defined as the residues of net acid excretion (NAE) on urine pH [8] and functions as an index of the kidney's ability to excrete an acid load when measurements of NAE and urine pH are available. ...
... The renal function NAEC was also reported to be lower with aging [8]. A decline in NAEC implies a greater [H+] retention by the body, which when uncorrected can lead to acidosis and probably diseases [5,7]. This hypothesis [7], however, requires to be empirically tested. ...
... A decline in NAEC implies a greater [H+] retention by the body, which when uncorrected can lead to acidosis and probably diseases [5,7]. This hypothesis [7], however, requires to be empirically tested. ...
Article
Acid-base imbalance due to dietary food patterns has emerged as one of the hypotheses leading to modern-day diseases. This study examined if a new method to assess the renal ability to excrete an acid load, that is, the net acid excretion capacity (NAEC), constructed from net acid excretion (NAE) and urine pH, relates to blood hydrogen ion concentration ([H+]) and serum carbon dioxide concentration ([CO2]). In a second analysis, NAE to pH relationship was examined, and is de facto treated to be linear. This study used historical, cross-sectional data of 58 repeated measurements from 8 subjects for the primary measurements of NAEC, blood [H+], and serum [CO2]. Using fixed models, higher NAEC associated with lower [H+] and higher [CO2]. Using hierarchical models, the interindividual variations in [H+] and [CO2] explained the variations in NAEC. In the second analysis (n = 59), a quadratic NAE to pH relationship (NAE = -846.77 + 341.47 pH - 31.50 pH(2)) can be reported. Net acid excretion capacity, a noninvasive tool to assess the renal ability to excrete an acid load, has a physiologic base to it, in that it captures the inherent nonlinear relations of NAE to pH explaining endogenous [H+] retention/excretion. A higher vegetable and fruit consumption might relieve NAEC and allow excess [H+] loss via both renal and respiratory routes.
... The straight line hypothesis of diet, acidosis, diseases-aging (henceforth the straight line hypothesis; SLH) put forward how protons (H+) and their imbalance could relate to obesity [1]. Obesity is known to be caused by many factors: life-style, behavior, metabolism, genetics, etc. [2]. ...
... The SLH highlights hyperventilation and hypoventilation breathing responses [1] principally as it would be important to determine the underlying hypoxia and/or hypercapnia. Erbland and colleagues [28] showed that in normal subjects and patients with chronic obstructive pulmonary disease an increase in respiratory acidosis by increasing carbon dioxide (CO 2 ), greatly potentiated the increase in respiratory drive in response to hypoxia. ...
... The lactic acid construct, called the ''lactic acid trap", would itself be also determined by diet, which could perpetrate a latent to metabolic acidosis [1]. At a lower to higher than normal oxygen intakes; a higher than usual partial oxidation of glucose (glycolysis only) could occur, effecting a lactic acid trap with partial tissue hypoxia under eucapnia to hypercapnia. ...
Article
Studies report on the association between obesity and oxidative stress, with and without additional diseases. Macrophages in adipocytes, and hypoxia in adipose tissue have been suggested to explain how obesity can relate to oxidative stress. The straight line hypothesis using the lactic acid trap construct has been put forward to explain how proton imbalance can relate to obesity. Proton imbalance has been also reported to associate with the production of reactive oxygen species by inhibition of mitochondrial energy production. This review brings together existing literature and concepts to explain how obesity can relate to oxidative stress via protons, uniquely for itself or, as often observed, in conglomeration of additional diseases.
... These reports illustrate the deep and complex relationship between acidogenic diets and serum leptin concentrations in humans. Physiological acidosis may indirectly influence leptin activity through cortisol signaling in obesity which is a condition predicted to be associated with dysregulated acidbase balance [34] . As discussed previously, acid-base status affects cortisol levels [41]. ...
... This dynamic is theorized to inhibit mitochondrial energy production (MEP) through inhibition of the TCA cycle. MEP inhibition results in the diversion of electrons away from completion of the electron transport chain and toward the reduction of oxygen (O 2 ) into reactive oxygen species (ROS) such as free radical oxygen species or peroxides [34,157]. As this cycle continues, vulnerable cells develop a reduced capacity to restore homeostatic balance and are subject to increased intracellular oxidative stress. ...
... Although protein is a major factor involved in promoting endogenous acid production, it should be made clear that attenuation of protein consumption is not a recommended dietary strategy for attaining improved acid-base balance. There is scientific evidence supporting the concept that appropriate alkali supplementation in the form of fruits and vegetables serves aptly to neutralize excess [H + ] produced from protein metabolism [34,194]. The analysis provided discusses how diet-induced acidosis is a potential upstream and indirect trigger in a multifactorial cascade of molecular events associated with carcinogenesis. ...
Article
Full-text available
Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer. Cancer is triggered by genetic and epigenetic perturbations in the normal cell, but it has become clear that microenvironmental and systemic factors exert modifying effects on cancer cell development. While there are no studies showing a direct link between diet-induced acidosis and cancer, acid-base disequilibrium has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence molecular activities at the cellular level that promote carcinogenesis or tumor progression. This review defines the relationship between dietary lifestyle and acid-base balance and discusses the potential consequences of diet-induced acidosis and cancer occurrence or progression.
... A diet with a persistently high acid load can cause blood pH to decrease towards the lower end of the normal physiological range [3]. This disequilibrium in acid/base balance, if not compensated for by homeostatic mechanisms or dietary modification can lead to the development of chronic mild metabolic acidosis [4,5]. The Western diet is characteristically high in animal proteins that when metabolized generate sulfate, a major contributor to dietary acid load [6]. ...
... Long-term consumption of a diet with high acid load can cause blood pH to decrease towards the lower end of the normal physiological range [5]. This diet-induced disruption of the body's acid/base balance has been shown to be associated with increased risk of type 2 diabetes [9]. ...
Article
Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated. Obsen and Obres were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = -0.36, P = 0.03). Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
... Numerous studies show consumption of high-protein foods and insufficient fruit and vegetable intake can increase the body's hydrogen ion load. [16][17][18] These findings suggest that efforts to measure the net acid load from dietary intake may help refine our understanding of the effects of diet on human health. 19,20 Potential renal acid load (PRAL), net endogenous acid production (NEAP) and dietary acid load (DAL) are used to estimate the acidogenic potential of foods and are used as indices to assess dietary acid load. ...
... and otherwise received no points. Also, the ratio of carbohydrate to protein to fat corresponding to (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65): (10)(11)(12)(13)(14)(15): (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) were given six points, ratios of (52-68):(9-16):(13-27) received 4 points, ratios of (50-70):(8-17):(12-30) were given 2 points, and other ratios were given zero points. The total possible DQI-I was 100 points, with higher scores indicating better dietary quality. ...
Article
Introduction: Diet-induced acid load may be associated with overweight and obesity as well as with diet quality. We aimed to study how dietary acid load is associated with overweight, obesity and diet quality indices in healthy women. Methods: We randomly selected 306 healthy 20 to 55 year-old women from health centers affiliated with Tehran University of Medical Science. They were enrolled in a cross-sectional study between June2016 and March 2017. Potential renal acid load (PRAL), net endogenous acid production (NEAP) and dietary acid load (DAL) were calculated for each person. Dietary quality index international (DQI-I),mean adequacy ratio (MAR), and energy density (ED) were estimated. Anthropometry was measured using standard protocols. Nutritional data were obtained from food frequency questionnaires (FFQ). We used multivariable logistic regression models to assess dietary acid load indices in relation to overweight, obesity and abdominal adiposity. Results: Participants had a mean age of 32.4 years. The number and percentage of women who were overweight, obese and who had abdominal obesity were 94(30.7), 38(12.4) and 126(41.2), respectively.The odds of obesity (adjusted odds ratio; Adj. OR = 2.41, 95% confidence interval; CI:1.01-5.74,P = 0.045) and abdominal adiposity (Adj. OR = 2.4, 95% CI:1.34-4.60, P = 0.004) increased significantly with tertile of DAL. Other dietary acid load indices (PRAL and NEAP) showed no significant association with obesity, overweight or abdominal obesity. As dietary acid load scores (PRAL, NEAP and DAL)increased, DQI-I and MAR significantly decreased whereas ED significantly increased across tertilesof dietary acid load indices (P < 0.001). Conclusion: Dietary acid load is associated with obesity and abdominal obesity and is also considered an indicator of diet quality.
