Complementary Therapies in Medicine 71 (2022) 102887

Contents lists available at ScienceDirect

Complementary Therapies in Medicine

journal homepage: www.elsevier.com/locate/ctim

Dose-dependent effect of vinegar on blood pressure: A GRADE-assessed

systematic review and meta-analysis of randomized controlled trials
Hossein Shahinfar a, b, Mohammad Reza Amini c, Nastaran Payandeh d, Kimia Torabynasab a,
Sanaz Pourreza d, Shima Jazayeri a, *
a
Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
b
Student Research Committee, Faculty of Public Health, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran
c
Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food
Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran
d
Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Islamic Republic of Iran

A R T I C L E I N F O A B S T R A C T

Keywords: Background: There are controversial findings regarding the effect of vinegar on blood pressure based on the
Vinegar evidence accumulated so far.
Acetic acid Methods: A systematic search was conducted through PubMed, Scopus, and ISI Web of Science up to April 2022.
Blood pressure
We estimated the change in blood pressure for each 30 ml/d increments in vinegar consumption in each trial and
Hypertension
Systematic review
then, calculated the mean difference (MD) and 95 %CI using a fixed-effects model. A dose-response meta-analysis
Dose-response meta-analysis of differences in means provided us with the estimation of the dose-dependent effect. The certainty of evidence
was rated by the GRADE tool.
Results: Each 30 ml/d increment in vinegar consumption reduced SBP by − 3.25 mmHg (95 %CI: − 5.54, − 0.96;
I2 = 67.5 %, GRADE = low). Levels of SBP decreased linearly and slightly (Pnonlinearity = 0.69, Pdose-response =
0.02) up to vinegar consumption of 30 ml/d (MD30 ml/d: − 3.36, 95 %CI: − 5.77, − 0.94). Each 30 ml/
d increment in vinegar consumption reduced DBP by − 3.33 mmHg (95 %CI: − 4.16, − 2.49; I2 = 57.1 %,
GRADE = low). Levels of DBP decreased linearly and slightly (Pnonlinearity = 0.47, Pdose-response = 0.004) up to
vinegar consumption of 30 ml/d (MD30 ml/d: − 2.61, 95 %CI: − 4.15, − 1.06)
Conclusions: According to the findings, vinegar significantly reduces systolic and diastolic blood pressure and may
be considered an adjunct to hypertension treatment. Thus, clinicians could incorporate vinegar consumption as
part of their dietary advice for patients.

1. Introduction
High blood pressure is a leading cause of stroke and vital organ
failure. It also places a heavy burden on health care systems.1 The
prevalence of hypertension among adults 18 years and older was 45.4 %
in 2018, higher in men than in women. Also, it was declared that Hy­
pertension prevalence is also associated with aging.2 The assessment of
hypertensive patients should not be limited to blood pressure meaning
that potential organ damage and associated disease should be consid­
ered. This precise assessment might be more complicated in obese pa­
tients in comparison with patients in the normal weight range.3
Intensive lifestyle interventions play a substantial role in weight loss and
blood pressure decrement in obese hypertensive patients.4,5 Blood vessel
tone and structure are regulated by the endothelial function. Evidence
suggests that in conditions like hypertension, inflammation, and dia­
betes mellitus, the crucial function of the endothelium as a vasodilator is
impaired leading to ineffective vasodilation.4,6–9
In addition to anti-hypertensive drugs, dietary components such as
vinegar are promising for reducing hypertension.10 Vinegar has recently
attracted considerable attention because of its numerous health benefits,
such as anti-hyperglycemic, anti-hypercholesterolemia, anti­
hypertension, antimicrobial, antithrombotic, and anti-cancer effects.11
The mentioned beneficial effects led to growing interest in the advan­
tageous metabolic impacts of vinegar in recent decades. Vinegar con­
tains acetic acid and organic acids (formic acid, lactic acid, malic acid,
citric acid, saxonic acid, tartaric acid), amino acids, peptides, vitamins,

* Corresponding author.
E-mail address: jazayeri.sh@iums.ac.ir (S. Jazayeri).

