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Nutritional Prevention and Acid Base Status

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (30 March 2018) | Viewed by 80973

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Prof. Dr. Thomas Remer

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DONALD Study Center Dortmund, Nutritional Epidemiology, Institute of Nutritional and Food Sciences, University of Bonn, Heinstück 11, 44225 Dortmund, Germany
Interests: acid-base metabolism and its interrelationships with nutrition, hormones, and health-relevant outcomes; steroid metabolome (cortisol metabolism, prepubertal sex hormones), adrenarche and their interrelations with nutrition and growth; identification and characterization of non-invasive biomarkers of nutrition and growth; iodine nutrition
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Prof. Dr. Lynda A. Frassetto

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Division of Nephrology, School of Medicine, University of California, 505 Parnassus Ave, Campus Box 0126, San Francisco, CA 94143, USA
Interests: paleo diet and health; acid-base balance; uremic toxins; artificial kidney; HIV-transplant drug interactions; cell membrane transporter-metabolizing enzyme interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Nutritional Prevention and Acid Base Status”, of Nutrients invites manuscripts, both reviews and original research articles, in the field of preventive nutrition and nutritional behavior with a special research focus on the health-relevant impacts exerted by base forming minerals, physician-initiated alkalization, and reductions in dietary acid loads.

Dietary influences on acid-base balance have been, until recently, an esoteric branch of research. Over the last one to two decades however, scientists from different disciplines have shown increasing interest in understanding both the daily and the long term impact of one’s dietary intake of acid and base equivalents on health. These influences are present from childhood, and over a lifetime can potentially contribute to a variety of chronic disorders including hypertension, insulin resistance, progression of chronic kidney and cardiovascular diseases, kidney stones, gout, osteoporosis, and age-related decline in muscle mass.

Both observational and interventional studies have demonstrated positive health-related associations and beneficial metabolic effects on major biological outcomes through increases in dietary or supplemental alkali loads. Yet, not all corresponding studies have reported conclusive results. Numerous reasons may account for these discrepancies. Among them are the lack of appropriate accounting of:

- measurement validity, e.g., the inadequate measurement of free protons (urine-pH) or net acid excretion parameters in spot urine instead of 24-h urine samples
- relevant anabolic effects of dietary protein intake
- acid-base effects of many dietary supplements, e.g., the clear alkalizing potential of most calcium supplements used worldwide
- important endocrine players (confounders) affecting the inner hormonal and metabolic milieu, e.g. corticosteroids or the insulin-like growth factor system
- methodologic weaknesses of many exposition measurements, e.g., only an onetime use of a less accurate diet questionnaire
- methodologic weaknesses of outcome measurements e.g., the determination of “BMI-only” instead of fat mass indices or of areal bone mineral density instead of volumetric density, bone strength, and bone geometry
- (patho)physiologically different subpopulations, e.g., the non-exclusion of subjects on medications with contrasting outcome effects
- kidney function in studies with a broad variability in renal function parameters

Against this background, this Special Issue will include original research and scientific perspectives on how, and to what extent dietary intake of acid and base equivalents does affect the body’s acid base balance, with a clear focus on (patho)physiologic consequences of these interactions.

Manuscripts covering all ages from young childhood to old adulthood are welcome that may include, but are not limited to, the following topics related to the influences of diet-, mineral-, or metabolism-dependent changes in endogenous net proton loads:

▪ Blood pressure, Hypertension
▪ Insulin Resistance, Glucose Control, Diabetes
▪ Chronic Kidney Disease
▪ Kidney Stones
▪ Cardiovascular Disease
▪ Hyperuricemia, Gout
▪ Bone Architecture, Bone Quality, Osteoporosis, Fracture Risk
▪ Muscle Mass, Sarcopenia
▪ Fat Mass, Obesity
▪ Corticosteroids, Aldosterone, Cortisol, Cortisone
▪ Insulin-like Growth Factor System, Growth

