Currently, chronic noncommunicable diseases (CNDs) represent a public health problem, accounting for 70% of deaths in developing countries. The main CNDs are cardiovascular disease, cancer, chronic respiratory diseases and diabetes.1 Historically, an association has been reported between the feeding pattern and the development or progression of metabolic disorders and CNDs.2 In recent years one aspect that has received attention is the impact of the micronutrient profile on the maintenance of acid base equilibrium, describing the deleterious impact of metabolic acidosis (MA) on health status. The objective of the present review is to analyze the available evidence of the dietary acid load in different clinical conditions (Fig. 1).

Figure 1.

Complications of diets with high acid load. The chronic consumption of diets with high acid load favors the development of low grade AM, which is linked to metabolic abnormalities such as a decrease in bone mineral density and osteoporosis due to the activation of osteoclasts. In kidneys, MA causes an increase in urinary excretion of calcium, an increase in the reabsorption of citrate favoring the development of kidney stones, an increase in ammonium excretion and a decrease in uric acid excretion affecting the development and progression of the chronic kidney disease. Low-grade metabolic acidosis causes hypercortisolism, which decreases insulin sensitivity, with high risk of developing DM2 and nonalcoholic fatty liver. Decreases muscle anabolism and exacerbating the proteolytic state, putting the individual at greater risk of sarcopenia. The increase in Uric acid (UA), hypercortisolism and IR are considered risk factors for the development of hypertension. Independently, the acid load of the diet is associated with an increased cardiovascular risk. BMD: bone mineral density; AU: uric acid; IR: insulin resistance; DM2: diabetes mellitus type 2; HTN: hypertension; CNDs: chronic noncommunicable diseases; CVD: cardiovascular disease; ↑: increase; ↓: decrease.

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The organs involved in the maintenance of acid base balance are the lungs and kidneys, as well as a complex system of buffers (buffers). The interaction and proper function of these mentioned elements is required to maintain the arterial pH in optimal ranges (7.35–7.45). The condition where the pH value is less than 7.35 is called acidemia, and a value greater than 7.45 is called alcalemia. The main function of the lungs in acid–base homeostasis is the elimination of carbon dioxide (PaCO2). The kidneys reabsorb the filtered bicarbonate and maintain the production of bicarbonate (HCO3−) with the excretion of titrable and non-titratable acid, through the ammonium system (NH4+) in the urine. Metabolic acidosis (MA) is defined as the presence of an arterial pH<7.35 and/or decreased concentrations of HCO3−.3,4 The condition where the pH is very close to the lower limit (7.35) is called low-grade MA.5

Diet plays an essential role in the maintenance of acid base balance. Once the food is ingested, the stomach wall excretes hydrogen ion and the pancreas secretes alkali into the digestive tract. The gastrointestinal tract affects the acid–base state by absorbing sulfur amino acids and alkali salts, which will be transported as substrates to the liver and to metabolically active tissues. Once oxidized, the sulfur amino acids release protons and the organic acids release alkali, that will impact on the acid base reserve, being finally excreted by the kidneys. Although the intestine does not generate either acids or bases, the characteristics of the diet determine the formation of acids and alkalis once absorbed and metabolized in the liver.6

The dietary components that release acid precursors after metabolism are phosphorus and proteins (mainly the sulfur amino acids, such as cysteine, methionine and taurine, as well as cationic amino acids such as lysine and arginine). The nutrients precursors of alkali are potassium, magnesium and calcium.6

The kidneys eliminate the products from the metabolism of some anions (chlorine, phosphorus, sulphate), organic acids and cations (sodium, potassium, calcium, magnesium). If the amount of anions exceeds that of cations, a mechanism of urinary acid excretion (hydrogen ions H+) is stimulated. The total amount of acid excreted is called net acid production (NEAP) [(anionic+organic acids)−cations], which can be measured in the urine (direct NEAP) with the determination of ((NH4+ titicatable acid)−HCO3), or it can estimated through the dietary composition of the healthy individual (estimated NEAP). The amount of acids and alkalis that are produced according to the nutrient profile of the diet is called potential renal acid load (PRAL), this includes the amount of endogenously synthesized organic acids (estimated OA).7,8 There are 3 different ways to estimate the NEAP; Frassetto et al. proposed two equations to estimate the NEAP, which consider only the consumption of protein and potassium.9 Remer et al. proposed a mathematical model to estimate the PRAL which incorporates the amounts of micronutrients present in the regular diet of the individual, to which, by adding the estimated OA the stimated NEAP it is obtained. This same research group also proposed a model to estimate the PRAL that incorporates the amounts of micronutrients excreted in the urine, which we will called in the present work as urinary PRAL10 (Table 1).