https://doi.org/10.1016/j.ctim.2022.102887
Received 8 May 2022; Received in revised form 6 August 2022; Accepted 20 September 2022
Available online 21 September 2022
0965-2299/© 2022 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
H. Shahinfar et al.
and mineral salts (catechins, caffeic acid, ferulic acid.12–15 Various kinds
of vinegar, depending on their sources, with unique properties, have
been studied.12,16–19 Apple cider vinegar is a type of vinegar rich in
flavonoids, including gallic acid, catechins, caffeic acid, and ferulic acid.
Studies have demonstrated that apple cider vinegar has insurmountable
impacts on those with type 2 diabetes.20 Additionally, studies on a
pomegranate-based vinegar revealed that it has the potency to increase
gene expression related to fatty acid oxidation.18 Bouazza also found
that kinds of vinegar play a substantial role in lipid metabolism and liver
protection in rats with high-fat diets.21
The effects of vinegar on inflammation and hypertension have been
studied separately so far.15,17,19,20 Therefore, our goal was to investigate
whether vinegar could lower blood pressure in adults struggling with
hypertension through systematic review and meta-analysis. Having
found no cohort studies investigating vinegar’s impact on blood pres­
sure, we restricted this study to RCTs.
2. Methods
We followed the Preferred Reporting Items for Systematic Reviews
and Meta-analysis (PRISMA-2020) guidelines to present this systematic
review and meta-analysis22 (Supplementary Table 1). The protocol of
this systematic review was registered at Open Science Framework
(https://osf.io/uz84f, registered form: https://osf.io/tvwcf/, registra­
tion https://doi.org/10.17605/OSF.IO/UZ84F). The PICOS model23
included questions about participants (adults aged > 18 years), inter­
vention (vinegar) comparator (placebo or matched intervention),
outcome (SBP and DBP) and study design (parallel and cross-over ran­
domized clinical trial) were accomplished.
2.1. Search strategy
Two independent authors (H.SH., MR.A.) conducted a literature
search and study selection. An independent third investigator (SJ)
finalized the inclusion of articles. A systematic search was carried out
through PubMed/Medline, Scopus, ISI Web of Science, Embase, and
Google Scholar up to April 2022. We applied relevant search terms to
find published English studies (Supplementary Table 2). The between-
reviewer agreement at the full-text screening stage was assessed and
reported as Cohen’s kappa coefficient (κ)24 (Supplementary Table 3).
The interpretation of Cohen’s kappa coefficient was illustrated in Sup­
plementary Table 4. Additionally, we manually checked the references
of the included articles in order to avoid missing any related studies.
2.2. Eligibility criteria
Inclusion criteria for potentially relevant studies were as follows: (a)
randomized clinical trials (RCTs) with either parallel or cross-over de­
signs; (b) participants aged 18 or older; (c) examining SBPs and DBPs
after vinegar administration; and (d) reporting outcomes at baseline and
at trial end (or reported changes in outcomes) for each group (vinegar
and placebo). Considering studies with the same population, we
included those with complete findings. Letters, comments, conference
papers, reviews, meta-analyses, and ecologic studies were all excluded,
as they were conducted on animals, pregnant women, and children, or
they did not assess vinegar’s effects in combination with other in­
terventions. Unpublished and grey literature like patents, congress ab­
stracts, and dissertations were excluded, as well.
2.3. Data extraction
During study selection and data extraction, two independent re­
searchers were involved (H.SH. and MR. A third reviewer was consulted
when there was a disagreement about eligibility (SJ). The following data
were collected from each study: study characteristics (first author’s
name, year of publication, study location, publishing year, and study
2
Complementary Therapies in Medicine 71 (2022) 102887
design), participant characteristics (mean age and gender of participants
separately by intervention and non-intervention groups, health status of
population, number of participants in each group) and intervention
(type, dose and duration) and mean and SD of obesity indices at base­
line, and end of study or changes between baseline and post-
intervention.
2.4. Quality assessment of studies
Based on the Revised Cochrane risk-of-bias tool for randomized trials
(RoB 2), the quality of studies was assessed for bias.25 Several meth­
odological aspects were considered, including random sequence gener­
ation, allocation concealment, blinding of participants and personnel,
blinding of outcome assessments, incomplete outcome data, selective
reporting, and other potential threats to validity. The Cochrane Hand­
book recommends stratifying studies based on low, high, or fair risk of
bias. Each trial was given an overall quality score based on its risk of bias
domain: good (≤ 1/5 items were unknown and none were high), fair (≤
2/5 items were unclear or at least one high), and high (≥ 2/5 items were
high). Discussions were held to resolve disagreements regarding the risk
of bias assessment.
2.5. Quantitative data synthesis and statistical analysis
Based on mean and standard deviation (SD) values of the baseline
and the end of the research in both intervention and control groups, we
estimated vinegar’s effect on blood pressure, including SBP and DBP.
When the studies did not provide mean and SD, we converted the
available statistical data into mean and SD using the appropriate for­
mula: SD difference = square root [(SD pre-treatment)2 + (SD post-treatment)2 −
(2 × R × SD pre-treatment × SD post-treatment)], assuming a correlation co­
efficient (R) 0.9 as it is a conservative estimate for an expected range of
0–1.26 When means (± SD) of outcome measures was not directly
available and a standard error of the mean (SEM) was presented in place
of SD, we converted it to SD using this formula: SD = SEM × √n, being
“n” the number of subjects in each group. If medians and inter-quartile
range were reported, mean and SD values were estimated using SD =
IQR/1.35 (symmetrical data distribution).27 Ultimately, we were able to
extract graphically reported data using GetData Graph Digitizer version
2.24.28
Initially, a fixed-effects model was used to determine the relationship
with forest plots. The degree of heterogeneity was defined based on the
I-squared statistic, and it was considered substantially significant when
Cochrane’s test showed I2 greater than 50 % with a p-value < 0.1.29 To
detect potential heterogeneity, a subgroup analysis was performed
based on health status, dose, duration, number of studies, and mean age.
Hartung-Knapp adjustment was applied since the number of included
studies for each factor was small.30 This model provides a more robust
estimate of variance and broader CIs. Influence analysis enabled us to
estimate the possible effect of each randomized clinical trial on pooled
effect size. Publication bias assessment was performed by inspection of
funnel plot asymmetry test,31 and Egger’s regression test.32 Second, we
used the method introduced by Crippa and Orsini33 to calculate the
mean difference (MD) and its corresponding SD of change in SBP and
DBP for every 30 ml/d increments in vinegar consumption in the
intervention group relative to the control group in each trial. This
method required the dose (ml/d) of vinegar consumed, the mean, and its
corresponding SD of change in SBP and DBP, and the number of par­
ticipants in each study arm. For comparisons including ≤ 5 studies,
trial-specific results were pooled using a fixed-effects model.34
Following that, we applied a series of pre-defined subgroup analyses
based on health status, follow-up duration, dose, and sample size. We
used I2 statistic and χ2 test for quantitative assessment of heterogeneity
and homogeneity evaluation, respectively.35 Finally, A dose-response
meta-analysis provided further insight into the shape of the effect of
vinegar on SBP and DBP.34 Statistical analyses were conducted using
H. Shahinfar et al. Complementary Therapies in Medicine 71 (2022) 102887

