Current guidelines on the management of arterial hypertension recommend lifestyle changes including dietary measures to prevent the development of high blood pressure (BP) and to assist in reducing BP as well as cardiovascular disease (CVD) risk in hypertensives [1
]. Apart from a reduction in salt and alcohol intake, increases in the consumption of fruits and vegetables, and vegetarian diets as well as Dietary Approaches to Stop Hypertension (DASH)-type diets have been shown to reduce BP in interventional and observational studies [2
]. Of note, a recent review and meta-analysis of dietary interventions for BP-reduction indicated that among common dietary interventions (including low-sodium diets), the DASH-type diet may be the most effective [4
]. Different aspects of the above-mentioned dietary patterns may account for the observed BP decreases. Apart from increased intakes of several minerals including potassium, for which substantial evidence for a BP-reducing effect exists [5
], a lowered nutritive proton load is a common characteristic of diets rich in fruits and vegetables, including DASH-type diets. Main determinants of the daily dietary acid load include high intakes of protein as well as phosphorus as acid-producing components, whereas high intakes of fruits, vegetables, and potatoes reduce the daily proton load. The potential renal acid load (PRAL) is an established marker of the diet-dependent proton load and has been used in several studies on different health outcomes in adults and children [7
]. Regarding the potential relationship of dietary acid load with BP, most [10
] but not all [14
] observational studies conducted in recent years suggest a corresponding direct link. Increases in dietary proton load have also been shown to induce changes in systemic acid–base status [16
] and different markers of such subclinical forms of metabolic acidosis have been related to BP and hypertension incidence as well [18
]. With respect to available mechanistic evidence, several animal models have linked disturbances in acid–base balance to (salt-sensitive) hypertension [21
], and these disturbances may already be present before the onset of hypertension [21
]. Also in humans, salt sensitivity of BP was associated with lower arterial pH [23
To elaborate on the potential BP-reducing mechanisms of plant-based diets, the aim of the current analysis was to assess the relation between diet-dependent acid load and BP as well as hypertension prevalence in a sample of the general adult population living in Germany, and to compare this association with the (established) relevance of potassium intake to BP, concurrently considering the possible confounding effects of sodium intake, kidney function, and several further risk factors for hypertension.
In our cross-sectional analyses in a comparably large representative sample of the general adult population living in Germany, we demonstrated that higher PRAL values, indicative of a higher diet-dependent proton load, are related to higher systolic BP and hypertension prevalence independent of estimated 24-h sodium excretion, BMI, eGFR, and several further established risk factors for elevated BP. Results were also confirmed in the subgroup not receiving antihypertensive treatment and in those participants with apparently normal kidney function. These findings are in line with several recent observational studies demonstrating similar direct associations between dietary acidity and BP or hypertension risk in cross-sectional [10
] and prospective [11
] analyses in different age groups. In two prospective studies in older adults with a mean baseline age of either 65 or 70 years, however, no consistent associations with hypertension incidence were seen for different markers of dietary acid load [14
]. The higher mean age in the study populations of these two studies may be one possible reason for the divergent findings, since BP seems to level off or even decreases in this age group [34
]. This may indicate that BP is less responsive to environmental influences such as dietary acid load at a higher age. Additionally, other predictors of hypertension such as chronic kidney disease or arterial stiffness may become more important in older individuals.
In addition to observational studies on dietary acid load and BP, there is also experimental evidence for a link between acid–base status and BP from animal studies, showing that disturbances in acid–base balance with lower systemic pH may precede the development of hypertension [21
]. A recent experimental study in humans also indicated that alkalinization may have an independent influence on BP: In the cross-over study of Conen et al. [36
], a clear BP-decrease was observed among overweight, middle-aged individuals after administration of alkalizing potassium citrate, whereas BP was not influenced by potassium chloride. A similarly designed study also comparing the BP-effects of potassium citrate and potassium chloride did however not confirm these results [37
]. The reasons for these conflicting findings are unclear, but differences in study duration, potassium citrate dose, and characteristics of the study populations such as antihypertensive medication use, especially of drugs influencing the potassium homeostasis, may have influenced the results.
Apart from the observed PRAL–BP associations, the present study also confirmed inverse associations of potassium intake with systolic and diastolic BP as well as hypertension prevalence in the DEGS1-population. Regarding the strength of these associations and the comparison with the PRAL–BP relation, our adjusted models (Table 2
) indicated that a 10-mmol higher estimated 24-h potassium excretion (corresponding to 0.4 g higher potassium intake) would result in a 0.3 mmHg lower systolic BP. According to our regression analyses, a similar systolic BP reduction would result from a PRAL reduction of about 6 mEq/day, broadly corresponding to 150 g higher vegetable intake or a 70 g lower meat intake. When considering the FFQ-based potassium intake estimate, a higher difference of about 0.8 g would be needed for a similar reduction in systolic BP. These comparisons indicate that in our analyses, the BP-association was stronger for the urinary than for the dietary estimates of potassium intake. However, when interpreting these predictions, it has to be kept in mind that our adjusted models explained only 10% to 20% of the BP variance, indicating a high interindividual variation due to unknown influencing factors. A possible reason for the difference between urinary and dietary estimates could be that the semi-quantitative FFQ used in DEGS1 may not allow for sufficiently detailed intake estimates to clearly separate the BP-effects of potassium from other possibly correlated but counteracting nutrients. Whether similar problems exist for the FFQ-based PRAL estimate cannot be determined in the present study due to missing urinary markers of diet-dependent acid load such as renal net acid excretion or 24-h urine pH. In general, the reported associations in the present analysis are only of moderate strength, which is largely due to the cross-sectional design (and the respective high inter-individual variation) of the DEGS1 study. With respect to potassium excretion, a recent large observational study in more than 100,000 adults reported a very similar decrease in systolic BP of 0.75 mmHg per each 1 g higher potassium excretion [38
Another point that needs discussion is that usually, a low PRAL diet is accompanied by a high potassium intake. Correspondingly, we found a significant inverse correlation of PRAL with both urinary biomarker- and FFQ-based estimated potassium intakes in the DEGS1 study population (data not shown). At least parts of the postulated PRAL effects on blood pressure could thus be potassium effects. Potassium intake has its own direct lowering effect on blood pressure and several mechanisms are discussed for this including a lowered sympathetic activity, an altered baroreceptor activity, and a reduced renin production as well as an increase of renal natriuresis [6
]. An additional postulated mechanism for BP-reduction with higher potassium intake is the vasodilating effect of this mineral [5
]. Since vascular tone is the main determinant of diastolic BP [39
], this mechanism may account at least partly for the differential associations of PRAL and potassium with diastolic and systolic BP observed in the present study.