... Metabolic acidosis is most commonly assessed by determining the serum bicarbonate ( 2 3 HCO − ) level either by the total carbon dioxide concentration or by arterial blood gases (ABG) using the Henderson-Hasselbach equation with the PH of blood and the partial pressure of carbon dioxide [6]. A good correlation is reported between these measures while another study reported wide differences in findings from the two methods [7] [8]. The differences could however, be as a result of the differences in timing and in sample compartments. ...
... The differences could however, be as a result of the differences in timing and in sample compartments. [8] Locally analyzed samples are reported to give lower bicarbonate values compared with pooled samples assessed in large central laboratories due to gas leakage that results from changes in atmospheric pressure during flights, in addition to sample exposure in larger carriage tubes [9] [10]. ...
... Hunger and forms of under-nutrition has been one of the nutritional research focus, investigating food and/or nutrient shortage and their impact on diseases and survival (Rubin, 2018;Berkemeyer, 2012). Scientific inquiry into over-nutrition has been extremely well-documented, with studies on obesity, metabolic syndrome, diabetes, cancers, and other diseases of civilization (Berkemeyer, 2009). Little though is known about food choice and food perception in the state of being hungry or satiated, a complex of physiological and behavioral processes. ...
... Greater autonomy in food decision-making does not automatically imply healthy food choices (Breer et al., 2017). Further, sanctioned behavior might also present a viable option in nutritional advice with diseases (Berkemeyer, 2009). MacCormack & Lindquist (2019) hypothesized that people experience hunger as emotions and misattribution process (Payne et al., 2010), to demonstrate that hunger (Rubin, 2018;Berkemeyer, 2012) shifts affective perceptions in negative but not in neutral or positive contexts. ...
Conference Paper
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Studies on nutrition have historically concentrated on food-shortages and over-nutrition. The physiological states of feeling hungry or being satiated and its dynamics in food choices, dietary patterns, and nutritional behavior, have not been the focus of many studies. Currently, visual analytic using easy-to-use tooling offers applicability in a wide-range of disciplines. In this interdisciplinary pilot-study we tested a novel visual analytic software to assess dietary patterns and food choices for greater understanding of nutritional behavior when hungry and when satiated. We developed software toolchain and tested the hypotheses that there is no difference between visual search patterns of dishes 1) when hungry and when satiated and 2) in being vegetarian and non-vegetarian. Results indicate that food choices can be deviant from dietary patterns but correlate slightly with dish-gazing. Further, scene perception probably could vary between being hungry and satiated. Understanding the complicated relationship between scene perception and nutritional behavioral patterns and scaling up this pilot-study to a full-study using our introduced software approaches is indispensable.
... In our study, most of the results from the correlation analysis between NEAP and both the anthropometric characteristics and nutrients (Figures 2 and 3) are in close agreement with the findings of the above-mentioned study by Gannon et al,27 as well as with a number of other studies (reviewed in Berkemeyer35). The relationships between NEAP and macro- and micronutrients were to some extent, but not entirely, in accordance with what we initially expected, demonstrating the importance of examining how these nutrients may have an impact on dietary acid load. ...
Article
Full-text available
Dietary intake has been shown to influence the acid-base balance in human subjects; however, this phenomenon is poorly understood and rarely reported for the least well-studied segment of older people in a developing country. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a sample of otherwise healthy elderly aged 50 years and above; and (2) compare NEAP between the elderly and young to determine the effects of aging, which could contribute to changes in the acid-base balance. Analyses were carried out among 526 elderly and 131 young participants (aged 50-80 and 23-28 years, respectively), all of whom were free of discernible disease, nonsmokers, and not on any chronic medication. Selected anthropometric factors were measured and 24-hour dietary recall was recorded. We used two measures to characterize dietary acid load: (1) NEAP estimated as the dietary potential renal acid load plus organic acid excretion, the latter as a multiple of estimated body surface area; and (2) estimated NEAP based on protein and K. For the young and elderly, the ranges of NEAP were 12.1-67.8 mEq/d and 2.0-78.3 mEq/d, respectively. Regardless of the method used, the mean dietary acid-base balance (NEAP) was significantly higher for the elderly than the young (P = 0.0035 for NEAP [elderly, 44.1 mEq/d versus young 40.1 mEq/d]; and P = 0.0035 for the protein:potassium ratio [elderly, 1.4 mEq/d versus young 1.1 mEq/d]). A positive and significant correlation was found between NEAP and energy, protein, and phosphorus (P < 0.05 for all trends). The findings from this study provide evidence of the relatively higher production of NEAP in older people, possibly as an effect of higher consumption of certain acid-producing foods by the elderly.
... Notwithstanding the pseudoscientific extrapolation of the low-grade acidosis proposal into so-called alkaline diets by lay writers, intriguing prospective research has shown that dietary acid load increases subsequent risk of type 2 diabetes [244]. Acid load has also been linked to cardiovascular health [245], elevated body weight, increased waist circumference and a lower percentage of lean body mass [246][247][248]. ...
Article
Full-text available
In 21st-century public health, rapid urbanization and mental health disorders are a growing global concern. The relationship between diet, brain function and the risk of mental disorders has been the subject of intense research in recent years. In this review, we examine some of the potential socioeconomic and environmental challenges detracting from the traditional dietary patterns that might otherwise support positive mental health. In the context of urban expansion, climate change, cultural and technological changes and the global industrialization and ultraprocessing of food, findings related to nutrition and mental health are connected to some of the most pressing issues of our time. The research is also of relevance to matters of biophysiological anthropology. We explore some aspects of a potential evolutionary mismatch between our ancestral past (Paleolithic, Neolithic) and the contemporary nutritional environment. Changes related to dietary acid load, advanced glycation end products and microbiota (via dietary choices and cooking practices) may be of relevance to depression, anxiety and other mental disorders. In particular, the results of emerging studies demonstrate the importance of prenatal and early childhood dietary practices within the developmental origins of health and disease concept. There is still much work to be done before these population studies and their mirrored advances in bench research can provide translation to clinical medicine and public health policy. However, the clear message is that in the midst of a looming global epidemic, we ignore nutrition at our peril.
... After estrogen supplementation, both postmenopausal women and ovariectomized (OVX) rodents show lipogenesis inhibition via the downregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1) and acetyl-CoA carboxylase (ACC) [9,23]. SREBP-1c and PPAR-γ are key transcription factors in the control of both lipogenesis [3] and adipogenesis [27]. PPAR-γ increases the number of small and new adipocytes. ...
Article
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Ovarian hormone loss is associated with a shift in fat distribution to intra-abdomin al adipose tissue (intra-AAT) depots and with lipid metabolism disorders, which predisposes individuals to developing insulin resistance. Resistance training (RT) prevents increases in intra-AAT after ovarian hormone loss. However, the molecular mechanisms underlying these changes remain unclear. We investigated the effects of ovariectomy and RT on gene expression related to lipogenesis and fat oxidation in the intra-AAT of ovariectomized rats. Sprague-Dawley rats (n=6/group) were divided into the groups: sham-sedentary, ovariectomized-sedentary, sham-RT and ovariectomized-RT. RT groups performed a 10-week climbing program on a ladder with progressive overload. Intra-AAT was subjected to morphometric and mRNA analysis. Ovariectomized-sedentary group had larger adipocytes and higher expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), hormone-sensitive lipase (HSL) and lower expression of the oxidative carnitinepalmitoyltransferase-I (CPT-1). RT counteracted OVX-induced increases in PPAR-γ and SCD-1 and decreased SREBP-1c. ACC and HSL were downregulated in ovariectomized-RT compared with the ovariectomized-sedentary group. Ovariectomized-RT group had the highest CPT-1 gene expression. Adipocyte size decreased in ovariectomized-RT group. Results suggest that RT reduces intra-AAT adipocyte size in ovariectomized rats by suppressing intra-AAT fatty acid synthesis and enhancing fatty acid β-oxidation.
... Unmeasured anion accumulation and retention and increased acid synthesis are hallmarks of obesity, and higher BMI has been associated with an increased risk of developing anion gap metabolic acidosis [15,46]. Here, we noticed a strong and direct association be-tween the endogenous production of organic acid anions (OA), BMI, and body fat, and TKV, despite adjusting for potential confounders such as age, sex, presence of hypertension, and baseline measured eGFR, in the multivariate analysis. ...
