Reducing dietary crude protein (CP) concentration while maintaining adequate amino acid (AA) supply by free AA inclusion can contribute to attenuate the negative environmental effects of animal farming. This study investigated upper limits of dietary free AA inclusions without undesirable effects including the dependence on asparagine (Asn) and glutamine (Gln) supply. Ten broilers were allocated to sixty-three metabolism units each and offered nine experimental diets from day (d) 7–21 (n 7). One diet (167 g CP/kg) contained 80 g soya protein isolate (SPI)/kg. In the other diets, 25, 50, 75 and 100 % of the digestible AA from SPI were substituted with free AA. Digestible Asn+aspartic acid (Asp) and Gln+glutamic acid (Glu) were substituted with Asp/Glu or 50/50 mixes of Asp/Asn and Glu/Gln, respectively. Total excreta were collected from d 11–14 and from d 18–21. Growth and nitrogen accretion were unaffected by 25 and 50 % substitution without and with free Asn/Gln, respectively, but decreased at higher substitution (P ≤ 0·024). Circulating concentrations of Asp, Glu and Gln were unaffected by treatment, while Asn decreased at substitution higher than 50 % when Asn/Gln were not provided (P ≤ 0·005). Blood gas analysis on d 21 indicated a compensated metabolic acidosis at substitution higher than 50 and 75 % without and with free Asn/Gln, respectively (P ≤ 0·017). Results suggest that adding Asn/Gln increased an upper limit for proportion of dietary free AA from 10 to 19 % of dietary CP and enabled higher free AA inclusion without affecting the acid–base balance.

This study was designed to evaluate the effects of elevated fruit and vegetable intake on bone turnover markers. In all, twenty-nine subjects (nine male and twenty female, with a mean age of 32·1 (sem 2·5) years) participated in a 28-week single-arm experimental feeding intervention trial and consumed a prescribed low-fruit and vegetable diet for 6 weeks (depletion-1), a provided high-fruit and vegetable diet for 8 weeks (fruit: 360–560 g; vegetables: 450–705 g), another prescribed low-fruit and vegetable diet for 6 weeks (depletion-2) and then their usual diets for 8 weeks (repletion). Serum bone-related biomarkers were analysed with commercial ELISA kits. Plasma carotenoid levels decreased as a result of the depletion phase and increased with the high-fruit and vegetable diet. Compared with the baseline, depletion-1 resulted in higher serum bone resorption marker C-terminal telopeptide of type 1 collagen (CTX) and lower bone formation marker alkaline phosphatase (BAP) (CTX, 0·68 (sem 0·05) v. 0·97 (sem 0·08) ng/ml and BAP, 10·7 (sem 0·7) v. 9·5 (sem 0·8) µg/l for the baseline and the depletion-1, respectively, P<0·05). High intake of fruit and vegetables decreased serum CTX (P<0·05) to 0·60 (sem 0·04) ng/ml and increased serum BAP to 11·3 (sem 0·7) µg/l (P<0·05), compared with the depletion-1 phase. Serum concentrations of CTX were inversely correlated and those of BAP were positively correlated with blood lycopene. These data show that increased fruit and vegetable consumption at or above federal dietary guidance may be beneficial to bone health.

The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid–base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid–base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid–base and Ca homeostasis.

Predisposition to poor skeletal health resulting in osteoporotic fracture is a major public health problem, the future economical impact of which is likely to be phenomenal. Two mechanisms principally determine adult bone health: (1) maximum attainment of peak bone mass (PBM); (2) the rate of bone loss with advancing age. Both aspects are regulated by a combination of endogenous and exogenous factors, and although genetic influences are believed to account for up to 75 % of the variation in bone mass, there is still room for modifiable factors to play a vital role. Weight-bearing physical activity is beneficial to the skeleton, but clarification of the exact type, intensity and duration required for optimum bone mass is needed. Excessive levels of exercise, which result in amenorrhoea, are detrimental to skeletal health. The importance of Ca to bone remains controversial. There is evidence that Ca is effective in reducing late post-menopausal bone loss, but more research is required on the long-term benefit of increased Ca intake on PBM attainment. Vitamin D ‘insufficiency’ appears to be widespread amongst population groups and is an area of considerable public health concern. The role of other micronutrients on bone metabolism remains to be fully quantified, but data from a combination of experimental, clinical and observational studies suggest a positive link between alkaline-forming foods and indices of bone health. The influence of nutrient–gene interactions on the skeleton requires further elucidation, but it may be useful in the future to target nutrition advice at those individuals who are genetically susceptible to osteoporosis.

