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Dietary acid load and risk of cardiovascular disease: a prospective population-based study

BMC Cardiovascular Disorders volume 21, Article number: 432 (2021) Cite this article

Abstract

Background and aim

Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid–base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study.

Materials and methods

Participants (n = 2369) free of CVD at baseline (2006–2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores.

Results

Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32–0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs.

Conclusions

This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population.

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Introduction

The acid–base balance within the body can be influenced by eating patterns and the acid load of the diet [1]. Animal-based food products raise the acidifying potentials of diets [2, 3] and negatively manipulate the metabolic and physiologic status [4]. The acidic dietary patterns have become prevalent within the global dietary transition [5], which may be a risk factor for the development of metabolic and cardiovascular diseases (CVDs).

Potential Renal Acid Load (PRAL) [6] and Net Endogenous Acid Production (NEAP) [7] are common and valid indicators of dietary acid load and overall nutritional quality of a diet [6, 7]. The PRAL score is comprised of dietary magnesium, potassium, phosphorus, calcium, and protein [7], and NEAP formula is based on dietary intake of protein and potassium [8]. Both scores are associated with the prevalence of type 2 diabetes [9, 10] and hypertension [11,12,13,14]. PRAL alone is linked to the incidence of insulin resistance [15, 16], metabolic syndrome [17], and progression of chronic kidney disease [18, 19].

Observational and epidemiological studies have reported inconsistent results on dietary acid load, and CVD outcomes [12, 14, 20, 21]. PRAL and CVD mortality were positively associated among Swedish individuals [22] and inversely related among the Japanese population [23]. In contrast, no significant association was detected between dietary acid load and CVD incidence among the Polish [24] and Dutch [12] populations. Meanwhile, the majority of the findings confirm the detrimental impacts of acidic dietary patterns on health [14, 17], which is mostly related to the increased tissue metabolic acidosis [25], changes in the glycemic [16, 26, 27] and lipid profiles [28] and, increased blood pressure [12, 13, 29].

Inadequate and inconsistent results bring unclear findings and challenge the documentation of standard global dietary guidelines. Here, we aimed to evaluate whether dietary acid load, defined as PRAL and NEAP scores, could be a predictor of CVD risk in the framework of a population-based study among an Asian population.

Methods

Study population

This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS), a population-based study that aims to investigate non-communicable diseases (NCDs) within a representative sample of Iranians from district 13 of Tehran. The TLGS was initiated in 1999 and includes repeated measurements at 3-year intervals [30]. In total, 3678 men and women (aged ≥ 19) with complete demographic, anthropometric, biochemical, and dietary data, who have participated in the third TLGS examination (2006–2008), were recruited. Participants were excluded if they aged out of the predefined limit (70 < x < 19 years old; n = 626), and had misreported energy intake (4200 < x < 800 kcal/day; n = 579) and CVD history at baseline (myocardial infarction (MI), stroke, angina, coronary revascularization; n = 90). Participants were also excluded if they left the study within the follow-up period (n = 14). Finally, 2369 adults (1030 men and 1339 women) were included in the analyses (Fig. 1) [30, 31].

Fig. 1
figure 1

Flowchart of the study population

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All participants have provided written consents at baseline. The study protocol complied with the 1975 Ethical Guidelines of the Helsinki Declaration and was approved by the Ethics Research Council of the Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences.

Demographic and anthropometric measurements

Trained interviewers have collected demographic information using pretested and standardized questionnaires [31]. Weight was recorded to the nearest 100 g by digital scales, while participants had light clothing. Height was measured to the nearest 0.5 cm, standing without shoes, using a drop-down tape-meter. Body mass index (BMI) was calculated by the division of weight (kg) by the square of height (m2). Waist circumference measurement was taken to the nearest 0.1 cm, midway between the lower border of the ribs and the iliac crest, while participants were minimally dressed by a soft measuring tape. Systolic (SBP) and diastolic blood pressures (DBP) were measured twice on the right arm using a standardized mercury sphygmomanometer; the mean of the two measurements was considered as the final blood pressure of the participants [31]. The frequency and duration of physical activity (expressed as metabolic equivalent hours per week; MET-h/wk) was assessed by a Modifiable Activity Questionnaire (MAQ) [32].