Article
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Background and Objectives: A high body mass index (BMI) is associated with the progression of autosomal dominant polycystic kidney disease (ADPKD). However, body fat (BF), which is another adiposity marker, has not yet been studied. Excessive weight may promote elevationin the endogenous synthesis of organic acid (OA) anions. Accordingly, we aimed to investigate the possible association of the aforementioned markers with kidney volume and renal function in patients with ADPKD. Materials and Methods: We conducted a retrospective cohort study of adult ADPKD outpatients involving clinical, serum, and urinary laboratorial data and body composition assessments retrieved from their medical records. BF was estimated by skinfold thickness (mm) on the non-dominant arm and was considered as normal or high for each sex. Total kidney volume (TKV) and height-adjusted volume (htTKV) were measured by magnetic resonance imaging. The annual estimated glomerular filtration rate (eGFR) slope was analyzed during a median follow-up time of 6 (5.0–7.0) years to calculate rapid progression (decline in renal function �2.5 mL/min/year over 5 years). Results: A total of 104 patients were included (41.9 � 11.9 years old, 38.5% men), with 62.5% of the patients classified as high BF. The High BF group presented higher levels of OA, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), 24 h urinary sodium (UNa), and htTKV, and lower eGFR than those with a normal BF. In the multivariate linear regression, the associated variables with TKV were high BF, OA and BMI (std. � 0.47, p < 0.05; std. � 0.36, p = 0.001; std. � 0.25, p = 0.01, respectively). In the binary logistic regression, when adjusted for potential confounders, UNa was the only parameter associated with an increased risk of eGFR decline �2.5 mL/min/year (OR 1.02, 95% CI 1.01–1.03, p = 0.02). Conclusions: Increased body fat and endogenous production of organic acid anions are associated with larger kidney size in ADPKD but not with a decline in renal function.
... Acidosis is known to inhibit mitochondrial energy production (4,5), whereby it has been proposed that the electrons could be free for production of reactive oxygen species (ROS) (3)(4)(5). The present study provides some support toward this proposition. ...
... Previous studies have identified pathways linking PRAL and CVD risk. These may possibly relate to the role of dietÕs acidity in increasing blood pressure or hypertension risk (17,18,30) or indirectly affecting other CVD risk factors such as hypercholesterolemia, increased body weight or waist circumferences, increased insulin resistance, diabetes (19,(31)(32)(33), or osteoporosis (22,23,34). Compared with the preindustrial period, humans today have a diet poor in magnesium, potassium, and fiber but rich in saturated fat, sugar, sodium, and chloride (3). ...
Article
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Background: Conflicting evidence associates diet acidity with the incidence of chronic diseases such as hypertension, diabetes, kidney disease, and bone-mineral disorders. It is currently unknown whether dietary acidity is associated with death. Objective: We investigated the association of dietary acid load with the risk of all-cause and cardiovascular disease (CVD) mortality. Methods: We used data from 2 prospective cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men, which included 36,740 women and 44,957 men aged 45-84 y at the start of a 15-y follow-up period (1998-2012). Acid load was estimated from food-frequency questionnaires by use of the validated potential renal acid load (PRAL) algorithm. Deaths were ascertained via record linkage. Associations of PRAL with mortality were modeled by use of restricted cubic splines. Results: The median PRAL was 0.65 mEq/d (range: -109 to 81.5 mEq/d) in women and 12.3 mEq/d (-111 to 121 mEq/d) in men. During a mean of 13.5 ± 3.3 y of follow-up, there were 8576 and 13,332 deaths, of which 3203 and 5427 were attributed to cardiovascular causes in woman and men, respectively. In both sexes, a nonlinear U-shaped relation was observed, with higher mortality rates for both dietary acid and alkali excess. Compared with neutral PRAL (0 mEq/d), the HRs for all-cause mortality for the 10th and 90th percentiles of PRAL were 1.05 (95% CI: 1.01, 1.10) and 1.03 (95% CI: 0.98, 1.08), respectively, in women. The corresponding results for men were HRs 1.01 (95% CI: 1.00, 1.02) and 1.04 (95% CI: 1.00, 1.08) respectively. This relation was slightly stronger for CVD mortality. Conclusions: Excess diet alkalinity and acidity both showed weak associations with higher mortality in Swedish adults. An acid-base balanced diet was associated with the lowest mortality, but the magnitude of mortality reduction was modest. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698 The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711.
... Another factor known to influence physiological acid-base systems is the dietary acid load. 1 The ratio of diet-derived fixed acid to base is estimated by the potential renal acid load (PRAL), and when endogenously produced organic acid is factored, cumulatively, this determines the net endogenous acid production (NEAP) for an individual. 1 When diet chronically releases fixed acid in excess of fixed base, the surplus acid has been hypothesised to be a contributing factor to chronic disease. 2,3 While an elevated (acid) NEAP does not result in clinical metabolic acidosis, 4 research is being conducted to determine its relationship to sarcopenia, 5,6 gout, 7,8 renal stones, 9,10 metabolic syndrome, 11 chronic renal insufficiency, 12 late metabolic acidosis in preterm infants, 13 hypertension, 14,15 insulin resistance, 16,17 non-alcoholic fatty liver disease, 18 impaired sports performance 19,20 and osteoporosis, 21,22 while the involvement of NEAP in obesity 23 and cancer 4 has been theorised. ...
Article
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Aim: The gold standard of measurement for net endogenous acid production (NEAP) is net acid excretion (NAE), a test that is not readily available, and consequently, estimative equations by Remer and Manz and Frassetto et al. are often used. These equations rely on nutrient databases and it is recommended that their validity be assessed using a country's database before their application in research in that country. We sought to delineate the accuracy and precision of these estimation equations using the Australian food database. Methods: In a double blind, randomised, cross-over fashion, healthy participants (n = 13) residing in regional Australia were exposed to varying net acid loads while they collected weighted food diaries and 24-hour urine samples for measurement of NAE. Results: In comparison to the Frassetto et al. equations (equation one bias = -57.1 mEq/day, equation two bias = -32.8 mEq/day), only the Remer and Manz equation was accurate (bias = -5.4 mEq/day); however, all equations were imprecise. Conclusions: Using the Australian database, the performance of these equations to predict NEAP appears equal to other databases; however, caveats apply in their application. For future research, the equation by Remer and Manz is preferential for group estimates. None of the equations are recommended for individual estimates.
... Based on these findings, it has been suggested that adherence to a low PRAL ("alkaline") diet or consumption of an alkaline supplement to offset the acid load of a meal may be used to improve glucose metabolism in at-risk individuals [16]. However, to have a chronic effect on glucose metabolism, the alkalizing effect of a low PRAL diet may, or may not, be mediated by acute (that is, immediately post-meal) mechanisms, relating to insulin secretion. ...
Article
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Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants (n = 32) were randomized to receive either 1680 mg NaHCO3 or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1–4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C-peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15–30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo (p = 0.001), but not with NaHCO3 (p = 0.86) and remained decreased with the placebo for 3 h (pinteraction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO3 compared with placebo (p = 0.02). However, postprandial glucose, insulin, C-peptide, NEFA and GLP-1 were not different between treatments (pinteraction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.
... Obesity is associated with impaired acid-base balance; obesity lead to higher urinary calcium excretion and reduced urinary pH [8]. It has also been suggested that hydrogen ion accumulation due to acidogenic diets is associated with increased weight gain and obesity and that possibly meat and western diet is a cause of increased organic acid production and fatty acid oxidation in obese individuals; a condition which might be reversed in higher vegetables and fruits consumption [9]. High acidogenic contents of foods including meat, fish, cheese and lower alkaline content of diet including fruits and vegetables are the potential cause of endogenous acid production and elevated dietary acid load [10]. ...
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Background In the current meta-analysis, we aimed to systematically review and summarize the eligible studies evaluating the association between dietary acid load in terms of potential renal acid load (PRAL) and net-endogenous acid production (NEAP) with anthropometric parameters and serum lipids in adult population. Methods In a systematic search from PubMed, Scopus, Web of Sciences and Cochrane electronic databases up to December 2018, relevant studies were included. Cross-sectional, case control or cohort studies evaluating the association between PRAL and NEAP with the mean values of body mass index (BMI), waist circumference (WC), low and high density lipoprotein cholesterol (LDL, HDL), triglyceride (TG), total cholesterol (TC) and the prevalence of obesity were included. Results According to our results, having higher dietary acid load content in terms of high PRAL scores was associated with higher triglyceride concentrations (weighted mean difference (WMD): 3.468; confidence interval (CI): -0.231, 7.166, P = 0.04) and higher obesity prevalence (30% and 27% in highest versus lowest categories). Accordingly, being in the highest category of NEAP was associated with higher prevalence of obesity (25% and 22% in highest versus lowest category). In subgroup analysis, higher PRAL scores was associated with higher BMI in women (WMD: 0.122; CI: -0.001, 0.245; P = 0.049) and higher NEAP in men (WMD: 0.890; CI: 0.430, 1.350; P < 0.001). There was no association between dietary acid load and other studied parameters. Conclusions In the current meta-analysis, high dietary acid load content was associated with higher serum triglyceride concentrations and higher obesity prevalence. Reducing dietary acid load content might be a useful preventive strategy against obesity and metabolic disorders.