The effect of short-term (5 days) exposure to CO2-acidified seawater (year 2100 predicted values, ocean pH = 7.6) on key aspects of the function of the intertidal common limpet Patella vulgata (Gastropoda: Patellidae) was investigated. Changes in extracellular acid–base balance were almost completely compensated by an increase in bicarbonate ions. A concomitant increase in haemolymph Ca2+ and visible shell dissolution implicated passive shell dissolution as the bicarbonate source. Analysis of the radula using SEM revealed that individuals from the hypercapnic treatment showed an increase in the number of damaged teeth and the extent to which such teeth were damaged compared with controls. As radula teeth are composed mainly of chitin, acid dissolution seems unlikely, and so the proximate cause of damage is unknown. There was no hypercapnia-related change in metabolism (O2 uptake) or feeding rate, also discounting the possibility that teeth damage was a result of a CO2-related increase in grazing. We conclude that although the limpet appears to have the physiological capacity to maintain its extracellular acid–base balance, metabolism and feeding rate over a 5 days exposure to acidified seawater, radular damage somehow incurred during this time could still compromise feeding in the longer term, in turn decreasing the top-down ecosystem control that P. vulgata exerts over rocky shore environments.

There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods. Western diets consumed by adults generate approximately 50–100 mEq acid/d; therefore, healthy adults consuming such a diet are at risk of chronic low-grade metabolic acidosis, which worsens with age as a result of declining kidney function. Bone buffers the excess acid by delivering cations and it is considered that with time an overstimulation of this process will lead to the dissolution of the bone mineral content and hence to reduced bone mass. Intakes of K, Mg and fruit and vegetables have been associated with a higher alkaline status and a subsequent beneficial effect on bone health. In healthy male volunteers an acid-forming diet increases urinary Ca excretion by 74% and urinary C-terminal telopeptide of type I collagen (C-telopeptide) excretion by 19% when compared with an alkali (base-forming) diet. Cross-sectional studies have shown that there is a correlation between the nutritional acid load and bone health measured by bone ultrasound or dual-energy X-ray absorptiometry. Few studies have been undertaken in very elderly women (>75 years), whose osteoporosis risk is very pertinent. The EVAluation of Nutrients Intakes and Bone Ultra Sound Study has developed and validated (n 51) an FFQ for use in a very elderly Swiss population (mean age 80·4 (sd 2·99) years), which has shown intakes of key nutrients (energy, fat, carbohydrate, Ca, Mg, vitamin C, D and E) to be low in 401 subjects. A subsequent study to assess net endogenous acid production (NEAP) and bone ultrasound results in 256 women aged ≥75 years has shown that lower NEAP (P=0·023) and higher K intake (P=0·033) are correlated with higher bone ultrasound results. High acid load may be an important additional risk factor that may be particularly relevant in very elderly patients with an already-high fracture risk. The latter study adds to knowledge by confirming a positive link between dietary alkalinity and bone health indices in the very elderly. In a further study to complement these findings it has also been shown in a group of thirty young women that in Ca sufficiency an acid Ca-rich water has no effect on bone resorption, while an alkaline bicarbonate-rich water leads to a decrease in both serum parathyroid hormone and serum C-telopeptide. Further investigations need to be undertaken to study whether these positive effects on bone loss are maintained over long-term treatment. Mineral-water consumption could be an easy and inexpensive way of helping to prevent osteoporosis and could be of major interest for long-term prevention of bone loss.