Biochemical measurements

Baseline and follow-up blood samples were taken from all participants following a 12–14 h fasting. Triglyceride (TG) level was assayed by enzymatic colorimetric method with glycerol phosphate oxidase. Fasting serum glucose (FSG) was determined using enzymatic colorimetric analysis and glucose oxidase. High-density lipoprotein cholesterol (HDL-C) measurement was obtained after precipitation of the apolipoprotein-B-containing lipoproteins with phosphotungstic acid. The Pars Azmoon kits (Pars Azmoon Inc., Tehran, Iran) and Selectra 2 auto-analyzers (Vital Scientific, Spankeren, Netherlands) were used to perform the analyses.

Dietary assessment

Demographic, dietary, anthropometric, and biochemical data were obtained from all participants at baseline (2006–2008). Trained interviewers used a 168-item semi-quantitative Food Frequency Questionnaire (FFQ) at the first examination to assess participants' dietary intake over the past year. The reliability, comparative validity and, stability of the questionnaire were previously evaluated in a random sample and proven to be reasonable [33].

The participant’s consumption frequency of each food item was recorded on a daily, weekly, or monthly basis [31], and the household-measured portion sizes were converted to grams. The energy and nutrient content analysis of raw food and beverages was based on the US Department of Agriculture Food Composition Table (USDA FCT). Since the Iranian Food Composition Table has limited nutritional data, it was only used for the traditional items not listed within the USDA FCT [34].

Dietary acid load calculation

In this study, the dietary acid–base load was assessed by two indexes of PRAL and NEAP, using the following formula [7, 8]:

$$\begin{aligned} & {\text{PRAL }}\left( {{\text{mEq/d}}} \right) = \left[ {{\text{protein}}\left( {{\text{g/d}}} \right) \times 0.{49}} \right] \\ & \quad + \left[ {{\text{phosphorus}}\left( {{\text{mg/d}}} \right) \times 0.0{37}} \right] - \left[ {{\text{potassium}}\left( {{\text{mg/d}}} \right) \times 0.0{21}} \right] \\ & \quad - \left[ {{\text{calcium }}\left( {{\text{mg/d}}} \right) \times 0.0{13}} \right] - \left[ {{\text{magnesium }}\left( {{\text{mg/d}}} \right) \times 0.0{26}} \right] \\ \end{aligned}$$
$${\text{NEAP}}\left( {{\text{mEq/d}}} \right) = \left[ {{54}.{5} \times {\text{protein}}\left( {{\text{g/d}}} \right)/{\text{potassium }}\left( {{\text{mEq/d}}} \right)} \right]{-}{1}0.{2}$$

Dietary PRAL is a validated proxy for renal net acid excretion [1, 8], and the NEAP score is defined as the total nonvolatile acid load that results from endogenous acid production and gastrointestinal absorption [35]. A diet with acidifying potentials has higher PRAL and NEAP scores [4, 29]. There is a large variation in dietary acid load within the countries. The mean score of PRAL ranged from − 23.0 mEq/day in France [26] to − 22.0 mEq/day in Iran [18], − 21.8 mEq/day in Korea [14], − 14.6 mEq/day in Netherland [12], 10.4 mEq/day in Japan [11], and 22.1 mEq/day in China [37]. Likewise, mean dietary NEAP score ranged from 86.8 mEq/day in China [36], to 32.6 mEq/day among American children [6], and 31.5 mEq/day in France [26]. Both PRAL and NEAP were calculated using residual energy-adjusted nutrient intake data from the FFQs.

Definition of terms

Diabetes was defined as FSG over 126 mg/dL, 2-h serum glucose above 200 mg/dL or use of anti-diabetic medications [37]. Hypertension was explained as SBP above 140 mm Hg, DBP higher or equal to 90 mm Hg, or concurrent use of antihypertensive medications [33].

Definition of outcomes

Details of the collection of CVD-related data have been described elsewhere [31]. The CVD terminology was primarily defined as CHD-related events, stroke (a new neurological deficit that took ≥ 24 h), or CVD death (definite fatal stroke, definite fatal CHD, and definite fatal MI) [38]. CHD-related outcomes were including definite or probable MI, and angiographic-approved CHD [39].

In the current study, participants were followed up annually by telephone calls, and a trained nurse or a physician collected the required information on possible medical events. Further information was extracted from the medical records. The collected data were reviewed by an adjudication committee, which included a physician, an internist, an epidemiologist, a cardiologist, an endocrinologist, and associate external experts as needed. The final diagnosis was reported by a predefined coding protocol [40].

