Metabolic acidosis and cardiovascular risk: dietary acid, stroke, and heart attack

IN BRIEF

• Metabolic acidosis is a term indicating an acid-base imbalance; it is usually measured in clinical settings, but the dietary acid load (PRAL/NEAP) is also studied as a possible cardiometabolic risk factor.
• Observational studies show associations between a higher dietary acid load and certain cardiovascular risk factors (blood pressure, diabetes), but the causal relationship is not definitively established.
• Plausible biological mechanisms exist (endothelial dysfunction, inflammation, oxidative stress) that can link an acidic state with vascular processes; however, most evidence is observational or experimental in selected populations.
• Routine measurements (urine, serum bicarbonate) have limitations and are not diagnostic tools for predicting stroke or heart attack in the general population without clinical contextualization.

Abstract: What does science say?

Metabolic acidosis and dietary acid load have been proposed as factors that could influence cardiovascular health. Available evidence includes observational studies on large populations, systematic reviews, and some experimental attempts. These studies show associations between a higher acid load (estimated with indices such as PRAL or NEAP) and cardiometabolic risk factors — for example, hypertension and insulin resistance — and in some studies with mortality outcomes. Plausible biological mechanisms include endothelial alterations, inflammation, and metabolites such as homocysteine. However, most of the evidence does not demonstrate a direct causal link, and interpretive caution is still necessary: the effect may depend on the dose, the overall dietary profile, renal function, and contextual factors. Targeted clinical interventions are limited, and the results do not allow for general therapeutic recommendations; therefore, evaluation must remain individual and clinically guided.

What is metabolic acidosis and how is it assessed?

Metabolic acidosis is a condition in which the body's acid-base balance shifts towards increased acidity; in a clinical setting, it is diagnosed with blood tests (arterial pH, bicarbonates, anion gap). In parallel, there is the notion of "dietary acid load": an index that estimates how much the diet tends to produce acids or bases once metabolized. The most common method to estimate this effect is PRAL (Potential Renal Acid Load), developed to quantify the ability of foods to determine renal secretion of acids or bases [1].

PRAL and NEAP are calculated based on nutrient intake (proteins, potassium, calcium, magnesium, phosphorus) and provide a theoretical value of the dietary acid-base balance: more positive values indicate a greater acidifying potential, negative values indicate a more alkalizing effect. It is important to emphasize that these indices estimate a dietary trend and do not replace clinical measurements of pH or serum bicarbonate, which are affected by many other metabolic and renal factors [1].

Epidemiological Evidence: What Observational Studies Show

Several observational studies have investigated the relationship between dietary acid load and cardiovascular risk factors. An analysis based on the South Korean population (KNHANES) highlighted that higher PRAL/DAL scores were associated with a greater estimated 10-year risk of cardiovascular events, independently of obesity and insulin resistance [2].

A systematic review and meta-analysis of observational studies synthesized the available data and found associations between a higher dietary acid load and certain cardiometabolic factors, particularly blood pressure, although relationships with lipids and glycemia were more heterogeneous [3].

Prospective and cohort studies have also linked higher acid load values to an increased risk of hypertension in different populations; for example, the Rotterdam Study reported an association between dietary acidity indices and incidental risk of hypertension [4], while data from large cohorts (Nurses' Health Study) indicate an increased risk of hypertension with higher NEAP [5].

These results suggest that there is a correlation between a more acidifying diet and certain risk factors for stroke and heart attack, but these are mostly observational data: therefore, they do not prove a causal relationship and may be influenced by confounders (overall diet quality, lifestyle, kidney function) [2][3][4][5].

Plausible biological mechanisms

The biological plausibility of the link between an acidic state and vascular damage is based on multiple experimental and clinical pathways. Under conditions of local or systemic acidosis, alterations are observed that can promote inflammation, endothelial dysfunction, and oxidative stress, all processes involved in atherogenesis and the destabilization of atherosclerotic plaque [6].

Endothelium, inflammation, and oxidative stress

In vitro experiments and experimental models show that a lower pH environment can increase the expression of adhesion molecules and pro-inflammatory cytokines on endothelial cells, facilitating leukocyte adhesion and vascular permeability, relevant aspects for the formation and progression of atherosclerotic plaque [6]. Clinical studies in patients with metabolic acidosis (for example, in chronic kidney failure) document signs of worsening vascular function that improve, in some cases, with the correction of acidosis [9].

Homocysteine, thrombosis, and mortality

Metabolic markers associated with unfavorable metabolic states, such as homocysteine, have been correlated with an increased risk of cardiovascular events in large population cohorts. Research from the Hordaland Homocysteine Study has shown that high homocysteine levels are linked to a more unfavorable cardiovascular risk profile and higher rates of hospitalization for cardiovascular diseases in the studied population [7][8]. These data are consistent with the hypothesis that certain metabolic alterations related to nutritional status can interact with vascular processes.

What it means in practice

For the general public, evidence does not support simplified claims such as "acidosis causes heart attack/stroke." However, it is reasonable to consider the acid load of the diet as one element of the overall nutritional picture: diets rich in fruits, vegetables, fiber, and with moderation of animal products and processed foods tend to produce a favorable nutritional balance and are correlated with a lower cardiovascular risk in studies examining broader dietary patterns [2][3].