... In the current study we examined the role of DAL in prediction of survival and our results revealed that high PRAL scores could be considered as a positive predictor of mortality in patients underwent CABG. Several studies suggested the increased risk of CVD in higher PRAL score possibly due to increased insulin resistance, blood pressure, adiposity and incidence of diabetes or hypertension [17][18][19][20][21]34,35]. Former studies have shown, individuals with higher dietary acid load have a tendency to unhealthy lifestyle patterns, including higher BMI, sedentary life-style and great interest to western diet patterns [18,21]. ...
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Backgrounds Numerous studies have revealed the role of dietary acid load as a potential risk factor for cardiovascular events and blood pressure. However, its role in predicting the mortality rate in patients underwent coronary artery bypass grafting surgery (CABG) has not been reported. In the current study we aimed to evaluate the relationship of dietary acid load and cardio-metabolic risk factors with ten year survival among patients underwent CABG. Methods The current prospective cohort study comprises 454 patients underwent CABG. Anthropometric, clinical and biochemical measurements were performed. Dietary acid load was calculated as either potential renal acid load (PRAL) or net endogenous acid production (NEPA) using the data obtained from a semi-quantitative food frequency questionnaire (FFQ). Survival analysis was performed using Kaplan-Meier method followed by log-rank test. The association between all-cause mortality and study parameters was performed with Cox-proportional hazard model. Results Patients in the higher PRAL and NEAP quartiles had lower BMI and lower ejection fraction rate (P <0.05). Moreover, lower hematocrit values were observed in patients of higher PRAL quartiles. Higher PRAL scores were associated with higher mortality rate and reduced survival days (adjusted hazard ratio: 1.023 (1.00–1.04; P-value = 0.01). However, there was no relationship between NEAP and survival. Conclusions We revealed that high PRAL scores are positive predictors of 10-year mortality in patients underwent CABG. The results of our study suggest that maintaining an adequate acid-base balance can contribute to longevity by reducing the risk of mortality.
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In 64 apparently healthy adult humans (ages 17-74 yr) ingesting controlled diets, we investigated the separate and combined effects of age, glomerular filtration rate (GFR, index of age-related renal functional decline), renal net acid excretion [NAE, index of endogenous acid production (EAP)], and blood PCO2 (PbCO2, index of respiratory set point) on steady-state blood hydrogen ion ([H+]b) and plasma bicarbonate concentration ([HCO3-]p). Independent predictors of [H+]b and [HCO3-]p were PbCO2, NAE, and either age or GFR, but not both, because the two were highly correlated (inversely). [H+]b increased with increasing PbCO2, NAE, and age and with decreasing GFR. [HCO3-]p decreased with increasing NAE and age but increased with increasing PbCO2 and GFR. Age (or GFR) at constant NAE had greater effect on both [H+]b and [HCO3-]p than did NAE at constant age (or GFR). Neither PbCO2 nor NAE correlated with age or GFR. Thus two metabolic factors, diet-dependent EAP and age (or GFR), operate independently to determine blood acid-base composition in adult humans. Otherwise healthy adults manifest a low-grade diet-dependent metabolic acidosis, the severity of which increases with age at constant EAP, apparently due in part to the normal age-related decline of renal function.
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Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g. sodium-hydrogen exchange, NHE) may predict the subset of diabetic patients for whom intensive modalities of treatment are indicated despite their potential risk. However, the accuracy of NHE as a marker of microangiopathy has not been assessed. In this study NHE as initial velocity of amiloride-inhibited H+ efflux from erythrocytes (pHi 6.35-6.45) into an Na(+)-containing medium (pHo 7.95-8.05), was estimated during 8 years of follow-up in 138 non-microalbuminuric diabetic patients (74 women, 64 men, age 52 +/- 4 years) treated with antihyperglycaemic drugs for 14 +/- 2 years. Appearance of microalbuminuria, overt proteinuria, azotaemia and retinopathy was assessed annually. Enhanced erythrocyte NHE predicted diabetic nephropathy alone and in association with a family history of hypertension and/or nephropathy with a sensitivity of 86 and 93%, respectively. No association was found between NHE and retinopathy in NIDDM. It is concluded that assessment of erythrocyte NHE can identify a subset of patients likely to develop renal damage, for whom an aggressive treatment approach might be considered.
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Proton pumping across the mitochondrial inner membrane and proton leak back through the natural proton conductance pathway make up a futile cycle that dissipates redox energy. We measured respiration and average mitochondrial membrane potential in perfused rat hindquarter with maximal tetanic contraction of the left gastrocnemius-soleus-plantaris muscle group, and we estimate that the mitochondrial proton cycle accounted for 34% of the respiration rate of the preparation. Similar measurements in rat hepatocytes given substrates to cause a high rate of gluconeogenesis and ureagenesis showed that the proton cycle accounted for 22% of the respiration rate of these cells. Combining these in vitro values with literature values for the contribution of skeletal muscle and liver to standard metabolic rate (SMR), we calculate that the proton cycle in working muscle and liver may account for 15% of SMR in vivo. Although this value is less than the 20% of SMR we calculated previously using data from resting skeletal muscle and hepatocytes, it is still large, and we conclude that the futile proton cycle is a major contributor to SMR.
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Hip fracture, a major health problem in elderly persons, varies in incidence among the populations of different countries and is directly related to animal protein intake, a finding that suggests that bone integrity is compromised by endogenous acid production consequent to the metabolism of animal proteins. If that is so, vegetable foods might provide a countervailing effect, because they are a rich source of base (bicarbonate) in the form of metabolizable organic anions, which can neutralize protein-derived acid and supply substrate (carbonate) for bone formation. We analyzed reported hip fracture incidence (HFI) data among countries (N = 33) in women aged 50 years and older, in relation to corresponding country-specific data on per capita consumption of vegetable and animal foods as reported by the United Nations Food and Agriculture Organization. HFI varied directly with total (r = +.67, p < .001) and animal (r = +.82, p < .001) protein intake and inversely with vegetable protein intake (r = .37, p < .04). The countries in the lowest tertile of HFI (n = 11) had the lowest animal protein consumption, and invariably, vegetable protein (VP) consumption exceeded the country's corresponding intake of animal protein (AP): VP/AP > 1.0. By contrast, among the countries in the highest tertile of HFI, animal protein intake exceeded vegetable protein intake in nearly every case (10 of 11 countries). Among all countries, HFI correlated inversely and exponentially with the ratio of vegetable/animal protein intake (r = -.84, p < .001) and accounted for 70% of the total variation in HFI. Adjusted for total protein intake, vegetable food consumption was an independent negative predictor of HFI. All findings were similar for the subset of 23 countries whose populations are predominantly Caucasian. The findings suggest that the critical determinant of hip fracture risk in relation to the acid-base effects of diet is the net load of acid in the diet, when the intake of both acid and base precursors is considered. Moderation of animal food consumption and an increased ratio of vegetable/animal food consumption may confer a protective effect.
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Background: Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. Objective: We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. Design: This was a prospective cohort study with a mean (±SD) of 7.0 ± 1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Results: Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Conclusions: Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.
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It is the position of the American Dietetic Association that children ages 2 to 11 years should achieve optimal physical and cognitive development, attain a healthy weight, enjoy food, and reduce the risk of chronic disease through appropriate eating habits and participation in regular physical activity. The health status of American children has generally improved during the past 3 decades. However, the number of children who are overweight has more than doubled among 2- to 5-year-old children and more than tripled among 6- to 11-year-old children, which has major health consequences. This increase in childhood overweight has broadened the focus of dietary guidance to address children's overconsumption of energy-dense, nutrient-poor foods and beverages and physical activity patterns. Health promotion will help reduce diet-related risks of chronic degenerative diseases, such as cardiovascular disease, type 2 diabetes, cancer, obesity, and osteoporosis. This position reviews what US children are eating and explores trends in food and nutrient intakes as well as the impact of school meals on children's diets. Dietary recommendations and guidelines and the benefits of physical activity are also discussed. The roles of parents and caregivers in influencing the development of healthful eating behaviors are highlighted. Specific recommendations and sources of nutrition messages to improve the nutritional well-being of children are provided for food and nutrition professionals
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The prevalence of diabetes mellitus is increasing world-wide, even if it varies markedly in the geographical areas and populations investigated. This study is part of the Progetto Finalizzato Invecchiamento (Aging Project) of the Italian NCR (National Research Council) and is aimed at investigating the prevalence of diabetes and selected clinical characteristics in a study sample aged between 65 and 84 years of age resident in Catania (Italy). The prevalence rate for type II diabetes was 22.8% and it is certainly among the highest values recorded to date in other areas of Italy and abroad. We distinguished between two forms of diabetes in subjects >70 years of age: aged diabetes with onset in middle age (AD); and diabetes of senescence with onset after 70 years of age (DS). Prevalence rate was 18% for AD and 4.8% for DS, respectively. The age-specific rates of AD and DS show the progressive lower prevalence rates of the former and the higher rates of the latter. We assume that DS is mainly caused by atherosclerotic processes and represents the typical form of diabetes in the elderly.