Statistical analysis

In this study, IBM SPSS (SPSS Inc., Chicago, IL, USA, version 20.0) was used to perform the analyses, and P-values ≤ 0.05 were statistically significant. Mean (SD) values of the baseline characteristics of participants with and without CVD were compared by independent t-test. The chi-square test was used to compare frequencies (%) between two groups. Dietary intake of participants were compared across tertiles of PRAL and NEAP using analysis of variance (ANOVA) test. A univariate analysis was conducted for each potential confounder, and variables with PE < 0.2 were included in the multivariable model; total dietary energy, and total dietary fat were included in the final model and the physical activity was eliminated. Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and the 95% confidence intervals (CIs) of dietary acid load and CVD events, and person-year was considered as the underlying time metric. Time to event was defined as the time to the onset of an event, or time to the end of follow-up.

Three Cox proportional hazards regression models were identified across tertiles of PRAL and NEAP; model 1 was adjusted for sex, age and smoking status, and model 2 was further adjusted for energy intake (kcal/d) and total fat intake (g/d). The median value of each dietary tertile was used to assess the overall HR trends in the Cox proportional hazard regression model.

Results

Mean age and BMI of participants were 38.5 ± 12.7 years and 26.6 ± 4.8 kg/m2 at baseline, respectively, and 43.5% were men. During an average follow-up period of 6.7 ± 1.4 years, 79 participants experienced CVD events (3.3%), and angiographic proven CVD, definite MI, unstable angina, and stroke were the most common outcomes.

Table 1 represents the distribution of major CVD risk factors and biochemical variables for participants with and without CVD events. Participants with CVD events were older (P = 0.001). Diabetes (13.2 vs. 3.7%, P = 0.001) and hypertension (42.1 vs. 9.4%, P = 0.001) were more prevalent among incident cases compared to the rest of the cohort. Also, a higher percentage of subjects with CVD events were current smokers (20.2 vs. 11.7%, P = 0.02).

Table 1 Baseline characteristics of the participants: Tehran Lipid and Glucose Study (TLGS)
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Dietary intakes of participants across tertiles of PRAL and NEAP are reported in Table 2. Mean dietary PRAL and NEAP were − 11.1 ± 18.6 mEq/day and 35.9 ± 10.9 mEq/day, respectively. Range of PRAL score across tertiles was < − 16.7 mEq/day, − 16.7 to − 2.45 mEq/day, and > − 2.45 mEq/day. Range of NEAP was < 30.6 mEq/day, 30.6–39.3 mEq/day, and > 39.3 mEq/day, in the first, second and third tertile, respectively. Participants in the lowest tertiles of PRAL had higher intakes of total dietary fiber, calcium, potassium, magnesium, potato, fruits and vegetables, and lower consumption of animal meat, cheese, grains and rice (P for all < 0.001). Similarly, lower NEAP score was related to lower consumptions of animal meat, cheese, grains and rice, and higher intakes of dietary fiber, calcium, potassium, magnesium, potato, and fruits and vegetables (P for all < 0.001).

Table 2 Dietary intake of participants across tertiles of PRAL and NEAP: Tehran Lipid and Glucose Study (TLGS)
Full size table

The hazard ratio (95% CI) of CVD incidence across tertile categories of PRAL and NEAP are shown in Table 3. The risk of CVD events was reduced significantly in the NEAP crude model (HRs = 0.50; CI 0.32–0.96; P trend = 0. 032). No significant associations were observed for PRAL and NEAP scores and CVD incidence after adjusting for age, sex, and smoking status in the second model, and total energy and total fat intake in the third model.

Table 3 Hazard ratio (95% CI) of cardiovascular disease across tertiles of PRAL and NEAP: Tehran Lipid and Glucose Study (TLGS)
Full size table

Discussion

In this population-based cohort study, we assessed the potential associations between dietary acid load and CVD outcomes. After adjusting for potential confounders, no significant associations were observed for PRAL and NEAP and CVD incidence risk, which may be explained by the low number of CVD cases, relatively short follow-up period, young study population, and potential changes in the dietary patterns of participants over time.

Our findings, however, were in line with the results of a large-scale study in Poland [21]. In contrast, a 2016 cross-sectional study on Korea National Health and Nutrition Examination data reported a positive association between the dietary acid load and incidence risk of CVD [14]. The higher dietary acid load has also elevated the risk of CVD mortality among Japanese individuals [23], increased 10-year mortality of patients with coronary artery bypass surgery in Iran [41] and, influenced the likelihood of chronic peripheral arterial disease among Americans [42]. Indeed, various populations differ in baseline characteristics and habitual dietary intakes, composing a dietary acid load spectrum [11, 21].