Apart from the potassium-related effects, a variety of mechanisms have been proposed that suggest a potassium-independent influence of PRAL on blood pressure. The strong buffering of blood pH usually prevents clear changes in circulating free protons after marked increases in dietary acid loads, but this broadly constant pH level is not without a price. Increased glucocorticoid secretion is needed to facilitate ammoniagenesis, which in turn ensures renal elimination of excess H+
], thus preventing stronger blood pH reductions. In line with this it has been shown that reduction of dietary acid load by administration of alkali salts reduces glucocorticoid secretion in healthy nondiabetic [42
] and pre-diabetic subjects [36
]. Concurrently, elevated cortisol levels such as in subclinical hypercortisolism are frequently related to hypertension [44
]. Higher levels of serum uric acid (UA) may also partly explain a direct association of diet-dependent acid load with BP since higher UA levels are related to an increased hypertension risk [45
] and reduction of the dietary acid load has been shown to increase renal UA excretion and reduce serum UA in healthy young females [46
Moreover, also the influence of dietary acid load on gut microbiota and kidney function may mediate parts of the acid–base effects on blood pressure. The probable mechanisms are schematically represented in Figure 2
. In comparison to western diets with high acid loads, more alkaline diets rich in fruits and vegetables and rich in dietary fibers result in a different microbiome [47
] which may be more favorable with respect to BP [48
]. Regarding the association of dietary acid load with kidney function, several studies in recent years have suggested that a lower dietary acid load may contribute to a reduced incidence [49
] as well as slower progression [50
] of chronic kidney disease. It has been suggested that a higher acid load may be detrimental to renal health due to prolonged high intra-renal ammonia concentrations [51
]. Because a reduced kidney function may be related to higher BP-values already within the normal GFR-range, renal function represents a plausible link between dietary acid load and BP. In our analyses, however, adjustment for eGFR did not attenuate the observed associations of PRAL with systolic BP and hypertension prevalence. Moreover, our results were very similar after excluding participants with physician-diagnosed kidney impairment, microalbuminuria, or an eGFR < 60 mL/min/1.73 m2
(see Figure 1
). This is somewhat in contrast to the recent analyses of Akter et al. [13
], in which the association between dietary acid load and hypertension prevalence became non-significant after adjustment for eGFR.
Compared to some other studies examining the association between PRAL and BP outcomes [10
], the median PRAL of −3.4 mEq/day in the DEGS1-population seems rather low. However, comparable [14
] as well as much lower [52
] PRAL levels in other populations have also been reported. Whether these large differences in average PRAL values truly reflect the variance in daily proton load or are partly attributable to different dietary assessment methods or partly incomplete capturing of dietary intake with FFQ is currently unclear. Differences with respect to higher PRAL values observed in healthy children [12
] are at least partly explainable by coffee consumption since coffee has a negative (alkaline) PRAL of −1.7 mEq/100 g, and mean coffee intake in the DEGS1-population was almost 500 g/day, whereas it is negligible in most children.
Besides the potential benefit of a reduced PRAL with respect to BP, a lower dietary acid load has also been associated with a reduced incidence [49
] and progression [50
] of chronic kidney diseases as well as with a lower insulin resistance [53
] and a lower diabetes risk [9
]. At least theoretically, these different aspects could in combination contribute to a lowered cardiovascular risk with a more alkaline diet, but this hypothesis needs further investigation.
Several limitations of the present analysis need to be considered: First of all, the cross-sectional design of the DEGS1 study does not allow inferring a causal relationship between dietary acid load and BP. As has been mentioned above, the semiquantitative FFQ used in DEGS1 constitutes a further limitation. For the estimation of daily excretion of urinary sodium and potassium only spot urine samples were available. However, 24-h urine sampling is usually not feasible in large population-based studies and it has already been shown that the method of estimating 24-h excretion rates from spot urine mineral-creatinine ratios provides reasonable results within the DEGS1-population [54
]. Additionally, as has been addressed above, it has to be considered that potassium intake and the PRAL estimates are interrelated and no definitive separation on their BP-relevance can be obtained in an observational study. However, PRAL potentially reflects a broader dietary pattern compared to potassium intake alone. Differences between these dietary predictors are also supported by our findings of a more robust association of PRAL with systolic BP and hypertension prevalence, whereas potassium intake might be more relevant for diastolic BP. Strengths of the present analyses include detailed and standardized questionnaires and examinations in DEGS1 allowing for control of a large number of potential confounders of the investigated diet-BP associations. Moreover, to our knowledge, this is the first time that the relevance of dietary acid load for BP has been directly compared to the established BP-association of potassium in a large representative population sample.