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This study was performed to test the hypothesis that potassium concentration in arterialized blood may be closely related to maximal pulmonary ventilation (V.Emax) obtained at exhaustion during maximal exercise in man. Eleven healthy men performed bicycle exercise with incremental loading at 60 rpm until exhaustion. Pulmonary ventilation (V.E), oxygen uptake (V.O2), and heart rate (HR) were determined continuously throughout the experiment. Arterialized venous blood samples were collected to measure potassium ([K+]), lactate ([La]), hydrogen ion (pH), catecholamine ([CA]), and dopamine ([DA]) concentrations. A significant correlation (r = 0.98-0.88) between V.E and [K+], [La], and pH during exercise was observed in all subjects. Furthermore, a close relationship was found in this study between dopamine concentration measured at exhaustion ([DA]0) and maximal pulmonary ventilation per kilogram of body weight (V.Emax/W) (r = -0.668, p < 0.05) or maximum oxygen uptake per kilogram of body weight (VO2MAX/W) (r = 0.720, p < 0.05). However, no significant correlation was found between V. Emax/W and [K+]0 (r = 0.202, NS), [La]0 (r = -0.096, NS), and pH0 (r = 0.344, NS). These results suggest that dopamine may play a more important role in the determination of maximal pulmonary ventilation during exercise in man than K+ or pH.
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Diss. med. Basel. Literaturverz. Sonderdr. aus: American journal of physiology. Renal physiology ; 284, 2003.
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To evaluate whether renal net acid excretion capacity (NAEC) varies across different age groups and, specifically, whether it falls in elderly people. Cross-sectional observational study. Community-based. Young participants were from the DOrtmund Nutritional and Anthropometric Longitudinally Designed Study, Dortmund, Germany; elderly participants were from Gothenburg, Sweden. Twenty-four-hour urine pH, net acid excretion (NAE), urinary phosphorus, total nitrogen excretion, and anthropometric data were measured in healthy elderly people (aged 55-75; n=85), young adults (aged 18-22; n=117), adolescents (aged 13-14; n=112), and prepubescent children (aged 6-7; n=217). NAEC was determined as 24-hour NAE adjusted for urine pH using the residual method. In elderly participants 24-hour urinary pH (5.9+/-0.53) was lower (P<.05) and NAE (60+/-27 mEq/d) higher (P<.05) than in the three other groups. In a regression model adjusted for age, sex, and body surface area, NAEC showed a clear decrease with age, with highest values in prepubescents and lowest in elderly participants. However, NAEC remained significantly lower only in elderly participants (P<.001) after the inclusion of total nitrogen excretion, a protein intake index, which was included because protein intake is known to modulate renal function. NAEC was approximately 8 mEq/d lower in healthy elderly participants than in young adults. The capacity to excrete net endogenous acid does not vary markedly from childhood to young adulthood but falls significantly with age, implying that elderly people may require higher daily alkalizing mineral intake to compensate for renal function losses.
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Waist circumference has been shown to be a better predictor of cardiovascular risk than body mass index (BMI). Our case-control study aimed to evaluate the contribution of obesity and abdominal fat mass to the risk of stroke and transient ischemic attacks (TIA). We recruited 1137 participants: 379 cases with stroke/TIA and 758 regional controls matched for age and sex. Associations between different markers of obesity (BMI, waist-to-hip ratio, waist circumference and waist-to-stature ratio) and risk of stroke/TIA were assessed by using conditional logistic regression adjusted for other risk factors. BMI showed a positive association with cerebrovascular risk which became nonsignificant after adjustment for physical inactivity, smoking, hypertension, and diabetes (odds ratio 1.18; 95% CI, 0.77 to 1.79, top tertile versus bottom tertile). Markers of abdominal adiposity were strongly associated with the risk of stroke/TIA. For the waist-to-hip ratio, adjusted odds ratios for every successive tertile were greater than that of the previous one (2nd tertile: 2.78, 1.57 to 4.91; 3rd tertile: 7.69, 4.53 to 13.03). Significant associations with the risk of stroke/TIA were also found for waist circumference and waist-to-stature ratio (odds ratio 4.25, 2.65 to 6.84 and odds ratio 4.67, 2.82 to 7.73, top versus bottom tertile after risk adjustment, respectively). Markers of abdominal adiposity showed a graded and significant association with risk of stroke/TIA, independent of other vascular risk factors. Waist circumference and related ratios can better predict cerebrovascular events than BMI.
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1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of V̇o2 max. on three occasions when NH4Cl, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+])weremeasured at frequent intervals. 2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% V̇o2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4Cl. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4Cl caused a variable elevation of HGH at rest and 33% V̇o2 max. At 66% V̇o2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% V̇o2 max., HGH was highest with NaHCO3. 4. An infusion of sodium l(+)-lactate producing plasma lactate concentrations of 3–5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.
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The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise.
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Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.
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In 11 infants (birth weight greater than 1800 g) fed a new type of humanized formula with a low phosphorus (P) content (calcium (Ca) 11 mmol/l, P 7.2 mmol/l, sodium (Na) 8.3 mmol/l) biochemical parameters of blood, serum and urine were determined. In nine boys Ca and P balances were evaluated also. Renal net acid excretion was low (0.85 mmol/kg/day). Mean concentrations of P and Ca in urine were 0.34 mmol/kg/day (10.5 mg/kg/day) and 0.1 mmol/kg/day (4 mg/kg/day), respectively. In four infants, Ca concentration in urine was, however, greater than 0.15 mmol/kg/day) (6 mg/kg/day). In infants with birth weights greater than 1800 g fed the new, low-P formula, the low renal net acid excretion, the normal P and the high Ca concentrations in urine were comparable to term infants fed human milk. The high calciuria in several infants may be normal physiologic values. However, it remains to be established that the urinary solubility product of infants fed the new, low-P formula is in the same range as those for infants fed human milk. Unexpectedly, low urinary Na excretion (0.26 mmol/kg/day) and increased urinary excretion of aldosterone-18-glucuronide indicated biochemical evidence of Na deficiency secondary to low Na intake and a high weight gain. If the new, low-P formula is to be fed to infants with a birth weight as low as 1800 g. Na content should be higher than in mature human milk because of the often relatively higher weight gain.
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There is evidence that the cytosolic free Ca2+, protein kinase C, and the Na(+)-H+ antiport cross-communicate with one another through positive and negative feedback mechanisms, thereby maintaining cellular Ca2+ and pH homeostasis. This triumvirate may play a role in the development of insulin resistance--a common characteristic of both essential hypertension and non-insulin-dependent diabetes mellitus. Circulating cells from patients with essential hypertension and non-insulin-dependent diabetes mellitus demonstrate elevated cytosolic free Ca2+, increased protein kinase C activity, or both, and these perturbations are associated with augmented activity of the Na(+)-H+ antiport. If present in other cells (e.g., striated muscle cells and adipocytes), these alterations could underlie insulin resistance in essential hypertension and non-insulin-dependent diabetes mellitus.
Article
We have investigated the cellular basis for the clinical and epidemiologic linkage of hypertension, left ventricular hypertrophy (LVH), obesity, and non-insulin-dependent diabetes mellitus (NIDDM) and have studied cytosolic free calcium and free magnesium levels in these syndromes. Specifically, intracellular free calcium is elevated and free magnesium is deficient in hypertension, and both are related (directly and inversely, respectively) to the ambient level of blood pressure, to LV mass index (and thus to the degree of cardiac hypertrophy), and to the hyperinsulinemia and insulin resistance of essential hypertension. Dynamically, the ability of dietary salt loading to elevate blood pressure corresponds to its ability to elevate cytosolic free calcium and reciprocally to suppress free magnesium levels. Conversely, the ability of calcium channel blockade to reverse salt-induced hypertension is related to its ability to prevent these transmembrane ionic effects. Higher steady-state free calcium or lower free magnesium, or both, are also observed in clinical states linked to hypertension, such as obesity and NIDDM. Oral glucose loading in normal subjects itself elevates free calcium and suppresses free magnesium levels, as does hyperglycemia in vitro.