Previous publications have reported associations between the dietary acid load and CVD risk factors [11, 29, 43,44,45,46]. Dietary acidity induces low-grade acidosis that is linked to the development of metabolic complications, including diabetes [47], hypertension, and renal and bone complications [19, 48, 49]. PRAL and NEAP scores were both positively associated with serum TG levels [43]. PRAL was also independently associated with increased TG, SBP [44], and low-density lipoprotein cholesterol (LDL) [11] levels, and inversely related to fasting blood glucose [44]. In a 2018 systematic review and meta-analysis, a non-linear association was observed between NEAP and hypertension, and a 20-unit increase in PRAL value raised the risk of hypertension by 3% [45]. Furthermore, one study in South China highlighted the gender-dependent hypotensive properties of PRAL, which appeared insignificant in the context of NEAP [29]. A recent meta-analysis found positive associations between PRAL scores and SBP, DBP, insulin concentrations, and diabetes [50]. In contrast, no cross-sectional or longitudinal associations were observed between dietary acid load and various blood pressure indices in Swedish middle-aged men [51], metabolic syndrome risk factors [52], and risk of hypertension in older Dutch adults [12].

The mean dietary PRAL and NEAP in this study were − 11.1 ± 18.6 mEq/day and 35.9 ± 10.9 mEq/day, respectively, which confirms the dietary pattern of our population to be less acidic comparing to the Korean (PRAL: − 21.8 mEq/day) [14] and French (PRAL: − 23.0 mEq/day) [26] populations. Nevertheless, the dietary patterns of Chinese (PRAL: 22.1 mEq/day) [29] and Japanese (10.4 mEq/day) populations [11] appeared to be more alkalizing. This study was conducted on Iranian adults with transitional dietary patterns and an estimated animal-to-plant protein ratio of approximately 1.3–2.1.4 [53].

Participants with lower values of PRAL and NEAP scores had lower intakes of animal products and higher intakes of fruits and vegetables. It is generally confirmed that animal-based food items hold acidifying properties [3], whereas plant-food sources are more alkalizing [54]. Western dietary patterns, with an average 15–17% of energy from animal protein, are major acid suppliers to the body [2, 3]. On the contrary, the Dietary Approach to Stop Hypertension (DASH) pattern that is mainly comprised of plant foods and monounsaturated and polyunsaturated fats substantially reduces the dietary acid load (NEAP; 31 mEq/day vs. 78 mEq/day) [55]. Inadequate consumption of low-potassium fruit and vegetables in large samples of American individuals had adverse effects on the dietary acid load [3]. The dietary potassium of vegetables can bind to organic anions and metabolize to bicarbonate, which is ultimately capable of reducing NEAP [46]. The total or partial replacement of low-nutrient and energy-dense food items with fruits and vegetables can reduce the overall NEAP regardless of the amount of protein required [56].

To date, mechanistic information linking dietary acid load and CVD outcomes is mostly attributed to the role of chronic metabolic acidosis and hypertension. High adherence to Western dietary patterns enhances metabolic acidosis, and in return, increases the production of cortisol, ammoniagenesis, and renal acid excretion [6, 57]. Together, this leads to the diagnosis of hypertension [6]. In addition, restrictions in the dietary intake of potassium can affect the vascular vasodilation and damage blood vessels, and result in intracellular potassium deficiencies and compensatory sodium gains into the cell for the maintenance of the tonicity and volume [57]. Other mediators of metabolic acidosis and hypertension are the reduced excretion of citrate, increased release of calcium and cortisol, and the quality and quantity of the dietary protein [48]. High dietary acid load and chronic metabolic acidosis are also closely linked to the reduced affinity of the insulin to its receptor, increased risk of insulin resistance, and subsequently, hyperglycemia [15,16,17]. CVD can be autonomously promoted from insulin resistance through various pathways, including coronary microcirculatory dysfunction [58] and increased arrhythmogenesis [59].