Prof. Dr. Thomas Remer
Prof. Dr. Lynda A. Frassetto
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Acid-base balance
Acidosis
Alkalizing minerals
Bicarbonate
Bone architecture
Cardiovascular disease
Citrate
Corticosteroids
DASH diet
Fruits and vegetables
Glucose control
Hypertension
Hyperuricemia
Insulin resistance
Kidney stones
Muscle mass and function
Net acid excretion (NAE)
Obesity
Osteoporosis
Paleo diet
Potential renal acid load (PRAL)
Progression of chronic kidney disease (CKD)

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Published Papers (10 papers)

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Research

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15 pages, 786 KiB

Open AccessArticle

Dietary Influence on Body Fluid Acid-Base and Volume Balance: The Deleterious “Norm” Furthers and Cloaks Subclinical Pathophysiology

by Qi Qian

Nutrients 2018, 10(6), 778; https://doi.org/10.3390/nu10060778 - 16 Jun 2018

Cited by 5 | Viewed by 11920

Abstract

The popular modern diet, characterized by an excess of animal protein and salt but insufficient in fruits, vegetables and water, is a poor fit for human physiological and homeostatic regulatory systems. Sustained net acid and sodium retention, coupled with an insufficient intake of cardiovascular protective potassium-rich foods and hydration in the modern diet can give rise to debilitating chronic organ dysfunction and ultimately, mortality. This holds true, especially in our aging population who are already facing inevitable decline in organ functional reserve. Importantly, in most cases, despite the mismatch and adverse effects to multiple organ systems, plasma electrolyte and acid-base parameters can, on the surface, be maintained within a “normal” reference range, primarily by activating (often maximally activating) compensatory homeostatic mechanisms. These diet-induced effects can thus be clinically silent for decades. Embodied in the chronic corrective homeostatic processes, however, are real risks for multiorgan damage. According to the Dietary Guideline Advisory Committee (DGAC), half of American adults have one or more chronic diseases that are preventable with dietary modification. Here, homeostasis of body fluid acid-base, sodium, potassium and water is examined. Our current dietary habits and their required regulatory adaptation, maladaptation and relevant physiology and pathophysiology are discussed. A framework of dietary modifications to avoid a propensity for maladaptation and thus lowers the risks of common modern diseases (primary prevention) and minimizes the risk of chronic and age-related disease progression (secondary prevention) is emphasized. Although there are other variables at play, a key to restoring the all-important dietary potassium to sodium ratio is greater consumption of vegetables/fruits and adopting salt temperance. Dietary and nutritional optimization is an under-emphasized area of health care that has an enormous potential to temper the epidemics of prevalent chronic diseases in modern society and improve population health. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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11 pages, 1007 KiB

Open AccessArticle

Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men

by Lee M. Margolis, Lisa Ceglia, Donato A. Rivas, Bess Dawson-Hughes and Roger A. Fielding

Nutrients 2018, 10(5), 624; https://doi.org/10.3390/nu10050624 - 16 May 2018

Cited by 2 | Viewed by 4535

Abstract

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day⁻¹ potassium bicarbonate (KHCO₃) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO₃; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day⁻¹) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO₃ or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (¹⁵N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was −9.8 ± 27.8 mmol∙day⁻¹ in KHCO₃ and 43.9 ± 27.8 mmol∙day⁻¹ in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO₃ vs. PLA following energy restriction, and NAE was inversely associated (r = −0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO₃ supplementation following energy restriction as lower NAE indicated higher urea synthesis. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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13 pages, 1116 KiB

Open AccessArticle

Kidney Response to the Spectrum of Diet-Induced Acid Stress

by Nimrit Goraya and Donald E. Wesson

Nutrients 2018, 10(5), 596; https://doi.org/10.3390/nu10050596 - 11 May 2018

Cited by 7 | Viewed by 4173

Abstract

Chronic ingestion of the acid (H⁺)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H⁺ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H⁺ excretion is less than the cumulative increment in dietary H⁺, consistent with H⁺ retention. This H⁺ retention associated with the described high dietary H⁺ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H⁺ retention does not measurably change plasma acid–base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H⁺ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H⁺ injury, which we characterize as “H⁺ stress”, and the emerging evidence that high dietary H⁺ constitutes a threat to long-term kidney health. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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12 pages, 272 KiB