Article
Metabolic acidosis is associated with increased calciuria and ammoniagenesis. This study evaluated the effects of oral sodium bicarbonate (NaHCO3) or combined potassium bicarbonate-calcium carbonate supplementation on urinary mineral excretion during the ketoacidosis of a very-low-energy protein diet. Seventeen healthy obese subjects (BMI: 37.5 +/- 3.2 kg/m2, weight: 100 +/- 3 kg) were given a 1.72 MJ all protein (93 g) liquid formula and a multivitamin-mineral supplement daily for 3 weeks. Subjects in groups 1 (n = 6) and 2 (n = 5) received 16 mmol KCl. In addition, subjects in group 1 received 60 mmol Na+ daily as sodium chloride, subjects in group 2, 60 mmol Na+ as NaHCO3. The subjects in group 3 (n = 6) were given 32 mmol K+ as bicarbonate and 16 mmol Ca++ as carbonate daily. Metabolic acidosis was prevented in groups 2 and 3 with bicarbonate and bicarbonate-carbonate administration. This was reflected in significant curtailment of the augmented ammonium nitrogen excretion found in group 1. The additional oral K+ in group 3 improved K+ balance and probably also inhibited ammoniagenesis. Urine calcium was greater (p less than 0.04) in group 1 subjects, but similar in groups 2 and 3, despite higher calcium intake in group 3. Urinary phosphorus decreased with time in all groups, but more so in the group 2 subjects who received NaHCO3. Acidosis was associated with the reverse effect on urinary magnesium, which decreased in group 1 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.
Article
To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHi), free magnesium (Mgi), and cytosolic free calcium (Cai) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Cai, 25.2 +/- 1.4 nM; Mgi, 232 +/- 8 microM), Cai was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mgi was concomitantly suppressed (normotensive: 206 +/- 11 microM, sig = 0.05; hypertensive: 196 +/- 8 microM, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pHi were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Cai and diastolic blood pressure (r = 0.649, p less than 0.001) and body mass index (r = 0.565, p less than 0.001), between Mgi and diastolic blood pressure (r = -0.563, p less than 0.001) and fasting blood glucose (r = -0.580, p less than 0.001), and in diabetics, between pHi and diastolic blood pressure (r = -0.680, p less than 0.001). Thus, the constellation of elevated Cai and suppressed Mgi and pHi levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.
Article
In 14 very-low-birth-weight infants appropriate for gestational age the serum concentrations of urea and the excretions of urea and ammonium in the urine were studied on the 10th, 21st, and 42nd day of postnatal life. All infants were fed with a human milk preparation (6 g human milk lyophilisate per 100 ml fresh human milk). The enteral feeding could be started on the first day of life so that protein intakes were not different on the three study days (2.94 vs. 2.98 vs 3.13 g/kg.d). The renal excretion of urea increased significantly from the 10th to the 42nd day of life (1.2 +/- 0.13 vs 2.1 +/- 0.24 mmol/kg.d) whereas the excretion of ammonium decreased during the same time (0.53 +/- 0.06 vs 0.29 +/- 0.05 mmol/kg.d). There was a significantly negative correlation between the excretion of urea and of ammonia on all study days. The weight gain was sufficient for the given protein intakes (18.9 +/- 3.4 g/kg.d). The results indicate a transient limited capacity of the urea synthesizing system in the liver of very-low-birth-weight infants during the first weeks of life which should be considered if metabolic responses to protein intake are studied and evaluated in these infants.
Article
When our neonatal unit opened in 1984 our formula feeding policy for moderately preterm babies was for casein-predominant rather than "humanized" whey-predominant milk formulae to be given. However, an early cluster of cases of late persistent metabolic acidosis prompted an investigation into the acid-base status and weight gain in preterm infants. This study of 70 healthy, moderately preterm (32-35 weeks) Chinese babies has convincingly shown that a casein-predominant low protein formula is associated with significant metabolic acidosis, persisting sometimes for as long as 8 weeks, and poor weight gain when compared with infants fed on either a humanized or a special low-birthweight formula. This is an important message for the many neonatal units in developing countries where the cost of humanized formulae might initially seem prohibitive, encouraging instead casein-predominant formulae when breast milk is not available. Any additional expense incurred in using humanized formulae will be compensated for by the shortened time spent in hospital.
Article
We have determined the relationship between rate of respiration and protonmotive force in oligomycin-inhibited liver mitochondria isolated from euthyroid, hypothyroid and hyperthyroid rats. Respiration rate was titrated with the respiratory-chain inhibitor malonate. At any given respiration rate mitochondria isolated from hypothyroid rats had a protonmotive force greater than mitochondria isolated from euthyroid controls, and mitochondria isolated from hyperthyroid rats had a protonmotive force less than mitochondria isolated from euthyroid controls. In the absence of malonate mitochondrial respiration rate increased in the order hypothyroid less than euthyroid less than hyperthyroid, while protonmotive force increased in the order hyperthyroid less than euthyroid less than hypothyroid. These findings are consistent with a thyroid-hormone-induced increase in the proton conductance of the inner mitochondrial membrane or a decrease in the H+/O ratio of the respiratory chain at any given protonmotive force. Thus the altered proton conductance or H+/O ratio of mitochondria isolated from rats of different thyroid hormone status controls the respiration rate required to balance the backflow of protons across the inner mitochondrial membrane. We discuss the possible relevance of these findings to the control of state 3 and state 4 respiration by thyroid hormone.
Five healthy male subjects exercised for 3 min at a workload equivalent to 100% VO2max on two separate occasions. Each exercise test was performed on an electrically braked cycle ergometer after a four-day period of dietary manipulation. During each of these periods subjects consumed either a low carbohydrate (3 +/- 0%, mean +/- SD), high fat (73 +/- 2%), high protein (24 +/- 3%) diet (FP) or a high carbohydrate (82 +/- 1%), low fat (8 +/- 1%) low protein (10 +/- 1%) diet (CHO). The diets were isoenergetic and were assigned in a randomised manner. Muscle biopsy samples (Vastus lateralis) were taken at rest prior to dietary manipulation, immediately prior to exercise and immediately post-exercise for measurement of pH, glycogen, glucose 6-phosphate, fructose 1,6-diphosphate, triose phosphates, lactate and glutamine content. Blood acid-base status and selected metabolites were measured in arterialised venous samples at rest prior to dietary manipulation, immediately prior to exercise and at pre-determined intervals during the post-exercise period. There was no differences between the two treatments in blood acid-base status at rest prior to dietary manipulation; immediately prior to exercise plasma pH (p less than 0.01), blood PCO2 (p less than 0.01), plasma bicarbonate (p less than 0.001) and blood base-excess (p less than 0.001) values were all lower on the FP treatment. There were no major differences in blood acid-base variables between the two diets during the post-exercise period.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Plasma cortisol levels were measured in 13 children with marasmus, in 7 with kwashiorkor, and in 24 normal children. Cortisol levels in the malnourished children did not differ from those of the normal group, either before or after 15 or 30 days of treatment, unless there was superimposed acute stress. Stress caused by complications such as hypoglycaemia, infection, hypothermia, or acidosis led to raised plasma cortisol levels.
Article
Starvation entails a progressive selection of fat as body fuel. Soon after a meal glucose utilisation by muscle ceases and fatty acids are used instead. Ketoacid levels in blood become elevated over the first week, and the brain preferentially uses these instead of glucose. The net effect is to spare protein even further, as glucose utilisation by brain is diminished. Nevertheless, there is still net negative nitrogen balance, but this can be nullified by amino acid or protein supplementation. Insulin appears to be the principal regulatory hormone. Recent data suggest that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs.
Article
Four obese women, each at least 50% above their expected weight for height were maintained in the metabolic unit for 63 days on liquid formula diets of differing protein and calorie content. We made the following findings: 1) When 12 g protein nitrogen was consumed, 1 mEq of acid was excreted in the urine for every 2 mEq of urinary sulphate. 2) On a protein-free diet more acid was excreted in the urine than could be accounted for by oxidation of sulphur to the sulphate which was excreted in the urine. 3) Both increased consumption of protein and a restriction of dietary calories was associated with an increase of urinary acid. 4) Urinary sulphur excretion was closely correlated with nitrogen intake and urinary urea nitrogen excretion. However, on a protein-free diet the ratio of total nitrogen to sulphur in the urine was greater than when 12 g protein nitrogen was consumed. 5) There is some evidence that when total calorie intake was reduced at a level of 12 g protein nitrogen intake, the ratio of urinary urea nitrogen to urinary sulfur decreased. This suggests selective retention of some nonsulphur containing amino acids and/or selective oxidation of sulphur-containing amino acids. 6) In general, urinary calcium and magnesium excretions were depressed both with a decrease in protein consumption and a decrease in caloric intake. 7) The urinary excretions of calcium and magnesium showed a tendency to fall during the 63 days of the experiment. 8) The urinary and fecal phosphorus excretion remained constant during the various metabolic periods of the experiment.