Contrasting data are published on the effects of high salt intake (between 300 and 660 mmol/d) on Na balance and fluid retention. In some studies high levels of NaCl intake (400, 440, 550 and 660 mmol/d) led to positive Na balances without fluid retention. To test the relevance of different baseline NaCl intake levels on changes in metabolic water, Na, K, chloride and acid–base balance, a 28 d clinical trial (‘Salty Life 6’) was carried out in a metabolic ward. Nine healthy male volunteers (aged 25·7 (sd 3·1) years; body mass (BM) 71·4 (sd 4·0) kg) participated in the present study. Four consecutive levels of NaCl intake: low (6 d, 0·7 mmol NaCl/kg BM per d), average normal (6 d, 2·8 mmol NaCl/kg BM per d), high (10 d, 7·7 mmol NaCl/kg BM per d), and low again (6 d, 0·7 mmol NaCl/kg BM per d) were tested. Urine osmolality, extracellular volume (ECV) and plasma volume (PV), cumulative metabolic Na, K, chloride and fluid balances, mRNA expression of two glycosaminoglycan (GAG) polymerisation genes, capillary blood pH, bicarbonate and base excess were measured. During average normal NaCl intake, 193 (sem 19) mmol Na were retained and ECV (+2·02 (sem 0·31) litres; P < 0·001) and PV (+0·57 (sem 0·13) litres; P < 0·001) increased. During high NaCl intake, 244 (sem 77) mmol Na were retained but ECV did not increase (ECV − 0·54 (sem 0·30) litres, P = 0·089; PV +0·27 (sem 0·25) litres, P = 0·283). mRNA expression of GAG polymerisation genes increased with rise in NaCl intake, while pH (P < 0·01) and bicarbonate (P < 0·001) levels decreased. We conclude that a high NaCl intake may increase GAG synthesis; this might play a role in osmotically inactive Na retention in humans.

The objectives were to investigate the effects on fluid balance, digestion and exercise response in Standardbred horses in race training when feeding silage, haylage or hay-only diets. In experiment (exp) 1, five Standardbred geldings were fed forage-only diets: hay (82% dry matter, DM) and silage (45% DM) for 23 days in a crossover design. Total collection of faeces and urine was performed. In exp 2, six Standardbred geldings were fed forage-based diets: haylage (68% DM) and silage (41% DM) for 17 days in a crossover design. On day 17, an incremental interval exercise test was performed on an oval racetrack. In exp 1, horses drank more on the hay than on the silage diet, but total water intake (drinking+water in feed) was higher and resting values of total plasma protein (TPP) was lower on the silage diet. Total water output per day did not differ and therefore the estimated evaporation was larger on the silage than the hay diet. The apparent digestibility was higher on the silage than the hay diet. In exp 2, heart and respiratory rate, TPP and lactate and blood pH did not differ between the haylage and silage diets during and after the exercise test. In conclusion, feeding silage did not affect faecal water content, but apparent digestibility and estimated evaporative fluid loss were higher on the silage diet compared with the hay diet. The silage did not adversely affect the response to intensive exercise compared with haylage. However, the estimated higher evaporative fluid loss on the silage diet compared with the hay diet might cause an unnecessary challenge during more prolonged exercise.