Open AccessArticle

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply—A Pilot Study

by Janice W. Y. Wong, Hugo A. E. Morandini, Vita L. S. Dingerkus, Tilman J. Gaber, Kevin C. Runions, Pradeep Rao, Simone Mahfouda, Katrin Helmbold, Sarah Bubenzer-Busch, Rebecca Koenemann, Richard M. Stewart and Florian D. Zepf

Nutrients 2018, 10(5), 594; https://doi.org/10.3390/nu10050594 - 11 May 2018

Viewed by 3914

Abstract

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

16 pages, 560 KiB

Open AccessFeature PaperArticle

Dietary Acid Load and Mental Health Outcomes in Children and Adolescents: Results from the GINIplus and LISA Birth Cohort Studies

by Judith Bühlmeier, Carla Harris, Sibylle Koletzko, Irina Lehmann, Carl-Peter Bauer, Tamara Schikowski, Andrea Von Berg, Dietrich Berdel, Joachim Heinrich, Johannes Hebebrand, Manuel Föcker, Marie Standl and Lars Libuda

Nutrients 2018, 10(5), 582; https://doi.org/10.3390/nu10050582 - 8 May 2018

Cited by 20 | Viewed by 6146

Abstract

High dietary acid load may have detrimental effects on mental health during childhood and adolescence. We examined cross-sectional and prospective associations of dietary acid load and mental health problems in a population-based sample, using data from the German birth cohort studies GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISA (Influences of lifestyle-related factors on the immune system and the development of allergies in childhood). These studies included detailed assessments of dietary intake through a food frequency questionnaire (FFQ), mental health outcomes measured through the Strengths and Difficulties Questionnaire (SDQ), and covariates. Using logistic regression, cross-sectional associations between dietary acid load measured as potential renal acid load (PRAL) and SDQ subscales were assessed at age 10 years (N = 2350) and 15 years (N = 2061). Prospective associations were assessed, considering PRAL at 10 years as exposure and SDQ subscales at 15 years as outcome (N = 1685). Results indicate that children with a diet higher in PRAL have more emotional problems (OR = 1.33 (95% CI = 1.15; 1.54); p < 0.001), and show hyperactivity more often (1.22 (1.04; 1.43); p = 0.014) at 10 years. No significant associations were present either cross-sectionally at age 15 years, nor prospectively. Results were confirmed in sensitivity analyses. These findings reveal first evidence for potential relationships between PRAL and mental health in childhood, although we cannot exclude reverse causality, i.e., that dietary behavior and PRAL are influenced by mental status. Future studies should address confirmation and identify biological mechanisms. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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12 pages, 1620 KiB

Open AccessArticle

Effects of 12-Week Low or Moderate Dietary Acid Intake on Acid–Base Status and Kidney Function at Rest and during Submaximal Cycling

by Enni-Maria Hietavala, Johanna K. Ihalainen, Lynda A. Frassetto, Moritz Schumann, Daniela Eklund, Hannu Pitkänen, Keijo Häkkinen and Antti A. Mero

Nutrients 2018, 10(3), 323; https://doi.org/10.3390/nu10030323 - 8 Mar 2018

Cited by 5 | Viewed by 6308

Abstract

Prolonged effects of dietary acid intake on acid–base status and kidney function have not yet been studied in an intervention study in healthy subjects. Dietary acid load can be estimated by calculating the potential renal acid load (PRAL) of foods. Effects of low-PRAL and moderate-PRAL diets on acid–base status and kidney function were investigated during a 12-week exercise training period. Healthy, 20–50-year-old men (n = 21) and women (n = 25) participated in the study and were randomly divided into low-PRAL and moderate-PRAL groups. Before (PRE), mid-phase (MID) and after the intervention (POST), the subjects participated in measurement sessions, where a 12-h urine sample and fasting blood samples were collected, and a submaximal cycle ergometer test was performed. Net acid excretion was significantly lower after 12 weeks of the low-PRAL diet as compared to the moderate-PRAL diet, both in men and women. In low-PRAL females, capillary pH and bicarbonate were significantly higher at 75% of VO_2max at POST as compared to PRE. Glomerular filtration rate decreased over the study period in moderate-PRAL men and women. The results of the present study suggest that an acidogenic diet and regularly training together may increase the acidic load of the body and start to impair the kidney function in recreationally active subjects. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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14 pages, 611 KiB