This study has a number of strengths, including the high follow-up rate in the framework of a prospective population-based design, and the use of a validated FFQ for the assessment of habitual dietary intakes. The use of dietary PRAL for the measurement of dietary acid–base balance is one of the main limitations of this study. Although PRAL and NEAP scores have been widely used in previous publications, they are measured indirectly from the FFQs and can be influenced by inaccurate dietary reports [6, 7]. Also, the variations in the dietary patterns over time, the actual nutrient composition of specific meals, the preparation methods, and the nutrients’ absorption within the gastrointestinal tract are not considered by the PRAL and NEAP equations. Moreover, the low rate of CVD events in our population could have led to underestimations in CVD incidence. Lastly, the relatively short follow-up period with a relatively young population made it difficult to follow CVD endpoints.

Conclusion

Our results did not show any significant associations between dietary acid load and risk of CVDs within a representative sample of Iranians. The global growth in CVDs prevalence, the high treatment costs and burden of CVDs, and the critical role of diet in cardiovascular health call for investigations on dietary acid load and CVDs risk, with larger-scale samples and longer follow-up durations.

Availability of data and materials

The database used and/ or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

BMI:

Body mass index

CHD:

Coronary heart disease

CVD:

Cardiovascular disease

DBP:

Diastolic blood pressure

FFQ:

Food frequency questionnaire

FSG:

Fasting serum glucose

HDL-C:

High-density lipoprotein cholesterol

LDL:

Low-density lipoprotein cholesterol

NCDs:

Non-communicable diseases

NEAP:

Net endogenous acid production

PRAL:

Potential renal acid load

SBP:

Systolic blood pressure

TC:

Total cholesterol

TG:

Triglyceride

TLGS:

Tehran lipid and glucose study

References

  1. Scialla JJ, Anderson CA. Dietary acid load: a novel nutritional target in chronic kidney disease? Adv Chron Kidney Dis. 2013;20(2):141–9.

    Article  Google Scholar 

  2. Asghari G, Mirmiran P, Hosseni-Esfahani F, Nazeri P, Mehran M, Azizi F. Dietary quality among Tehranian adults in relation to lipid profile: findings from the Tehran Lipid and Glucose Study. J Health Popul Nutr. 2013;31(1):37.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Smit E, NIETO FJ, Crespo CJ, Mitchell P. Estimates of animal and plant protein intake in US adults: results from the Third National Health and Nutrition Examination Survey, 1988–1991. J Am Diet Assoc. 1999;99(7):813–20.

  4. Manz F. History of nutrition and acid-base physiology. Eur J Nutr. 2001;40(5):189–99.

    Article  PubMed  CAS  Google Scholar 

  5. Azizi F, Ghanbarian A, Momenan AA, Hadaegh F, Mirmiran P, Hedayati M, et al. Prevention of non-communicable disease in a population in nutrition transition: Tehran lipid and glucose study phase II. Trials. 2009;10(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Remer T, Dimitriou T, Manz F. Dietary potential renal acid load and renal net acid excretion in healthy, free-living children and adolescents. Am J Clin Nutr. 2003;77(5):1255–60.

    Article  PubMed  CAS  Google Scholar 

  7. Frassetto LA, Todd KM, Morris RC Jr, Sebastian A. Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr. 1998;68(3):576–83.

    Article  PubMed  CAS  Google Scholar 

  8. Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59(6):1356–61.

    Article  PubMed  CAS  Google Scholar 

  9. Mangano KM, Walsh SJ, Kenny AM, Insogna KL, Kerstetter JE. Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium. J Bone Min Res. 2014;29(2):500–6.

    Article  CAS  Google Scholar 

  10. Emamat H, Tangestani H, Bahadoran Z, Khalili-Moghadam S, Mirmiran P. The associations of dietary acid load with insulin resistance and type 2 diabetes: a systematic review of existing human studies. Recent Pat Food Nutr Agric. 2019;10(1):27–33.

    Article  PubMed  CAS  Google Scholar 

  11. Murakami K, Sasaki S, Takahashi Y, Uenishi K. Association between dietary acid–base load and cardiometabolic risk factors in young Japanese women. Br J Nutr. 2008;100(3):642–51.

    Article  PubMed  CAS  Google Scholar 

  12. Engberink MF, Bakker SJ, Brink EJ, van Baak MA, van Rooij FJ, Hofman A, et al. Dietary acid load and risk of hypertension: the Rotterdam Study. Am J Clin Nutr. 2012;95(6):1438–44.

    Article  PubMed  CAS  Google Scholar 

  13. Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and risk of incident hypertension in United States women. Hypertension. 2009;54(4):751–5.