For patients with chronic kidney disease or conditions that affect acid-base balance, clinical evaluation and eventual treatment (for example, with alkali in a specialized setting) must be decided by a physician. Intervention studies on selected populations suggest that correcting acidosis can improve some indicators of vascular function in people with kidney failure, but these results do not automatically translate into recommendations for the general population [9].

In summary: prioritizing a vegetable-rich diet, maintaining regular physical activity, and controlling blood pressure, glycemia, and lipids remain the measures with the most evidence for preventing stroke and heart attack. The topic of acid load may be relevant as part of the overall dietary profile, but it is not a single determining factor.

Key points to remember

• The acid load of the diet (PRAL/NEAP) is associated with various cardiometabolic risk factors in observational studies, especially hypertension and insulin resistance. [2][3]
• Plausible mechanisms exist (endothelial dysfunction, inflammation, oxidative stress), but direct evidence of causality is still lacking. [6][9]
• Metabolic markers such as homocysteine are associated with cardiovascular risk in large cohorts; this does not prove that lowering these markers automatically reduces events. [7][8]
• Clinical measures of pH and bicarbonate are meaningful only in a medical context: the general population should not base therapeutic choices on home urinary/salivary pH tests without consultation. [1][9]

Limitations of the Evidence

Most research on the link between acidosis, acid load, and cardiovascular disease is observational. Cohort and cross-sectional studies can highlight associations but not establish causality: results can be influenced by confounding factors (general diet quality, physical activity, smoking, kidney status, socioeconomic status). [2][3]

PRAL and NEAP indices are useful estimates but do not directly measure blood or tissue pH; furthermore, individual response depends on kidney function and other metabolic processes. Improper measurements (urine or saliva test strips) are also subject to interpretation errors and do not replace clinical evaluations. [1]

Intervention studies evaluating the effect of alkalization on stroke or heart attack prevention in the general population are scarce. Some trials in populations with kidney failure suggest benefits on vascular markers, but remain limited in size, duration, and generalizability. [9]

Editorial Conclusion

The topic of metabolic acidosis and dietary acid load is a growing area of research that raises relevant questions for cardiovascular prevention. Evidence suggests consistent associations with the hypothesis that a diet rich in acidifying foods may increase certain risk factors (blood pressure, insulin resistance) and, in some studies, be associated with an increased risk of cardiovascular disease. However, the convergences are not sufficient to define a cause-and-effect relationship independent of other dietary and lifestyle factors.

For readers: consider acid load as one nutritional indicator among many, not as a sole explanation for stroke or heart attack. Strategies with stronger evidence remain a balanced diet (abundance of fruits and vegetables), physical activity, control of blood pressure, cholesterol, and diabetes, and personalized medical advice in clinical cases. New research, particularly well-designed intervention trials, is needed to assess whether modifying the dietary acid-base balance concretely reduces cardiovascular events.

Editorial Note

This article was originally published in the past and updated according to scientific and informative criteria. Informational purpose: it does not replace the advice of your treating physician. If you have relevant clinical conditions (kidney failure, metabolic disorders, pharmacological therapies), consult your specialist before undertaking dietary or therapeutic changes.

SCIENTIFIC RESEARCH

1. Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc. 1995;95(7):791–797. https://doi.org/10.1016/S0002-8223(95)00219-7
2. Han E, Kim G, Hong N, Lee YH, et al. Association between dietary acid load and the risk of cardiovascular disease: nationwide surveys (KNHANES 2008–2011). Cardiovasc Diabetol. 2016;15:122. https://doi.org/10.1186/s12933-016-0436-z
3. Haghighatdoost F, et al. Dietary acid load and cardiometabolic risk factors: a systematic review and meta-analysis of observational studies. Public Health Nutr. 2019;22(15):2823–2834. https://doi.org/10.1017/S1368980019001125
4. Engberink MF, Bakker SJ, Brink EJ, van Baak MA, van Rooij FJ, Geleijnse JM. Dietary acid load and risk of hypertension: the Rotterdam Study. Am J Clin Nutr. 2012;95(6):1438–1444. https://doi.org/10.3945/ajcn.111.022343
5. Forman JP, et al. Diet-dependent net acid load and risk of incident hypertension in United States women. Hypertension. 2009;54(4):751–755. https://doi.org/10.1161/HYPERTENSIONAHA.109.135582
6. Zünd G, Uezono S, Stahl GL, et al. Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. Am J Physiol Cell Physiol. 1997;273(5):C1571–C1580. https://doi.org/10.1152/ajpcell.1997.273.5.C1571
7. Nygård O, Vollset SE, Refsum H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA. 1995;274(19):1526–1533. https://doi.org/10.1001/jama.1995.03530190040032
8. Nurk E, Tell GS, Vollset SE, et al. Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study. Arch Intern Med. 2002;162(12):1374–1381. https://doi.org/10.1001/archinte.162.12.1374
9. Kendrick J, et al. Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study. Clin J Am Soc Nephrol. 2018;13(10):1463–1470. https://doi.org/10.2215/CJN.00380118
10. Mansour D, et al. Serum Bicarbonate Concentration and Cause-Specific Mortality: The National Health and Nutrition Examination Survey 1999–2010. Mayo Clin Proc. 2019;94(1):42–53. https://doi.org/10.1016/j.mayocp.2019.05.036