STATA software version 16.1. A two-tailed P value of less than 0.05 was
considered significant.
2.6. Grading the evidence
Using the GRADE approach, Pairs of authors (HSH and NP) inde­
pendently assessed the certainty of the evidence.36 Downgrading evi­
dence is based on limitations, inconsistencies, indirectness, imprecision,
and publication bias. There are several criteria used to upgrade the
quality of the evidence including a large magnitude of association, a
dose-response gradient, and attenuation by plausible confounding.
Disagreements were solved by consensus. Based on the mentioned
criteria, the certainty of each evidence was rated as high, moderate, low,
and very low. Minimal clinically important difference (MCID) for SBP
and DBP was defined as 2 mmHg.37
3. Results
3.1. Search results
The study selection process is summarized in Supplementary Fig. 1.
Initially, 362 potentially relevant studies were found, of which 230 were
duplicates. Based on title and abstract screening, 19 records were
considered for full-text revision. The between-reviewer agreement for
including studies was near perfect (Cohen’s kappa = 0.84) at the title-
abstract screening step. Of these, we additionally excluded 15 studies
for the following reasons: did not provide adequate data (n = 4), did not
report relevant outcome (n = 8), as well as records that were review
articles (n = 3). Eventually, a total of 4 RCTs were included for the
current systematic review and meta-analysis. All the 4 studies had re­
ported data on BP.20,38,39 The between-reviewer agreement for
including studies was near perfect (Cohen’s kappa = 0.82) at the
full-text screening step.
3.2. Study characteristics
In Table 1, the general characteristics and main outcomes of the
included RCTs are summarized. Included studies were published from
2009 to 2019 with a total of 298 individuals, using parallel design.20,38,
39
Intervention periods ranged from 7 to 12 weeks, and the dose of
vinegar varied from 15 ml to 30 ml daily. Studies were conducted in
Pakistan,39 Iran,20 and Japan.38
The participants in the mentioned studies, aged 44–51 years, had
some health issues such as overweight and obesity,38,39
hyperlipidemia,39 and T2DM with dyslipidemia.20 All the records
examined the effect of vinegar on both genders. Using RoB 2, the
Revised Cochrane risk-of-bias tool for randomized trials, the risk of bias
in two studies was graded low,39,40 while two others were graded fair
(Supplementary Table 5).20,38
3.3. The effect of vinegar on systolic blood pressure
The fixed-effect model demonstrated that the pooled mean effect size
had a significant reduction (WMD: − 3.82 mmHg, 95 % CI: − 4.69, −
2.94, p < 0.001) with considerable heterogeneity (I2 = 74.6 %; p =
0.003) (Supplementary Fig. 2). After the Hartung-Knapp adjustment due
to the small number of the included studies in the analysis, the results
changed (MD: − 2.81 mmHg; 95 % CI: − 7.09 to 1.46; p = 0.14). In these
analyzes, However, subgroup analysis showed that patients with
hyperlipidemia, age greater than 45 years old, dose less than 30 ml/day,
duration less than 10 weeks, sample size less than 70 subjects and
intervention type were potential sources of heterogeneity (Table 2).
Each 30 ml/d increment in vinegar consumption reduced SBP by −
3.25 mmHg (95 %CI: − 5.54, − 0.96; I2 = 67.5 %, Fig. 1). The effect size
remained significant after the step-wise exclusion of each study from the
main analysis (MD range: − 4.62 to − 2.03). Visual inspection of the
funnel plot (Supplementary Fig. 3) and Egger’s test (P = 0.18) revealed
evidence of publication bias among included studies.
Dose-dependent effects of vinegar on levels of SBP are indicated in
Fig. 2 and Table 3. Levels of SBP decreased linearly and slightly (Pnon­
linearity = 0.69, Pdose-response = 0.02) up to vinegar consumption of 30 ml/
d (MD30 ml/d: − 3.36, 95 %CI: − 5.77, − 0.94).
3.4. The effect of vinegar on diastolic blood pressure
This meta-analysis illustrated that pooled effect size had consider­
ably declined in DBP (WMD: − 3.01 mmHg; 95 % CI, − 3.80 to − 2.22,
p < 0.001) with significant heterogeneity (I2 = 73.3 %, p = 0.01)
(Supplementary Fig. 4). Applying subgroup analysis, we found that a
dose of 30 ml/day, greater or equal, was the potential source of het­
erogeneity. (Table 2). In addition, significant change was found after
performing the Hartung-Knapp adjustment (MD: − 2.43 mmHg; 95 %
CI: − 8.21 to 3.34; p = 0.27).
Each 30 ml/d increment in vinegar consumption reduced DBP by
− 3.33 mmHg (95 %CI: − 4.16, − 2.49; I2 = 57.1 %, Fig. 3). The effect
size remained significant after the step-wise exclusion of each study
from the main analysis (MD range: − 3.45 to − 1.16). Visual inspection
of the funnel plot (Supplementary Fig. 5) and Egger’s test (P = 0.06)

Table 1
Demographic characteristics of the included studies.
First Location Study Design Health status Gender Sample Duration Mean Baseline Intervention Outcome
author size (week) age BMI (kg/
Treatment Control
(year) (year) m2)
group group

Kondo Japan Randomized, Obese Both 101 12 44.1 27.2 30 ml Placebo SBP/
et al. double-blind, vinegar DBP
(2009) placebo-controlled,
parallel trial
Ali et al. Pakistan Randomized, single- T2DM Both 85 10 42.6 27 15 ml/30 ml Placebo SBP/
(2018) blind, placebo- vinegar DBP
controlled, parallel
trial
Ali et al. Pakistan Randomized, Hyperlipidemic Both 50 7 49.0 26.7 30 ml Placebo SBP/
(2018) double-blind, vinegar DBP
placebo-controlled,
parallel trial
Gheflati Iran Randomized, T2DM and Both 62 8 50.7 28.9 20 ml No SBP/
et al. placebo-controlled, dyslipidemia vinegar intervention DBP
(2019) parallel trial

Abbreviations: T2DM, Type 2 Diabetes Mellitus; SBP, Systolic Blood Pressure; DBP, Diastolic Blood Pressure; BMI, Body Mass Index; MetS; Metabolic Syndrome; mg,
milligram.