    Article  PubMed  CAS  Google Scholar 

  14. Han E, Kim G, Hong N, Lee Y-h, Kim DW, Shin HJ, et al. Association between dietary acid load and the risk of cardiovascular disease: nationwide surveys (KNHANES 2008–2011). Cardiovasc Diabetol. 2016;15(1):1–14.

  15. Moghadam SK, Bahadoran Z, Mirmiran P, Tohidi M, Azizi F. Association between dietary acid load and insulin resistance: Tehran Lipid and Glucose Study. Prevent Nutr Food Sci. 2016;21(2):104.

    Article  CAS  Google Scholar 

  16. Emamat H, Tangestani H, Bahadoran Z, Khalili-Moghadam S, Mirmiran P. The associations of dietary acid load with insulin resistance and type 2 diabetes: a systematic review of existing human studies. Recent Patents Food Nutr Agric. 2019;10(1):27–33.

    Article  CAS  Google Scholar 

  17. Maalouf NM, Cameron MA, Moe OW, Adams-Huet B, Sakhaee K. Low urine pH: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol. 2007;2(5):883–8.

    Article  PubMed  CAS  Google Scholar 

  18. Mirmiran P, Yuzbashian E, Bahadoran Z, Asghari G, Azizi F. Dietary acid-base load and risk of chronic kidney disease in adults: Tehran lipid and glucose study. Iran J Kidney Dis. 2016;10(3):119–25.

    PubMed  Google Scholar 

  19. Kanda E, Ai M, Kuriyama R, Yoshida M, Shiigai T. Dietary acid intake and kidney disease progression in the elderly. Am J Nephrol. 2014;39(2):145–52.

    Article  PubMed  CAS  Google Scholar 

  20. Akter S, Eguchi M, Kurotani K, Kochi T, Pham NM, Ito R, et al. High dietary acid load is associated with increased prevalence of hypertension: the Furukawa Nutrition and Health Study. Nutrition. 2015;31(2):298–303.

    Article  PubMed  CAS  Google Scholar 

  21. Kucharska AM, Szostak-Węgierek DE, Waśkiewicz A, Piotrowski W, Stepaniak U, Pająk A, et al. Dietary acid load and cardiometabolic risk in the Polish adult population. Adv Clin Exp Med. 2018;27(10).

  22. Xu H, Åkesson A, Orsini N, Håkansson N, Wolk A, Carrero JJ. Modest U-shaped association between dietary acid load and risk of all-cause and cardiovascular mortality in adults. J Nutr. 2016;146(8):1580–5.

    Article  PubMed  CAS  Google Scholar 

  23. Akter S, Nanri A, Mizoue T, Noda M, Sawada N, Sasazuki S, et al. Dietary acid load and mortality among Japanese men and women: the Japan Public Health Center–based Prospective Study. Am J Clin Nutr. 2017;106(1):146–54.

    Article  PubMed  CAS  Google Scholar 

  24. Kucharska AM, Szostak-Węgierek DE, Waśkiewicz A, Piotrowski W, Stepaniak U, Pająk A, et al. Dietary acid load and cardiometabolic risk in the Polish adult population. Adv Clin Exp Med. 2018;27(10):1347–54.

    Article  PubMed  Google Scholar 

  25. Williams RS, Heilbronn LK, Chen DL, Coster AC, Greenfield JR, Samocha-Bonet D. Dietary acid load, metabolic acidosis and insulin resistance - Lessons from cross-sectional and overfeeding studies in humans. Clin Nutr (Edinb, Scotl). 2016;35(5):1084–90.

    Article  CAS  Google Scholar 

  26. Fagherazzi G, Vilier A, Bonnet F, Lajous M, Balkau B, Boutron-Ruault M-C, et al. Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study. Diabetologia. 2014;57(2):313–20.

    Article  PubMed  CAS  Google Scholar 

  27. Dehghan P, Abbasalizad-Farhangi M. Dietary acid load, blood pressure, fasting blood sugar and biomarkers of insulin resistance among adults: findings from an updated systematic review and meta-analysis. Int J Clin Pract. 2020;74(4):e13471.

    Article  PubMed  CAS  Google Scholar 

  28. Hadaegh F, Harati H, Ghanbarian A, Azizi F. Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study. Eur J Prevent Cardiol. 2006;13(4):571–7.

    Article  Google Scholar 

  29. Chen SW, Ji GY, Jiang Q, Wang P, Huang R, Ma WJ, et al. Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015–2017). BMC Public Health. 2019;19(1):1599.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Azizi F, Ghanbarian A, Momenan AA, Hadaegh F, Mirmiran P, Hedayati M, et al. Prevention of non-communicable disease in a population in nutrition transition: Tehran Lipid and Glucose Study phase II. Trials. 2009;10(1):1–15.

