Content uploaded by Nicole J Kellow
Author content
All content in this area was uploaded by Nicole J Kellow on May 24, 2022
Content may be subject to copyright.
RESEARCH
Systematic Review
Effect of Dietary Acetic Acid Supplementation
on Plasma Glucose, Lipid Profiles, and Body
Mass Index in Human Adults: A Systematic
Review and Meta-analysis.
Daniela S. Valdes, MSc; Daniel So, APD; Paul A. Gill, PhD; Nicole J. Kellow, AdvAPD, CDE, PhD
ARTICLE INFORMATION
Article history:
Submitted 28 May 2020
Accepted 3 December 2020
Keywords:
Acetic acid
Vinegar
Diet therapy
Systematic review
Metabolic disease
2212-2672/Copyright ª2020 by the Academy of
Nutrition and Dietetics.
https://doi.org/10.1016/j.jand.2020.12.002
ABSTRACT
Background Acetic acid is a short-chain fatty acid that has demonstrated biomedical
potential as a dietary therapeutic agent for the management of chronic and metabolic
illness comorbidities. In human beings, its consumption may improve glucose regula-
tion and insulin sensitivity in individuals with cardiometabolic conditions and type 2
diabetes mellitus. Published clinical trial evidence evaluating its sustained supple-
mentation effects on metabolic outcomes is inconsistent.
Objective This systematic review and meta-analysis summarized available evidence on
potential therapeutic effects of dietary acetic acid supplementation via consumption of
acetic aciderich beverages and food sources on metabolic and anthropometric outcomes.
Methods A systematic search was conducted in Medline, Scopus, EMBASE, CINAHL
Plus, and Web of Science from database inception until October 2020. Randomized
controlled trials conducted in adults evaluating the effect of dietary acetic acid sup-
plementation for a minimum of 1 week were included. Meta-analyses were performed
using a random-effects model on fasting blood glucose (FBG), triacylglycerol (TAG),
high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycated hemoglobin
(HbA1c), body mass index (BMI), and body fat percentage. Statistical heterogeneity was
assessed by calculation of Q and I
2
statistics, and publication bias was assessed by
calculation of Egger’s regression asymmetry and Begg’s test.
Results Sixteen studies were included, involving 910 participants who consumed be-
tween 750 and 3600 mg acetic acid daily in interventions lasting an average of 8 weeks.
Dietary acetic acid supplementation resulted in significant reductions in TAG concen-
trations in overweight and obese but otherwise healthy individuals (mean difference
[MD] ¼20.51 mg/dL [95% confidence intervals ¼32.98, 8.04], P¼.001) and people
with type 2 diabetes (MD ¼7.37 mg/dL [10.15, 4.59], P<.001). Additionally, acetic
acid supplementation significantly reduced FBG levels (MD ¼35.73 mg/dL [63.79,
7.67], P¼.01) in subjects with type 2 diabetes compared with placebo and low-dose
comparators. No other changes were seen for other metabolic or anthropometric out-
comes assessed. Five of the 16 studies did not specify the dose of acetic acid delivered,
and no studies measured blood acetate concentrations. Only one study controlled for
background acetic acid-rich food consumption during intervention periods. Most
studies had an unclear or high risk of bias.
Conclusion Supplementation with dietary acetic acid is well tolerated, has no adverse
side effects, and has clinical potential to reduce plasma TAG and FBG concentrations in
individuals with type 2 diabetes, and to reduce TAG levels in people who are overweight
or obese. No significant effects of dietary acetic acid consumption were seen on HbA1c,
HDL, or anthropometric markers. High-quality, longer-term studies in larger cohorts are
required to confirm whether dietary acetic acid can act as an adjuvant therapeutic agent
in metabolic comorbidities management.
J Acad Nutr Diet. 2020;-(-):---.
CHRONIC METABOLIC DISORDERS—OBESITY, CAR-
diovascular disease, type 2 diabetes mellitus (T2DM),
and metabolic syndrome (MetS)—are the primary
causes of death worldwide, responsible for over 30
million (60%) annual deaths, a number expected to rise to 70%
by the end of 2020.