3
H. Shahinfar et al. Complementary Therapies in Medicine 71 (2022) 102887

Table 2
Subgroup analysis of included randomized controlled trials in meta-analysis of the effect of vinegar on blood pressure.
Group No. of trials WMD (95 % CI) P value I2 (%) P-heterogeneity P for between subgroup heterogeneity

SBP
Health status < 0.001
Obese 3 -4.49 (− 5.39, − 3.50) < 0.001 25.2 0.26
Hyperlipidemic 2 -0.13 (− 2.23, 2.49) 0.91 0 0.43
Age < 0.001
≤ 45 3 -4.49 (− 5.39, − 3.50) < 0.001 25.2 0.26
> 45 2 -0.13 (− 2.23, 2.49) 0.91 0 0.43
Dose 0.09
< 30 2 -1.34 (− 4.38, 1.70) 0.38 19.0 0.26
≥ 30 3 -4.04 (− 4.95, − 3.12) < 0.001 83.0 0.003
Duration < 0.001
< 10 2 0.13 (− 2.23, 2.49) 0.91 0 0.43
≥ 10 3 -4.44 (− 5.39, − 3.50) < 0.001 25.2 0.26
Sample size < 0.001
< 70 2 0.10 (− 0.26, 0.70) 0.58 0 0.54
> 70 3 -0.73 (− 0.97, − 0.48) < 0.001 90.5 < 0.001
Intervention type
Dates vinegar 2 -3.99 (− 4.94, − 3.04) < 0.001 91.4 0.001 0.35
Apple cider vinegar 3 -2.85 (− 5.08, − 0.61) 0.01 38.8 0.19
DBP
Dose 0.01
< 30 2 -0.62 (− 2.61, 1.35) 0.53 75.5 0.04
≥ 30 2 -3.46 (− 4.33, − 2.60) < 0.001 0 0.47

Abbreviations: N: number; CI, confidence interval; WMD: weighted mean differences.

Fig. 1. linear dose-response relations between vinegar and unstandardized mean difference in systolic blood pressure. The 95 % CI is revealed in the shaded regions.

indicated evidence of publication bias among included studies.
Dose-dependent effects of vinegar on levels of DBP are indicated in
Fig. 4 and Table 3. Levels of DBP decreased linearly and slightly (Pnon­
linearity = 0.47, Pdose-response = 0.004) up to vinegar consumption of
30 ml/d (MD30 ml/d: − 2.61, 95 %CI: − 4.15, − 1.06).
3.5. Grading the evidence
Rating certainty of the evidence, we applied the GRADE tool. Serious
inconsistency, indirectness, and imprecision downgraded certainty of
the evidence, while the dose-response gradient upgraded it. Finally,
both outcomes rated low (Supplementary Table 6).
4. Discussion
Based on our systematic review and meta-analysis results, we can
suggest that vinegar consumption might yield insurmountable impacts
on both SBP and DBP. Our findings from non-linear analysis also
revealed a consequential lowering effect of vinegar on SBP and DBP
levels in doses of 30 ml/day. Regarding health concerns of hypertension,
it is associated with heart, brain, and kidney issues.1 While there are
several constructive approaches to manage hypertension, lifestyle
modification is the first line of treatment in these cases.41
Although experimental studies have suggested several potential
mechanisms, the mechanism by which vinegar influences hypertension
is not well understood. Vinegar’s main component, acetic acid (AcOH),
could have a role in these mechanisms.12 Kondo et al. Claimed that
vinegar acetic acid might reduce blood pressure by improving calcium
absorption, and its effect on the renin-angiotensin system.42 In this way,
acetic acid in vinegar curtails the activity of renin and inhibits the
angiotensin-converting enzyme activity.42–44 Higher calcium concen­
tration in vascular smooth muscle cells, resulting from improved cal­
cium absorption, can affect blood pressure.45 Thus, it regulates blood
pressure through the renin-angiotensin-aldosterone system (RAAS) with