    Article  Google Scholar 

  31. Azizi F, Madjid M, Rahmani M, Emami H, Mirmiran P, Hadjipour R. Tehran Lipid and Glucose Study (TLGS): rationale and design. Iran J Endocrinol Metabol. 2000;2(2):77–86.

    Google Scholar 

  32. Momenan AA, Delshad M, Sarbazi N, Rezaei-Ghaleh N, Ghanbarian A, Azizi F. Reliability and validity of the Modifiable Activity Questionnaire (MAQ) in an Iranian urban adult population. Arch Iran Med. 2012;15(5):279–82.

    PubMed  Google Scholar 

  33. Asghari G, Rezazadeh A, Hosseini-Esfahani F, Mehrabi Y, Mirmiran P, Azizi F. Reliability, comparative validity and stability of dietary patterns derived from an FFQ in the Tehran Lipid and Glucose Study. Br J Nutr. 2012;108(6):1109–17.

    Article  PubMed  CAS  Google Scholar 

  34. M. Azar ES. Food Composition Table of Iran. National Nutrition and Food Research Institute, Tehran, Iran. 1980

  35. Scialla JJ, Appel LJ, Astor BC, Miller ER, Beddhu S, Woodward M, et al. Estimated net endogenous acid production and serum bicarbonate in African Americans with chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(7):1526–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Chen S-W, Ji G-Y, Jiang Q, Wang P, Huang R, Ma W-J, et al. Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015–2017). BMC Public Health. 2019;19(1):1599.

  37. Momenan AA, Delshad M, Sarbazi N, Rezaei GN, Ghanbarian A, Azizi F. Reliability and validity of the Modifiable Activity Questionnaire (MAQ) in an Iranian urban adult population. 2012.

  38. Hadaegh F, Harati H, Ghanbarian A, Azizi F. Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study. Eur J Cardiovasc Prevent Rehabil. 2006;13(4):571–7.

    Article  Google Scholar 

  39. Luepker RV, Apple FS, Christenson RH, Crow RS, Fortmann SP, Goff D, et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation. 2003;108(20):2543–9.

    Article  PubMed  Google Scholar 

  40. Khalili D, Azizi F, Asgari S, Zadeh-Vakili A, Momenan AA, Ghanbarian A, et al. Outcomes of a longitudinal population-based cohort study and pragmatic community trial: findings from 20 Years of the Tehran Lipid and Glucose Study. Int J Endocrinol Metab. 2018;16(4):e84748.

    PubMed  PubMed Central  Google Scholar 

  41. Abbasalizad-Farhangi M, Vajdi M, Najafi M. Dietary acid load significantly predicts 10-years survival in patients underwent coronary artery bypass grafting (CABG) surgery. PLoS ONE. 2019;14(10):e0223830.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Mazidi M, Mikhailidis DP, Banach M. Higher dietary acid load is associated with higher likelihood of peripheral arterial disease among American adults. J Diabetes Complic. 2018;32(6):565–9.

    Article  Google Scholar 

  43. Abbasalizad-Farhangi M, Nikniaz L, Nikniaz Z. Higher dietary acid load potentially increases serum triglyceride and obesity prevalence in adults: an updated systematic review and meta-analysis. PLoS ONE. 2019;14(5):e0216547.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Haghighatdoost F, Najafabadi MM, Bellissimo N, Azadbakht L. Association of dietary acid load with cardiovascular disease risk factors in patients with diabetic nephropathy. Nutrition. 2015;31(5):697–702.

    Article  PubMed  CAS  Google Scholar 

  45. Parohan M, Sadeghi A, Nasiri M, Maleki V, Khodadost M, Pirouzi A, et al. Dietary acid load and risk of hypertension: a systematic review and dose-response meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2019;29(7):665–75.

    Article  PubMed  CAS  Google Scholar 

  46. Krupp D, Esche J, Mensink GBM, Klenow S, Thamm M, Remer T. Dietary acid load and potassium intake associate with blood pressure and hypertension prevalence in a representative sample of the German adult population. Nutrients. 2018;10(1):103.

    Article  PubMed Central  CAS  Google Scholar 

  47. Osuna-Padilla I, Leal-Escobar G, Garza-García C, Rodríguez-Castellanos F. Carga ácida de la dieta; mecanismos y evidencia de sus repercusiones en la salud. Nefrologia. 2019;39(4):343–54.