The consumption of mineral waters is increasing in industrialised countries. High intakes of Ca and other alkalising cations as well as a low acid intake are beneficial to bone. We examined which components of mineral waters are conditioning their Ca content and their alkalinising power, in order to define the optimal profile. European mineral waters were randomly selected on the Internet: 100 waters with less than 200 mg Ca/l (9·98 mEq/l) and fifty with more than 200 mg/l, all with complete data for SO4, P, Cl, Na, K, Mg and Ca, and most also for HCO3. For comparison, forty North American mineral waters were randomly chosen. The potential renal acid load (PRAL) was calculated for each mineral water. North American waters did not reveal significant results because of their low mineralisation. We performed correlations between all eight components in order to explore the properties of the mineral waters. In the European waters, twenty-six out of twenty-eight correlations showed a P value of ≤ 0·01. In waters with PRAL >0 (acidifying waters), PRAL was positively correlated with SO4, Ca, K and Mg (P < 0·001). In those with PRAL < 0 (alkalinising waters), PRAL was negatively correlated with HCO3, Na, Mg, Ca, K, Cl and SO4 (P < 0·001). SO4 and HCO3 were not found together in high quantities in the same water for geochemical reasons. A high Ca content is associated with either a high SO4 or a high HCO3 content. SO4 theoretically increases Ca excretion, while HCO3 and low PRAL values are associated with positive effects on bone. Therefore, the best waters for bone health are rich in both HCO3 and Ca, and by consequence low in SO4.

Evidence exists that a more acidic diet is detrimental to bone health. Although more precise methods exist for measurement of acid–base balance, urine pH reflects acid–base balance and is readily measurable but has not been related to habitual dietary intake in general populations. The present study investigated the relationship between urine pH and dietary acid–base load (potential renal acid load; PRAL) and its contributory food groups (fruit and vegetables, meats, cereal and dairy foods). There were 22 034 men and women aged 39–78 years living in Norfolk (UK) with casual urine samples and dietary intakes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk FFQ. A sub-study (n 363) compared pH in casual samples and 24 h urine and intakes from a 7 d diary and the FFQ. A more alkaline diet (low PRAL), high fruit and vegetable intake and lower consumption of meat was significantly associated with a more alkaline urine pH before and after adjustment for age, BMI, physical activity and smoking habit and also after excluding for urinary protein, glucose, ketones, diagnosed high blood pressure and diuretic medication. In the sub-study the strongest relationship was found between the 24 h urine and the 7 d diary. In conclusion, a more alkaline diet, higher fruit and vegetable and lower meat intake were related to more alkaline urine with a magnitude similar to intervention studies. As urine pH relates to dietary acid–base load its use to monitor change in consumption of fruit and vegetables, in individuals, warrants further investigation.

Dietary intake has been shown to influence acid–base balance in human subjects under tightly controlled conditions. However, the net effect of food groups on alkali/acid loading in population groups is unclear. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a representative group of British elderly aged 65 years and older; (2) compare and characterise NEAP by specific nutrients and food groups likely to influence dietary acid loading; (3) determine whether geographical location influenced NEAP. The National Diet and Nutrition Survey dataset, consisting of a 4 d weighed record and anthropometric data, was used to estimate dietary acidity. Dietary under-reporters were excluded by analysing only subjects with energy intakes ≥ 1·2 × BMR. NEAP was estimated as the dietary potential renal acid load+organic acid excretion, the latter as a multiple of estimated body surface area. NEAP was lower in women compared with men (P < 0·001), and lower than values reported in a Swedish elderly cohort. Lower dietary acidity was significantly associated with higher consumption of fruit and potatoes and lower consumption of meat, bread and eggs (P < 0·02 to P < 0·001). Lower intakes of fish and cheese were associated with lower NEAP in men only (P < 0·01 to P < 0·001). There were regional differences for NEAP, with higher intakes in Scotland/Northern regions compared with Central/South-Western and London/South-Eastern regions (P = 0·01). These data provide an insight into the acid-generating potential of the diet in the British elderly population, which may have important consequences in this vulnerable group.