Open AccessFeature PaperArticle

Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population

by Danika Krupp, Jonas Esche, Gert Bernardus Maria Mensink, Stefanie Klenow, Michael Thamm and Thomas Remer

Nutrients 2018, 10(1), 103; https://doi.org/10.3390/nu10010103 - 19 Jan 2018

Cited by 32 | Viewed by 7810

Abstract

Diets rich in fruits and vegetables, like the Dietary Approaches to Stop Hypertension (DASH)-diet, are usually characterized by high potassium intake and reduced dietary acid load, and have been shown to reduce blood pressure (BP). However, the relevance of potential renal acid load (PRAL) for BP has not been compared with the relevance to BP of urinary biomarker (K-urine)- and dietary food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a general adult population sample. For 6788 participants (aged 18–79 years) of the representative German Health-Interview and Examination Survey for Adults (DEGS1), associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were cross-sectionally examined in multivariable linear and logistic regression models. PRAL was significantly associated with higher systolic BP (p = 0.0002) and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p = 0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium intake, kidney function, relevant medication, and further important covariates. Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04 and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR = 0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our results show, for the first time in a comparative analysis of a large representative population sample, significant relationships of BP and hypertension prevalence with questionnaire- and biomarker-based estimates of potassium intake and with an estimate of dietary acid load. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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Review

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17 pages, 529 KiB

Open AccessReview

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

by Lucio Della Guardia, Michael Alex Thomas and Hellas Cena

Nutrients 2018, 10(5), 618; https://doi.org/10.3390/nu10050618 - 15 May 2018

Cited by 27 | Viewed by 7479

Abstract

Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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9 pages, 252 KiB

Open AccessReview

Acid Balance, Dietary Acid Load, and Bone Effects—A Controversial Subject

by Lynda Frassetto, Tanushree Banerjee, Neil Powe and Anthony Sebastian

Nutrients 2018, 10(4), 517; https://doi.org/10.3390/nu10040517 - 21 Apr 2018

Cited by 67 | Viewed by 15151

Abstract

Modern Western diets, with higher contents of animal compared to fruits and vegetable products, have a greater content of acid precursors vs. base precursors, which results in a net acid load to the body. To prevent inexorable accumulation of acid in the body and progressively increasing degrees of metabolic acidosis, the body has multiple systems to buffer and titrate acid, including bone which contains large quantities of alkaline salts of calcium. Both in vitro and in vivo studies in animals and humans suggest that bone base helps neutralize part of the dietary net acid load. This raises the question of whether decades of eating a high acid diet might contribute to the loss of bone mass in osteoporosis. If this idea is true, then additional alkali ingestion in the form of net base-producing foods or alkalinizing salts could potentially prevent this acid-related loss of bone. Presently, data exists that support both the proponents as well as the opponents of this hypothesis. Recent literature reviews have tended to support either one side or the other. Assuming that the data cited by both sides is correct, we suggest a way to reconcile the discordant findings. This overview will first discuss dietary acids and bases and the idea of changes in acid balance with increasing age, then review the evidence for and against the usefulness of alkali therapy as a treatment for osteoporosis, and finally suggest a way of reconciling these two opposing points of view. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

8 pages, 855 KiB

Open AccessReview

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease

by Roswitha Siener

Nutrients 2018, 10(4), 512; https://doi.org/10.3390/nu10040512 - 20 Apr 2018

Cited by 34 | Viewed by 12024

Abstract

Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid–base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8–1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources. Full article

(This article belongs to the Special Issue Nutritional Prevention and Acid Base Status)

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