4
H. Shahinfar et al. Complementary Therapies in Medicine 71 (2022) 102887

Fig. 2. Non-linear dose-response relations between vinegar and unstandardized
mean difference in systolic blood pressure. The 95 % CI is revealed in the
shaded regions.
vasoconstriction and increased vascular volume.45,46 They also
described how to increase blood pressure by lowering calcium concen­
tration through these three mechanisms: (1) parathyroid function, (2)
vitamin D, and (3) the renin-angiotensin-aldosterone system (RAAS).46
In this regard, animal studies have also suggested that acetic acid may
dwindle serum renin activity, concentrations of angiotensin-converting
enzyme (ACE), angiotensin II, and aldosterone in hypertensive rats.47
Another investigation on rats with hypertension, conducted by Kondo
et al., revealed that the presence of vinegar in the diet leads to advan­
tageous effects on lowering blood pressure.42 The results of animal
studies have shown that consuming 1.6 % vinegar for 32 days could
compensate for a low-calcium diet since it leads to a remarkable rise in
calcium absorption.48 Consequently, it is conceivable to illustrate that
vinegar beneficially affects systolic and diastolic blood pressure by
improving calcium absorption.48 On the other hand, Vinegar poly­
phenols highly promote endothelial function through anti-inflammatory
and antioxidative effects. They also stimulate nitric oxide (NO)
production.49
In line with our result, a study by Tanaka et al. indicated that vinegar
and dried bonito with or without GABA would possibly affect BP in
mildly or moderately hypertensive patients.50 Lexin et al. also showed
that the combination of vinegar and nifedipine reduced blood pressure
efficaciously compared to vinegar or nifedipine alone.47 There is some
evidence contrasting our results. An investigation conducted by Ali et al.
in 2018 demonstrated that consumption of 500 ml of dates vinegar
along with garlic juice for 10 weeks had no considerable effect on in­
dividuals’ blood pressure.43 Furthermore, weight gain has been linked to
increased blood pressure in several studies.51,52 Obesity increases the
risk of hypertension by 3.5 times, and adipose tissue accounts for 60 %
of the disease.53 Additionally, obese people have a remarkably subor­
dinate acetic acid turnover compared with healthy people, which may
provide some explanation for the variable effects of dietary acetic acid
supplementation.8,51 According to studies, vinegar consumption pro­
motes the feeling of satiety in people. Although this should have resulted
in body weight regulation, no statistically significant anthropometric
improvement was seen among overweight or obese participants.8
Increased dietary acetic acid has been shown to improve metabolic
outcomes in rodents in preclinical studies.54–56 A meta-analysis by
Valdes et al. also showed that individuals with type 2 diabetes or obesity
might benefit from supplementing their diet with dietary acetic acid,
which has no adverse side effects and reduces plasma triacylglycerol and

Table 3
The effects of different doses of vinegar on blood pressure form the nonlinear dose-response meta-analysis (mean difference and 95 % confidence interval).
Vinegar 0 (Ref) 10 20 30 40 50 60 70 80 90 100
intake (ml/
d)

SBP 0 0.72 -1.25 -3.36 -5.47 -7.58 -9.69 -11.8 -13.9 -16.0 -18.1
(mmHg) (− 8.24, (− 6.10, (− 5.77, (− 11.8, (− 18.8, (− 26.0, (− 33.2, (− 40.4, (− 47.6, (− 54.8,
9.68) 3.61) − 0.94) 0.90) 3.72) 6.66) 9.63) 12.6) 15.6) 18.6)
DBP 0 2.76 0.22 -2.61 -5.43 -8.26 -11.0 -13.9 -16.7 -19.5 -22.3
(mmHg) (− 7.18, (− 5.14, (− 4.15, (− 11.4, (− 19.6, (− 27.9, (− 36.2, (− 44.5, (− 52.8, (− 61.1,
12.7) 5.58) − 1.06) 0.59) 3.16) 5.79) 8.44) 11.0) 13.7) 16.4)

Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.

Fig. 3. Linear dose-response relations between vinegar and unstandardized mean difference in diastolic blood pressure. The 95 % CI is revealed in the
shaded regions.