Article
Nineteen malnourished chronic peritoneal dialysis patients who were ingesting a low protein intake underwent metabolic balance studies to test whether a dialysate that contained amino acids would improve their protein nutrition. Patients lived in the hospital for 35 days while they ate a constant diet and underwent their usual regimen of continuous ambulatory peritoneal dialysis (CAPD). The first 15 days served as a Baseline Phase. For the last 20 days, the usual dialysate was substituted with a dialysate of essentially the same composition except that it contained 1.1% essential and nonessential amino acids and no glucose. Patients received one or two dialysate exchanges with amino acids each day depending on the amount necessary to bring the individual's dietary protein plus dialysate amino acid intake to 1.1 to 1.3 g/kg body weight/day. During Baseline, patients were in neutral nitrogen balance; net protein anabolism was positive, as determined from 15N-glycine studies. After commencing intraperitoneal amino acid therapy, nitrogen balance became significantly positive, there was a significant increase in net protein anabolism, the fasting morning plasma amino acid pattern became more normal, and serum total protein and transferrin concentrations rose. Patients generally tolerated the treatment well, although some patients developed mild metabolic acidemia. These findings indicate that a dialysate containing amino acids may improve protein malnutrition in CAPD patients ingesting low protein intakes.
Article
To test the hypothesis that acidosis contributes to the insulin resistance of chronic renal failure (CRF) and impairs the action of insulin to decrease protein degradation, eight CRF patients were studied using the combined L-[1-13C]leucine-euglycemic clamp technique before (acid) and after (NaHCO3) 4 wk treatment with NaHCO3 (pH: acid 7.29 +/- 0.01 vs. NaHCO3 7.36 +/- 0.01, P < 0.001). Protein degradation (PD) was estimated sequentially from the kinetics of a primed continuous infusion of L-[1-13C]leucine in the basal state and during a hyperinsulinemic euglycemic clamp. Insulin sensitivity was measured during the clamp. The correction of acidosis significantly increased the glucose infusion rate necessary to maintain euglycemia (acid 6.44 +/- 0.89 vs. bicarbonate 7.38 +/- 0.90 mg.kg-1.min-1, P < 0.01) and significantly decreased PD in the basal state (acid 126.4 +/- 8.1 vs. bicarbonate 100.1 +/- 6.9 mumol.kg-1.h-1, P < 0.001). Hyperinsulinemia decreased PD in both studies (acid basal 126.4 +/- 8.1 vs. clamp 96.5 +/- 7.7, P < 0.001; bicarbonate basal 100.1 +/- 6.9 vs. clamp 88.2 +/- 5.5 mumol.kg-1.h-1, P = 0.06), its effect being unaltered by acidosis, with a reduction of 24% before and 12% after the correction of acidosis. In conclusion, acidosis contributes to the insulin resistance of CRF but does not affect the action of insulin on PD.
Article
The standard metabolic rate of an animal is the rate of heat production under conditions that minimize known extra requirements for energy. In tissues and cells from aerobic organisms, energy expenditure can conveniently be measured as oxygen consumption. Measurements made using isolated rat hepatocytes have shown that a significant contribution to resting oxygen consumption (and hence heat production) is made by a futile cycle of proton pumping and proton leak across the mitochondrial inner membrane. Two important factors affecting standard metabolic rate, thyroid status and phylogeny, also affect the proton permeability. A third major factor affecting standard metabolic rate is body mass. Here we show that proton leak decreases with increasing body mass in mammals. We suggest that differences in proton leak may partly explain the differences in standard metabolic rate between mammals of different mass.
Article
In a prospective randomized study, the urine pH of 170 premature and small-for-gestational-age (SGA) newborns was routinely screened to detect patients with spontaneously developing maximum renal acid stimulation, an obligatory early stage in the development of late metabolic acidosis. Nitrogen assimilation was evaluated from the ratio of urinary nitrogen excretion and intake. Forty-two premature infants and 10 SGA prematures and newborns after intensive care therapy with body weights greater than 1.5 kg and 25 prematures (including 7 SGA infants) with body weights less than 1.5 kg, spontaneously showed urine pH values below 5.4 on two consecutive days, suggesting maximum renal acid stimulation. These patients were randomly given either oral alkali therapy with sodium bicarbonate 2 mmol/kg/day or no therapy for a period of seven days. In both groups, urine pH was controlled daily. Patients in the control group without alkali therapy and with urine pH values less than 5.4 for seven days showed a significant decrease in weight gain and a tendency to decreased nitrogen assimilation. We assume that a regular check of urine pH in low-birth-weight infants is a useful non-invasive method of detecting patients in the early stages of development of late metabolic acidosis, i.e. in the stage of "incipient late metabolic acidosis". This would provide the possibility of starting early effective therapy and thereby reduce the mean duration of admission to neonatal wards.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The effect of correction of acidosis in chronic renal failure (CRF) was determined from the kinetics of infused L-[1-13C]leucine. Nine CRF patients were studied before (acid) and after two 4-wk treatment periods of sodium bicarbonate (NaHCO3) and sodium chloride (NaCl) (pH: acid 7.31 +/- 0.01, NaHCO3 7.38 +/- 0.01, NaCl 7.30 +/- 0.01). Leucine appearance from body protein (PD), leucine disappearance into body protein (PS) and leucine oxidation (O) decreased significantly with correction of acidosis (PD: acid 122.4 +/- 6.1, NaHCO3 88.3 +/- 6.9, NaCl 116.2 +/- 9.1 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.01, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS; PS: acid 109.4 +/- 5.6, NaHCO3 79.0 +/- 6.3, NaCl 101.3 +/- 7.7 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.01, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS; O: acid 13.0 +/- 1.2, NaHCO3 9.2 +/- 0.9, NaCl 15.0 +/- 1.9 mumol.kg-1.h-1, acid vs. NaHCO3 P < 0.05, NaHCO3 vs. NaCl P < 0.01, acid vs. NaCl NS). There were no significant changes in plasma amino acid concentrations. These results confirm that correction of acidosis in chronic renal failure removes a potential catabolic factor.
Article
Correction of acidosis in CAPD decreases protein degradation and synthesis but has no effect on leucine oxidation. The effect of the correction of metabolic acidosis in CRF patients treated with CAPD was determined from the kinetics of infused L-[1-13C]leucine. Seven CAPD patients were studied before (acid) and after correction of acidosis (bicarbonate) (pH:acid 7.39 +/- 0.01, bicarbonate 7.41 +/- 0.01, P = 0.005). Leucine appearance from body protein (PD) [corrected] and leucine disappearance into body protein (PS) [corrected] decreased significantly with correction of acidosis. (PS: acid 211.7 +/- 9.8, bicarbonate 142.3 +/- 4.2 micromol x kg-1 x hr-1, P < 0.001; PD: acid 200.6 +/- 8.5, bicarbonate 132.4 +/- 3.7 micromol x kg-1 x hr-1, P < 0.001). There was no significant change in leucine oxidation or plasma amino acid concentrations. These results demonstrate that optimal correction of acidosis in CAPD is beneficial in terms of protein turnover.
Article
Collegiate wrestlers (N = 12) consumed a formula, hypoenergy diet (18 kcal.kg-1, 60% carbohydrate) without dehydration for 72 h. For the next 5 h, the athletes were fed either a 75% (HC) or a 47% (MC) carbohydrate formula diet of 21 kcal.kg-1. Each wrestler performed three anaerobic arm ergometer performance tests (TEST1, before weight loss; TEST2, after weight loss; TEST3, after refeeding). Blood withdrawn just before and after each test was analyzed for pH, bicarbonate, base excess, glucose, and lactate. Both groups had a similar significant reduction in total work done during TEST2 (92.4% of TEST1). Work done in TEST3 by HC was 99.1% of TEST1 while MC did 91.5% of their initial work (P = 0.1). Peak power was unaffected by the treatment. Plasma lactate significantly increased during the performance test from 1.72 to 21.91 mmol.l-1 as did plasma glucose from 4.88 to 5.25 mmol.l-1 when groups and trials were collapsed. Lactate accumulation was diminished during TEST2 compared with the other tests. Although the exercise bout reduced pH, bicarbonate, and base excess, there was no difference in the effect by group. In conclusion, weight loss by energy restriction significantly reduced anaerobic performance of wrestlers. Those on a high carbohydrate refeeding diet tended to recover their performance while those on a moderate carbohydrate diet did not. The changes in performance were not explained by the acid/base parameters measured.