    Article  PubMed  CAS  Google Scholar 

  48. Maurer M, Riesen W, Muser J, Hulter HN, Krapf R. Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol. 2003;284(1):F32-40.

    Article  PubMed  CAS  Google Scholar 

  49. Cappuccio FP, Kalaitzidis R, Duneclift S, Eastwood JB. Unravelling the links between calcium excretion, salt intake, hypertension, kidney stones and bone metabolism. J Nephrol. 2000;13(3):169–77.

    PubMed  CAS  Google Scholar 

  50. Dehghan P, Abbasalizad Farhangi M. Dietary acid load, blood pressure, fasting blood sugar and biomarkers of insulin resistance among adults: findings from an updated systematic review and meta-analysis. Int J Clin Pract. 2020;74(4):471.

    Article  CAS  Google Scholar 

  51. Luis D, Huang X, Riserus U, Sjögren P, Lindholm B, Arnlöv J, et al. Estimated dietary acid load is not associated with blood pressure or hypertension incidence in men who are approximately 70 years old. J Nutr. 2015;145(2):315–21.

    Article  PubMed  CAS  Google Scholar 

  52. Mohammadifard N, Karimi G, Khosravi A, Sarrafzadegan N, Jozan M, Zahed P, et al. High dietary acid load score is not associated with the risk of metabolic syndrome in Iranian adults. Int J Vitam Nutr Res. 2020.

  53. Yuzbashian E, Asghari G, Mirmiran P, Hosseini F-S, Azizi F. Associations of dietary macronutrients with glomerular filtration rate and kidney dysfunction: Tehran lipid and glucose study. Am J Nephrol. 2015;28(2):173–80.

    Article  CAS  Google Scholar 

  54. Ströhle A, Waldmann A, Koschizke J, Leitzmann C, Hahn A. Diet-dependent net endogenous acid load of vegan diets in relation to food groups and bone health-related nutrients: results from the German Vegan Study. Ann Nutri Metab. 2011;59(2–4):117–26.

    Article  CAS  Google Scholar 

  55. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med. 1997;336(16):1117–24.

    Article  PubMed  CAS  Google Scholar 

  56. Sebastian A, Sellmeyer DE, Stone KL, Cummings SR. Dietary ratio of animal to vegetable protein and rate of bone loss and risk of fracture in postmenopausal women. Am J Clin Nutr. 2001;74(3):411–2.

    Article  PubMed  CAS  Google Scholar 

  57. Adrogué HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med. 2007;356(19):1966–78.

    Article  PubMed  Google Scholar 

  58. van Haare J, Kooi ME, Vink H, Post MJ, van Teeffelen JW, Slenter J, et al. Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet. Cardiovasc Diabetol. 2015;14(1):150.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Axelsen LN, Calloe K, Braunstein TH, Riemann M, Hofgaard JP, Liang B, et al. Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis. Cardiovasc Diabetol. 2015;14(1):87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors would like to express their appreciation to the participants in the Tehran Lipid and Glucose Study for their cooperation, and the staff of the Research Institute for Endocrine Science, TLGS Unit.

Funding

This work was not supported by any funding agency.

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Authors and Affiliations

  1. Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran

    Parvin Mirmiran, Zeinab Houshialsadat, Zahra Bahadoran & Sajjad Khalili‑Moghadam

  2. Shohada Tajrish Medical Center, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran

    Mohammad Karim Shahrzad

  3. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fereidoun Azizi

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  1. Parvin Mirmiran
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  3. Zahra Bahadoran
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Contributions

PM designed the study. SK and ZB analyzed the data from the TLGS population, SK and ZH wrote the manuscript, ZH corrected the manuscript, FA and MS revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zahra Bahadoran or Mohammad Karim Shahrzad.

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The authors declare no competing interests.

Ethics Approval and consent to participate

Written informed consents were obtained from all participants at baseline. The study protocol complied with the 1975 Ethical Guidelines of the Helsinki Declaration and was approved by the Ethics Research Council of the Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences.

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Not Applicable.

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Mirmiran, P., Houshialsadat, Z., Bahadoran, Z. et al. Dietary acid load and risk of cardiovascular disease: a prospective population-based study. BMC Cardiovasc Disord 21, 432 (2021). https://doi.org/10.1186/s12872-021-02243-8

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Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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