5
H. Shahinfar et al.
Fig. 4. Non-linear dose-response relations between vinegar and unstandardized
mean difference in diastolic blood pressure. The 95 % CI is revealed in the
shaded regions.
54
fasting blood glucose levels. However, they found no significant effects
on HbA1c, HDL, or anthropometric markers.54 Various interventions,
different study durations, undeniable confounders in each study, and
lack of adequate biochemical data may account for the discrepancies
observed in the results. using subgroup analysis, we also found that some
factors such as sample size might affect the results. It is of paramount
importance to consider the daily dose of vinegar consumed. Every 30 ml
increase in vinegar consumption can decrease − 3.33 and − 3.25 mm of
mercury in diastolic and systolic blood pressure, respectively.
Consuming vinegar fewer than 30 ml per day and for less than ten
weeks, the presence of hyperlipidemia, and age older than 45 years
might confound the outcomes. Triglycerides and cholesterol, accumu­
lating in blood vessels, might disturb blood flow, thus causing Hyper­
tension.57 Systolic and diastolic blood pressure increase as a result of
physiological changes associated with aging.58,59 These age-related
physiological alterations are most likely due to changes in arterial.60,
61
For accurate results, additional investigations are required.
To the authors knowledge, our meta-analysis displays the first
investigation into the effects of vinegar on blood pressure which could
be considered as a major strength. The present meta-analysis provided
novel insights into the dose-dependent effect of vinegar on blood pres­
sure in adults that were not presented in the previous published meta-
analyses. We evaluated the certainty of evidence using the GRADE
approach, used MCID thresholds.37 Moreover, we performed systematic
literature research precisely, and data were cross-checked indepen­
dently by authors. Our search methodology included several databases.
Since our study only included RCTs, the causal inference obtained from
our study is strong. Also, subgroup analysis was performed to determine
the effects and detect possible sources of heterogeneity, although the
heterogeneity between studies was reduced by conducting subgroup
analysis.
However, there are some potential limitations needed to be consid­
ered in future studies: our main limitation is that, due to inadequate
information, we had insufficient evidence for blood pressure lowering
medications and other cardiovascular risk factors. Considering the
relatively low number of trials included in the subgroup analysis, more
studies are needed to confirm the findings. Furthermore, there was a
high level of heterogeneity, limiting the generalizability of the findings.
A few eligible RCTs were included in this meta-analysis. In addition, due
to the short duration of intervention in included studies (7–12 weeks),
there is a limitation for understanding the long-term effects. Further
research with a large population and a long period of intervention is
needed to evaluate the safety and efficacy of vinegar on improving blood
pressure. Most of the studies considered showed some form of bias, and
thus it is hard to reach a definitive conclusion. The certainty of the
6
Complementary Therapies in Medicine 71 (2022) 102887
evidence was low for both SBP and DBP. Given the limitations, the
findings of the present meta-analysis should be interpreted with caution.
5. Conclusion
In summary, we found that consuming vinegar at a dose of 30 ml/
d may reduce both SBP and DBP; However, a well-designed RCT with a
sufficient sample size and extended intervention period is required to
assess the effects of vinegar on blood pressure accurately. Through these
investigations, the effect of vinegar on healthy individuals, patients with
metabolic syndrome, impaired glucose tolerance, and hypertension
might be precisely explained. Hypertensive patients might take advan­
tage of our investigation as well since clinicians could recommend
vinegar consumption as part of their diet. In a clinical setting, this
approach will improve the effectiveness of high blood pressure control,
facilitate the development of an effective hypertension self-management
program, and mitigate the complications associated with poorly
controlled hypertension.
CRediT authorship contribution statement
HSH and MRA designed the study. HSH and MRA did the literature
search and screening data. HSH, NP and SP performed data extraction
and quality assessment, independently. HSH and KT analyzed and
interpreted data and wrote the manuscript. SJ supervised the study. All
authors read and approved the final manuscript.
Funding source
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
The authors declared no conflicts of interest.
Availability of data and materials
The datasets generated or analyzed during the current study are not
publicly available but are available from the corresponding author on
reasonable request.
Acknowledgments
This is a part of the Ph.D. seminar course of Hossein Shahinfar. The
authors thank the Iran University of Medical Sciences (IUMS).
Appendix A. Supporting information
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.ctim.2022.102887.
References
1. Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and
effective interventions for elevated blood pressure and hypertension. Nat Rev
Cardiol. 2021;2021. https://doi.org/10.1038/s41569-021-00559-8.
2. Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. Hypertension prevalence among
adults aged 18 and over: United States, 2017–2018. NCHS Data Brief. 2020;(364):
1–8.
3. Narkiewicz K. Diagnosis and management of hypertension in obesity. Obes Rev.
2006;7(2):155–162. https://doi.org/10.1111/j.1467-789X.2006.00226.x.
4. Doroszko A, Janus A, Szahidewicz-Krupska E, Mazur G, Derkacz A. Resistant
hypertension. Adv Clin Exp Med. 2016;25(1):173–183. https://doi.org/10.17219/
acem/58998.
5. Yazdanpanah Y, Saleh Moghadam AR, Mazlom SR, Haji Ali Beigloo R, Mohajer S.