Article
The effects of metabolic acidosis on thyroid function are unknown. We investigated the effects of chronic extrarenal acidosis on the hypothalamic-pituitary-thyroid axis. Chronic metabolic acidosis was induced by administering NH4Cl (4.2 mmol.kg body wt-1.day-1) to six normal male volunteers during metabolic balance conditions. Plasma bicarbonate concentration decreased from 25.0 +/- 0.4 to 15.5 +/- 0.9 mmol/l (P < 0.001). Metabolic acidosis significantly decreased serum-free 3,5,3'-triiodothyronine (T3) concentrations from 373 +/- 18 (control) to 251 +/- 13 pg/dl (P < 0.001) and decreased serum-free L-thyroxine (T4) from 1.55 +/- 0.42 to 1.25 +/- 0.37 ng/dl (P < 0.002), whereas serum total reverse T3 did not change significantly. Consequently, the reverse T3-to-free T4 ratio increased. Serum thyroid-stimulating hormone (TSH) levels increased significantly from 0.70 +/- 0.07 during control to 1.30 +/- 0.12 mU/l during acidosis (P < 0.003). The TSH response to thyrotropin (TRH, 2 mg intranasally) was exaggerated in acidosis: the partial area under the concentration curve for the TSH response (210 min post-TRH) was 902 +/- 167 during control compared with 1.394 +/- 209 mU.min.l-1 during acidosis (P = 0.0139). Chronic metabolic acidosis, as produced by the model employed here, induces a decrease in thyroid hormone secretion and might exert additional effects on thyroid hormone metabolism in humans. The acidosis-induced decrease in thyroid function might modulate some of the reported effects of metabolic acidosis, such as on nitrogen balance, protein synthesis, lean body mass, insulin-like growth factor I levels, renal acidification, and cardiac contractile function.
Article
The aim of this study was to assess the impact of an amino acid-based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome. Four children (23 months-4.75 years) with short bowel syndrome who required long-term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid-based complete infant formula for a mean follow-up period of 48 months (range 39-51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin-prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability. All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven (mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/ patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly (mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies. An amino acid-based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long-term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.
Article
Under normal physiologic conditions, acid–base balance is maintained by renal excretion of hydrogen ions generated during the metabolism of dietary protein and other metabolic processes. In normal subjects, these so-called fixed acids are produced at an average rate of approximately 1 mmol per kilogram of body weight, or 50 to 70 mmol per day, with a variety of organic acids accounting for half this amount and sulfuric and phosphoric acids for the remainder. When a disturbance in systemic pH occurs as the result of an excess or loss of acid or base, shifts in body buffers and ventilatory adjustment of . . .
Article
Glutathione deficiency has been associated with a number of neurodegenerative diseases including Lou Gehrig's disease, Parkinson's disease, and HIV. A crucial role for glutathione is as a free radical scavenger. Alzheimer's disease (AD) brain is characterized by oxidative stress, manifested by protein oxidation, lipid oxidation, oxidized glutathione, and decreased activity of glutathione S-transferase, among others. Reasoning that elevated levels of endogenous glutathione would offer protection against free radical-induced oxidative stress, rodents were given in vivo injections of N-acetylcysteine (NAC), a known precursor of glutathione, to study the vulnerability of isolated synaptosomal membranes treated with Fe2+/H2O2, a known hydroxyl free radical producer. Protein carbonyls, a marker of protein oxidation, were measured. NAC significantly increased endogenous glutathione levels in cortical synaptosome cytosol (P < 0.01). As reported previously, protein carbonyl levels of the Fe2+/H2O2-treated synaptosomes were significantly higher compared to that of non-treated controls (P < 0.01), consistent with increased oxidative stress. In contrast, protein carbonyl levels in Fe2+/H2O2-treated synaptosomes isolated from NAC-injected animals were not significantly different from saline-injected non-treated controls, demonstrating protection against hydroxyl radical induced oxidative stress. These results are consistent with the notion that methods to increase endogenous glutathione levels in neurodegenerative diseases associated with oxidative stress, including AD, may be promising.
Article
There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species and mitochondrial dysfunction. Here, we review the evidence for a disturbance of glutathione homeostasis that may either lead to or result from oxidative stress in neurodegenerative disorders. Glutathione is an important intracellular antioxidant that protects against a variety of different antioxidant species. An important role for glutathione was proposed for the pathogenesis of Parkinson's disease, because a decrease in total glutathione concentrations in the substantia nigra has been observed in preclinical stages, at a time at which other biochemical changes are not yet detectable. Because glutathione does not cross the blood-brain barrier other treatment options to increase brain concentrations of glutathione including glutathione analogs, mimetics or precursors are discussed.
Article
Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.
Article
A variety of degenerative diseases have now been shown to be caused by mutations in mitochondrial genes encoded by the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). The mitochondria generate most of the cellular energy by oxidative phosphorylation (OXPHOS), and produce most of the toxic reactive oxygen species (ROS) as a by-product. Genetic defects that inhibit OXPHOS also cause the redirection of OXPHOS electrons into ROS production, thus increasing oxidative stress. A decline in mitochondrial energy production and an increase in oxidative stress can impinge on the mitochondrial permeability transition pore (mtPTP) to initiate programmed cell death (apoptosis). The interaction of these three factors appear to play a major role on the pathophysiology of degenerative diseases. Inherited diseases can result from mtDNA base substitution and rearrangement mutations and can affect the CNS, heart and skeletal muscle, and renal, endocrine and haematological systems. In addition, somatic mtDNA mutations accumulate with age in post-mitotic tissues in association with the age-related decline in mitochondrial function and are thought to be an important factor in ageing and senescence. The importance of mitochondrial defects in degenerative diseases and ageing has been demonstrated using mouse models of mitochondrial disease. An mtDNA mutation imparting chloramphenical resistance (CAPR) to mitochondrial protein synthesis has been transferred into mice and resulted in growth retardation and cardiomyopathy. A nDNA mutation which inactivates the heart-muscle isoform of the adenine nucleotide translocator (Ant1) results in mitochondrial myopathy and cardiomyopathy; induction of ROS production; the compensatory up-regulation of energy, antioxidant, and apoptosis gene expression; and an increase in the mtDNA somatic mutation rate. Finally, a nDNA mutation which inactivates the mitochondrial Mn superoxide dismutase (MnSOD) results in death in about 8 days due to dilated cardiomyopathy, which can be ameliorated by treatment with catalytic anti-oxidants. A partial MnSOD deficiency chronically increases oxidative stress, decreases OXPHOS function, and stimulates apoptosis. Thus, the decline of mitochondrial energy production resulting in increased oxidative stress and apoptosis does play a significant role in degenerative diseases and ageing.
Article
Obesity is currently considered as a chronic metabolic disease, associated with a high risk of cardiovascular complications. Leptin, an adipocyte-derived hormone has a variety target cells influencing a wide range of processes. Possible counteractions of hyperleptinaemia are currently investigated. The Na(+)-H(+) exchanger (NHE 1) is involved in multiple cellular functions and its activation has been related to hypertension and obesity. NHE 1 is present on erythrocytes and can be stimulated by various hormones. Erythrocytes have on their surface a variety of receptors with mostly unknown function. In the present paper, the effect of leptin on erythrocytes NHE 1 activity has been investigated. For this reason, the intracellular pH and sodium influxes were measured before and after addition of leptin in erythrocyte suspensions from normal and obese individuals. Amiloride, a specific NHE 1 inhibitor, and staurosporine a protein kinase C inhibitor were used to inhibit erythrocyte NHE 1. For the binding study leptin was labeled with fluorescein isothiocyanate (FITC) and the binding on erythrocytes was estimated by Scatchard analysis. NHE 1 activity increased in the presence of leptin but significantly less in the obese than in the control group. Furthermore the concentrations of leptin binding sites on the surface of erythrocytes were lower in erythrocytes drawn from obese individuals than in erythrocytes drawn from normal subjects. Since NHE 1 activity has been associated with insulin resistance and hypertension, the activation of this antiport by leptin may represent a link between adipose tissue hypertrophy and cardiovascular complications of obesity.