Mild metabolic acidosis, which can be caused by diet, may adversely affect cardiometabolic risk factors, possibly by increasing cortisol production. Methodologies for estimating diet-induced acid–base load using dietary-intake information have been established. To our knowledge, however, the possible association between dietary acid–base load and cardiometabolic risk factors has not been investigated. We cross-sectionally examined associations between dietary acid–base load and cardiometabolic risk factors in a free-living population. The subjects were 1136 female Japanese dietetic students aged 18–22 years. Dietary acid–base load was characterized as the potential renal acid load (PRAL), which was determined using an algorithm including dietary protein, P, K, Ca and Mg, as well as the ratio of dietary protein to K (Pro:K). Estimates of each nutrient were obtained from a validated comprehensive self-administered diet history questionnaire. Body height and weight, waist circumference and blood pressure were measured. Fasting blood samples were collected. After adjustment for potential confounding factors, higher PRAL and Pro:K (more acidic dietary acid–base loads) were associated with higher systolic and diastolic blood pressure (P for trend = 0·028 and 0·035 for PRAL and 0·012 and 0·009 for Pro:K, respectively). PRAL was also independently positively associated with total and LDL-cholesterol (n 1121; P for trend = 0·042 and 0·021, respectively). Additionally, Pro:K showed an independent positive association with BMI and waist circumference (P for trend = 0·024 and 0·012, respectively). In conclusion, more acidic dietary acid–base load was independently associated with adverse profile of several cardiometabolic risk factors in free-living young Japanese women.

Potassium (K) organic anion salts, such as potassium citrate or potassium malate in plant foods, may counteract low-grade metabolic acidosis induced by western diets, but little is known about the effect of other minor plant anions. Effects of K salts (chloride, citrate, galacturonate or tartrate) were thus studied on the mineral balance and digestive fermentations in groups of 6-week-old rats adapted to an acidogenic/5 % inulin diet. In all diet groups, substantial amounts of lactate and succinate were present in the caecum, besides SCFA. SCFA were poorly affected by K salts conditions. The KCl-supplemented diet elicited an accumulation of lactate in the caecum; whereas the lactate caecal pool was low in rats fed the potassium tartrate-supplemented (K TAR) diet. A fraction of tartrate (around 50 %) was recovered in urine of rats fed the K TAR diet. Potassium citrate and potassium galacturonate diets exerted a marked alkalinizing effect on urine pH and promoted a notable citraturia (around 0·5 μmol/24 h). All the K organic anion salts counteracted Ca and Mg hyperexcretion in urine, especially potassium tartrate as to magnesuria. The present findings indicate that K salts of unabsorbed organic anions exert alkalinizing effects when metabolizable in the large intestine, even if K and finally available anions (likely SCFA) are not simultaneously bioavailable. Whether this observation is also relevant for a fraction of SCFA arising from dietary fibre breakdown (which represents the major organic anions absorbed in the digestive tract in man) deserves further investigation.

These famous words by Mencken in the early 20th century about the meaning of life and death, may also apply to the struggle of the healthy skeleton against the deleterious effects of retained acid!’ ( Kraut & Coburn, 1994). The health-related benefit of a high consumption of fruit and vegetables and the influence of this food group on a variety of diseases has been gaining increasing prominence in the literature over a number of years. Of considerable interest to the osteoporosis field is the role that bone plays in acid–base balance. Natural, pathological and experimental states of acid loading and acidosis have been associated with hypercalciuria and negative Ca balance, and more recently the detrimental effects of ‘acid’ from the diet on bone mineral have been demonstrated. Suprisingly, consideration of the skeleton as a source of ‘buffer’ contributing to both the preservation of the body's pH and defence of the system against acid–base disorders has been ongoing for over three decades. However, it is only more recently that the possibility of a positive link between a high consumption of fruit and vegetables and indices of bone health has been more fully explored. A number of population-based studies published in the last decade have demonstrated a beneficial effect of fruit and vegetable and K intake on axial and peripheral bone mass and bone metabolism in men and women across the age-ranges. Further support for a positive link between fruit and vegetable intake and bone health can be found in the results of the Dietary Approaches to Stopping Hypertension (DASH) and DASH-Sodium intervention trials. There is now an urgent requirement for the implementation of: (1) fruit and vegetable and alkali administration–bone health intervention trials, including fracture risk as an end point; (2) reanalysis of existing dietary–bone mass and metabolism datasets to look specifically at the impact of dietary ‘acidity’ on the skeleton.