Effect of an educational program based on health belief model on medication
adherence in elderly patients with hypertension. Evid Based Care. 2019;9(1):52–62.
https://doi.org/10.22038/ebcj.2019.35215.1895.
H. Shahinfar et al.
6. Mikolajczyk TP, Guzik TJ. Adaptive immunity in hypertension. Curr Hypertens Rep.
2019;21(9):68. https://doi.org/10.1007/s11906-019-0971-6.
7. Ferrari R, Aguiar C, Alegria E, et al. Current practice in identifying and treating
cardiovascular risk, with a focus on residual risk associated with atherogenic
dyslipidaemia. Eur Heart J Suppl. 2016;18(Suppl. C):SC2–Sc12. https://doi.org/
10.1093/eurheartj/suw009.
8. Shishehbor F, Mansoori A, Shirani F. Vinegar consumption can attenuate
postprandial glucose and insulin responses; a systematic review and meta-analysis of
clinical trials. Diabetes Res Clin Pract. 2017;127:1–9. https://doi.org/10.1016/j.
diabres.2017.01.021.
9. Goswami B. Serum levels of nitric oxide and its correlation with endothelial nitric
oxide synthase gene expression among type 2 diabetic patients with or without
hypertension: a comparative study in a tertiary care hospital of North East India;
2021;
10. Ahmad L. Anti-hypertensive plants of rural Pakistan: current use and future
potential; 2018.
11. Beh BK, Mohamad NE, Yeap SK, et al. Anti-obesity and anti-inflammatory effects of
synthetic acetic acid vinegar and Nipa vinegar on high-fat-diet-induced obese mice.
Sci Rep. 2017;7(1). https://doi.org/10.1038/s41598-017-06235-7 [6664-6664].
12. Mahmoodi M, Hosseini-zijoud S-M, Nabati S, et al. The effect of white vinegar on
some blood biochemical factors in type 2 diabetic patients. J Diabetes Endocrinol.
2013;4(1):1–5.
13. Cocchi M, Durante C, Grandi M, Lambertini P, Manzini D, Marchetti A.
Simultaneous determination of sugars and organic acids in aged vinegars and
chemometric data analysis. Talanta. 2006;69(5):1166–1175. https://doi.org/
10.1016/j.talanta.2005.12.032.
14. Morales ML, Tesfaye W, García-Parrilla MC, Casas JA, Troncoso AM. Evolution of
the aroma profile of sherry wine vinegars during an experimental aging in wood.
J Agric Food Chem. 2002;50(11):3173–3178. https://doi.org/10.1021/jf011313w.
15. Petsiou EI, Mitrou PI, Raptis SA, Dimitriadis GD. Effect and mechanisms of action of
vinegar on glucose metabolism, lipid profile, and body weight. Nutr Rev. 2014;72
(10):651–661. https://doi.org/10.1111/nure.12125.
16. Nazni P, Singh R, Devi RS, et al. Assessment of hypoglycemic effects of apple cider
vinegar in type 2 diabetes. Int J Food Nutr Sci. 2015;4(1):206.
17. Budak NH, Aykin E, Seydim AC, Greene AK, Guzel-Seydim ZB. Functional properties
of vinegar. J Food Sci. 2014;79(5):R757–R764. https://doi.org/10.1111/1750-
3841.12434.
18. Ok E, Do G-M, Lim Y, Park J-E, Park Y-J, Kwon O. Pomegranate vinegar attenuates
adiposity in obese rats through coordinated control of AMPK signaling in the liver
and adipose tissue. Lipids Health Dis. 2013;12. https://doi.org/10.1186/1476-511X-
12-163 [163-163].
19. Shen F, Feng J, Wang X, et al. Vinegar treatment prevents the development of
murine experimental colitis via inhibition of inflammation and apoptosis. J Agric
Food Chem. 2016;64(5):1111–1121. https://doi.org/10.1021/acs.jafc.5b05415.
20. Gheflati A, Bashiri R, Ghadiri-Anari A, Reza JZ, Kord MT, Nadjarzadeh A. The effect
of apple vinegar consumption on glycemic indices, blood pressure, oxidative stress,
and homocysteine in patients with type 2 diabetes and dyslipidemia: a randomized
controlled clinical trial. Clin Nutr ESPEN. 2019;33:132–138. https://doi.org/
10.1016/j.clnesp.2019.06.006.
21. Bouazza A, Bitam A, Amiali M, Bounihi A, Yargui L, Koceir EA. Effect of fruit
vinegars on liver damage and oxidative stress in high-fat-fed rats. Pharmaceut Biol.
2016;54(2):260–265. https://doi.org/10.3109/13880209.2015.1031910.
22. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated
guideline for reporting systematic reviews. Bmj. 2021;372(n71). https://doi.org/
10.1136/bmj.n71.
23. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical
question: a key to evidence-based decisions. ACP J Club. 1995;123(3):A12–A13.
24. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20
(1):37–46.
25. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for
assessing risk of bias in randomised trials. Bmj. 2011;343:d5928. https://doi.org/
10.1136/bmj.d5928.
26. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Introduction to Meta-analysis.
John Wiley & Sons; 2011.
27. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median,
range, and the size of a sample. BMC Med Res Methodol. 20 2005;5:13. https://doi.
org/10.1186/1471-2288-5-13.
28. Fedorov S. GetData Graph Digitizer version 2.24; 2002. Available at 〈www.getdata-
graph-digitizer.com〉, 541:542.
29. Cochran WG. The combination of estimates from different experiments. Biometrics.
1954;10(1):101–129.
30. IntHout J, Ioannidis JP, Borm GF. The Hartung-Knapp-Sidik-Jonkman method for
random effects meta-analysis is straightforward and considerably outperforms the
standard DerSimonian-Laird method. BMC Med Res Methodol. 2014;14:25. https://
doi.org/10.1186/1471-2288-14-25.
31. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour-enhanced meta-
analysis funnel plots help distinguish publication bias from other causes of
asymmetry. J Clin Epidemiol. 2008;61(10):991–996. https://doi.org/10.1016/j.
jclinepi.2007.11.010.
32. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a
simple, graphical test. Bmj. 1997;315(7109):629–634. https://doi.org/10.1136/
bmj.315.7109.629.
33. Crippa A, Orsini N. Dose-response meta-analysis of differences in means. BMC Med
Res Methodol. 2016;16:91. https://doi.org/10.1186/s12874-016-0189-0.
34. Crippa A, Orsini N. Dose-response meta-analysis of differences in means. BMC Med
Res Methodol. 2016;16(1):1–10.
7
Complementary Therapies in Medicine 71 (2022) 102887
35. Higgins J, Savović J, Page MJ, Elbers RG, Sterne J. Assessing risk of bias in a
randomized trial. Cochrane Handb Syst Rev Interv. 2019;6:205–228.
36. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE
evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):
383–394. https://doi.org/10.1016/j.jclinepi.2010.04.026.
37. Ge L, Sadeghirad B, Ball GDC, et al. Comparison of dietary macronutrient patterns of
14 popular named dietary programmes for weight and cardiovascular risk factor
reduction in adults: systematic review and network meta-analysis of randomised
trials. Bmj. 2020;369(m696). https://doi.org/10.1136/bmj.m696.
38. Kondo T, Kishi M, Fushimi T, Ugajin S, Kaga T. Vinegar intake reduces body weight,
body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci
Biotechnol Biochem. 2009;73(8):1837–1843. https://doi.org/10.1271/bbb.90231.
39. Ali Z, Ma H, Rashid MT, Ayim I, Wali A. Reduction of body weight, body fat mass,
and serum leptin levels by addition of new beverage in normal diet of obese subjects.
J Food Biochem. 2018;42(5), e12554.
40. Ali Z, Ma H, Ayim I, Wali A. Efficacy of new beverage made of dates vinegar and
garlic juice in improving serum lipid profile parameters and inflammatory
biomarkers of mildly hyperlipidemic adults: a double-blinded, randomized, placebo-
controlled study. J Food Biochem. 2018;42(5), e12545.
41. Seedat YK. Nutritional aspects of hypertension. S Afr Med J. 1989;75(4):175–177.
42. Kondo S, Tayama K, Tsukamoto Y, Ikeda K, Yamori Y. Antihypertensive effects of
acetic acid and vinegar on spontaneously hypertensive rats. Biosci Biotechnol
Biochem. 2001;65(12):2690–2694. https://doi.org/10.1271/bbb.65.2690.
43. Ali Z, Ma H, Wali A, Ayim I, Sharif MN. Daily date vinegar consumption improves
hyperlipidemia, β-carotenoid and inflammatory biomarkers in mildly
hypercholesterolemic adults. /09/01/ 2019;17-18:100265 J Herb Med. 2019.
https://doi.org/10.1016/j.hermed.2019.100265.
44. Honsho S, Sugiyama A, Takahara A, Satoh Y, Nakamura Y, Hashimoto K. A red wine
vinegar beverage can inhibit the renin-angiotensin system: experimental evidence in
vivo. Biol Pharm Bull. 2005;28(7):1208–1210. https://doi.org/10.1248/
bpb.28.1208.
45. Simonetti G, Mohaupt M. Calcium and blood pressure. Ther Umsch. 2007;64(5):
249–252. https://doi.org/10.1024/0040-5930.64.5.249 [Kalzium und Blutdruck].
46. Villa-Etchegoyen C, Lombarte M, Matamoros N, Belizán JM, Cormick G.
Mechanisms involved in the relationship between low calcium intake and high blood
pressure. Nutrients. 2019;11(5):1112. https://doi.org/10.3390/nu11051112.
47. Na L, Chu X, Jiang S, et al. Vinegar decreases blood pressure by down-regulating
AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously
hypertensive rats. Eur J Nutr. 2016;55(3):1245–1253. https://doi.org/10.1007/
s00394-015-0937-7.
48. Kishi M, Fukaya M, Tsukamoto Y, Nagasawa T, Takehana K, Nishizawa N.
Enhancing effect of dietary vinegar on the intestinal absorption of calcium in
ovariectomized rats. Biosci Biotechnol Biochem. 1999;63(5):905–910. https://doi.
org/10.1271/bbb.63.905.
49. de Brito Alves JL, de Sousa VP, Cavalcanti Neto MP, et al. New insights on the use of
dietary polyphenols or probiotics for the management of arterial hypertension. Front
Physiol. 2016;7:448. https://doi.org/10.3389/fphys.2016.00448.
50. Tanaka H, Watanabe K, Ma M, et al. The effects of gamma-aminobutyric acid,
vinegar, and dried bonito on blood pressure in normotensive and mildly or
moderately hypertensive volunteers. J Clin Biochem Nutr. 2009;45(1):93–100.
https://doi.org/10.3164/jcbn.09-04.
51. Seravalle G, Grassi G. Obesity and hypertension. Pharm Res. 2017;122:1–7. https://
doi.org/10.1016/j.phrs.2017.05.013.
52. Wang Y, Wang QJ. The prevalence of prehypertension and hypertension among US
adults according to the new joint national committee guidelines: new challenges of
the old problem. Arch Intern Med. 2004;164(19):2126–2134. https://doi.org/
10.1001/archinte.164.19.2126.
53. Landsberg L, Aronne LJ, Beilin LJ, et al. Obesity-related hypertension: pathogenesis,
cardiovascular risk, and treatment: a position paper of The Obesity Society and the
American Society of Hypertension. J Clin Hypertens. 2013;15(1):14–33. https://doi.
org/10.1111/jch.12049.
54. Valdes DS, So D, Gill PA, Kellow NJ. Effect of dietary acetic acid supplementation on
plasma glucose, lipid profiles, and body mass index in human adults: a systematic
review and meta-analysis. J Acad Nutr Diet. 2021;121(5):895–914. https://doi.org/
10.1016/j.jand.2020.12.002.
55. Beh BK, Mohamad NE, Yeap SK, et al. Anti-obesity and anti-inflammatory effects of
synthetic acetic acid vinegar and Nipa vinegar on high-fat-diet-induced obese mice.
Sci Rep. 2017;7(1):6664. https://doi.org/10.1038/s41598-017-06235-7.
56. Fushimi T, Tayama K, Fukaya M, et al. Acetic acid feeding enhances glycogen
repletion in liver and skeletal muscle of rats. J Nutr. 2001;131(7):1973–1977.
https://doi.org/10.1093/jn/131.7.1973.
57. Hadi A, Pourmasoumi M, Najafgholizadeh A, Clark CCT, Esmaillzadeh A. The effect
of apple cider vinegar on lipid profiles and glycemic parameters: a systematic review
and meta-analysis of randomized clinical trials. BMC Complement Med Ther. 2021;21
(1):179. https://doi.org/10.1186/s12906-021-03351-w.
58. Korshøj M, Hannerz H, Frikke-Schmidt R, et al. Occupational lifting and risk of
hypertension, stratified by use of anti-hypertensives and age – a cross-sectional and
prospective cohort study. BMC Public Health. 2021;21(1):721. https://doi.org/
10.1186/s12889-021-10651-w.
H. Shahinfar et al. Complementary Therapies in Medicine 71 (2022) 102887

59. Robles NR, Macias JF. Hypertension in the elderly. Cardiovasc Hematol Agents Med
Chem. 2015;12(3):136–145. https://doi.org/10.2174/
1871525713666150310112350.
60. Lakatta EG, Cohen JD, Fleg JL, Frohlich ED, Gradman AH. Hypertension in the
elderly: age- and disease-related complications and therapeutic implications.
Cardiovasc Drugs Ther. 1993;7(4):643–653. https://doi.org/10.1007/bf00877817.
61. Del Giudice A, Pompa G, Aucella F. Hypertension in the elderly. J Nephrol. 2010;23
(Suppl. 15):S61–S71.