The accuracy of the equations for estimating NEAP has not been studied in detail. Parmenter et al. reported a greater accuracy in the NEAP estimation by using the Remer T equations, observing a low accuracy using both equations proposed by Frassetto et al.; however, these calculations are frequently used in the literature.11

The concept of Potential renal acid load (PRAL) was coined by Remer and Manz in 1994, which reflects an estimate of the rate of intestinal absorption of various nutrients, the ion balance of calcium, magnesium and potassium, and the dissociation of phosphate at a pH of 7.4. The PRAL can be calculated for any food, categorizing them according to their capacity to release acids or bases to the circulation. Also the PRAL of the patient's diet can be studied by evaluating the daily consumption of the nutrients of interest. Diets with positive PRAL increase the production of acid precursors, while diets with negative PRAL increase the production of alkali precursors, that is, if the PRAL value for a type of food is <0, it is considered that such a food increases the alkalinity of the body fluids and, if PRAL>0, the food increases the production of acids in the body, with the corresponding impact on the acid–base state. In general, foods such as meat, eggs, cheese and whole grains have positive PRAL, while fruits and vegetables have negative PRAL. The PRAL of milk is considered neutral, as well as fats and sugars that have a small effect on the acid–base balance.10

The concept of PRAL has physiological bases and takes into account the chemical composition of foods (protein content, chloride, phosphorus, sodium, potassium, calcium and magnesium), the different rates of intestinal absorption of minerals and proteins with sulfur amino acids, as well as the amount of sulfates produced by protein metabolism.

Vegetable proteins have lower biological value as compared with proteins of animal origin. This is due to the proportion of cysteine and methionine, however, it is not considered that the protein of vegetable origin has a lower content of sulfurized amino acids for each gram of protein, so diets high in protein, regardless of type (animal or vegetable origin), tend to increase the PRAL.12

The consumption of a diet high in protein and phosphorus, low in potassium, calcium and magnesium, has an impact on long-term health, since these are considered acidogenic diets, that cause low-grade MA.17

One of the complications of low-grade MA is the increase in cortisol secretion and the decrease in its inactivation 18leading to hypercortisolism which increases the risk various metabolic disorders such as sarcopenia, insulin resistance, Type 2 diabetes mellitus and cardiovascular diseases, among others (Fig. 1).19 Epidemiological studies evaluating an association between acid load (PRAL, NEAP estimated or NEAPurinary) and the development of metabolic abnormalities are presented in the supplementary table.

Knowing the clinical implications of low grade MA, it is important to monitor the acid base balance through non-invasive methods. The measurement of urinary pH, obtained from a random sample, has been shown to be a good PRAL marker (β=−0.08, p<0.001). An alkaline urinary pH is associated with diets with negative PRAL68 even in patients with DM2 (r=−0.24, p=0.002), and it is shown that urinary pH values of less than 6.0 are associated with acidifying diets,69 Questionnaires for the quantification of dietary acid load are suggested for a subsequent implementation of dietary strategies.

The consumption of vegetable proteins versus proteins of animal origin could provide benefits. It has been shown and increase in urinary pH after 7 days on a vegetarian diet; the same effects are observed in patients after following this type of diet for only 2 or 3 days per week.70 The incorporation of dairy products (milk or yogurt) could help to cover for the protein intake without impacting the acid load, since they are foods with neutral PRAL,16 and the incorporation of fruits is inversely associated with the estimated NEAP, so the inclusion of this group of foods may reduce the acid load of the diet, however foods with high oxalate content should be avoided.71

The reduction in the consumption of industrialized products with phosphorus additives (carbonated beverages, industrialized teas, meats, frozen products and other products with food additives) may help to reduce the acid load.72

The routine consumption of mineral water or beverages with added bicarbonate has been shown to have beneficial effects in terms of increasing of urinary pH. These effects have been shown in the studies by Siener et al., that gave 1.4L of mineral water a day (3388mg/L of bicarbonate, 232mg/L of calcium and 337mg/L of magnesium)73; by Heil, who gave to drink mineral water rich in calcium, potassium, magnesium and selenium for 2 weeks74 and by Day et al. administering 1.5–1.8L/day of water enriched with 650mg/L of bicarbonate and 120mg/L of magnesium.75

In patients with CKD, an strategy to reduce MA is oral sodium bicarbonate supplementation, at a dose of 600mg/three times a day for 1 year, observing an increase in serum bicarbonate concentrations and a reduction in the decline in renal function in the supplemented group.76 This strategy has not been evaluated in low-grade MA not associated to CKD.

The PRAL calculation requires the use of a food frequency questionnaire or food diaries, for estimation of the relevant micronutrients consumption. In case of not having an appropriate software, it is suggested the inclusion of foods with neutral or negative PRAL, using PRAL tables for food portions (Table 2).

The evidence available of NEAP estimated and PRAL suggests a direct relationship with the development of metabolic complications, including an increase in muscle catabolism mediated by a decrease in insulin sensitivity, also decreasing muscle anabolism. These changes increase the loss of muscle mass in the elderly, and may influence the development of frailty and its complications.17,19,20

Diets with high acid load are associated with an increase in bone resorption, causing a decrease in bone density, however, the results of the studies are controversial, and authors used different indicators of acid load (urinary PRAL, PRAL in diet and estimated NEAP).28–31

Hypercortisolism and IR are risk factors for the development of HTN. In normotensive individuals there is a positive relationship between PRAL and NEAP with the values of systolic blood pressure.33,36,38,39 However the effect PRAL and NEAP on the incidence of HTN is controversial.37

Low-grade MA caused by diets with elevated PRAL and increased NEAP estimulate cortisol production, which causes IR through various mechanisms,42 and increases the risk of long-term DM2,44,45,48 In pregnant women, elevated PRAL and increased NEAP increases the risk of gestational diabetes mellitus (GDM) as reported in a case-control study.43

Diets with elevated PRAL and elevated NEAP could contribute to the development of nonalcoholic fatty liver, which may be explained by the increased release of fatty acids due to IR. Only 2 studies have evaluated this association with inconclusive results50,51

DM2 and HTN are main causes of CKD. Independently, the short and long term consumption of high acid load diets seems to have a negative impact on renal health by producing hyperfiltration to increase the excretion of acids.52 If maintained hyperfiltration favors the development of renal fibrosis and CKD53,55,56 with accelerated progression to ESRD.57 Renal lithiasis is another complication of low-grade MA, as the excretion of phosphorus and calcium in urine is increased, favoring the tubular reabsorption of citrate with a reduction in citrate excretion with the consequent change in urinary pH. These changes in urinary composition and pH increase the formation of calcium-oxalate and calcium-phosphate complexes, increasing the risk of kidney stones.62,63

The DM2, HTN and CKD increase cardiovascular risk and Acid load of the diet is a determinant of the three conditions. High PRAL and NEAP is associated with increased incidence of cardiovascular disease64 and high mortality rates both general and cardiovascular.67 However, regarding mortality, Huston et al. did not observe an association between acid load and greater risk of mortality.66

There is enough information regarding the long-term effects of diets with high acid load; however the publications on the impact of diet with low acid load or alkaline residue are scarce. The body's metabolic processes generate a significant load of hydrogen and there is always an active ventilatory compensation of blood pH; the alkaline intake through the diet does not seem to represent a mechanism to maintain alkalosis or any metabolic complication.

Some authors have suggested the implementation of vegetarian diets as a strategy to reduce metabolic acidosis. It is important to note that not only red meats or products of animal origin are the determinants of the acid load of the diet. It should be consider that these foods may be an important source of essential amino acids as described by Mafra et al.77 This type of vegetarian diets need professional supervision since it may compromise the intake of essential amino acids causing other pathologies and may affect protein anabolism.

According to the literature, the type of diet can profoundly affect the organism by providing acid precursors or bases. Diets with high acid load produces changes in the acid base balance. There is an association between low-grade metabolic acidosis with the development of chronic noncommunicable diseases. The implementation of strategies aiming to reduce the acid load of the diet through nutritional interventions may have a positive impact on health.

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  The micronutrient profile of the diet determines the production of acid and base precursors in the organism having an impact in the acid base balance.

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  The net production of acid may be estimated from the acid load of the diet using mathematical models that includes the consumption of calcium, magnesium, protein, phosphorus and potassium in the regular diet.

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  The consumption of diets with positive acid loads causes low-grade metabolic acidosis, which has been associated with the development of chronic diseases, such as diabetes, hypertension, chronic kidney disease, renal lithiasis and non-alcoholic fatty liver, among other.

No conflicts to declare.