1,2
Good evidence supports dietary in-
terventions as first-line strategies for the management of
chronic and metabolic diseases.
3-5
Nevertheless,
ª2020 by the Academy of Nutrition and Dietetics. JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 1
pharmacological agents, including weight-reduction medi-
cations, lipid-lowering drugs, and anti-diabetic agents, are
widely used as adjunct long-term therapies to encourage
weight loss and improve metabolic function in individuals
with chronic cardiometabolic disease.
6,7
Although pharma-
cological agents consistently demonstrate significant im-
provements in circulating lipids, glucose tolerance, and body
fat reduction in controlled trials, undesirable medication side
effects such as fatigue, anxiety, headaches, gastrointestinal
disturbances, muscle pain, hypertension, and upper respira-
tory disorders are frequently reported as a result of their
sustained use.
7,8
Dietary interventions provide therapeutic
benefits comparable to medications, while avoiding drug-
associated side effects. The consumption of exogenous ace-
tic acid through dietary sources has been proposed as a
promising novel strategy for the prevention or management
of chronic metabolic dysfunction.
9,10
Acetic acid is a short-chain fatty acid produced in the colon
as a byproduct of microbial fermentation of dietary fiber, that
is, carbohydrates with a degree of polymerization greater
than 2 that fail to be hydrolyzed in the small intestine.
11,12
In
humans, acetic acid created by bacterial fermentation enters
the bloodstream and reaches the liver via the portal vein,
where it is converted to acetyl coenzyme A and used as an
energy source and as substrate for the synthesis of long-chain
fatty acids and cholesterol.
13
Between 50% and 70% of
colonic-derived acetic acid reaches the liver, whereas the
remaining 30% to 40% is released into circulation and be-
comes available for use by nonhepatic tissues.
14
Alternatively,
acetic acid may be absorbed via the upper gastrointestinal
tract after consumption of foods rich in natural acetic acid,
particularly vinegars.
15,16
Vinegar is produced from the bac-
terial fermentation of carbohydrates found in grapes (wine
vinegar), fruit (apple, cranberry vinegar), or other commonly
consumed foods (rice wine vinegar).
17
An alternative rich
source of acetic acid is kimchi—a traditional Korean condi-
ment commonly made from fermented cabbage and rad-
ishes.
18,19
Once in the systemic circulation, acetic acid is
detectable in the peripheral blood at micromolar concentra-
tions and may be altered by consumption of alcohol or a
high-fermentable fiber meal.
20,21
Acetic acid has demonstrated therapeutic potential for the
prevention or management of disorders of glucose and lipid
metabolism in rodent models. Acute and sustained acetic acid
ingestion can have several positive effects on mammalian
metabolism. Acetic acid consumption has been reported to
decrease hepatic glucose production while increasing hepatic
lipid oxidation
22
; improve beta-cell function, resulting in
increased insulin secretion
23
; increase hepatic and skeletal
muscle glucose use and enhance tissue glycogen repletion
24
;
encourage weight reduction; and improve circulating lipid
profiles.
25,26
Vinegar consumption in adults with T2DM re-
duces fasting and postprandial circulating glucose and en-
hances insulin secretion.
27
The promising therapeutic effects
gained from acetic acid consumption suggest it may repre-
sent a feasible adjunct therapy for the management of
metabolic diseases.
This systematic review summarizes available evidence
from randomized controlled clinical trials investigating the
therapeutic effects of sustained dietary acetic acid supple-
mentation on cardiometabolic and anthropometric outcomes
in both healthy individuals and people with chronic
metabolic conditions. The results of this review may assist in
determining the potential utility of dietary acetic acid con-
sumption as a nonpharmacological therapeutic agent for the
improvement of biomarkers associated with chronic meta-
bolic dysfunction.
METHODS
The current review was registered in the International Pro-
spective Register of Systematic Reviews in February 2018
(Registration No. CRD42018094178). It was designed in
accordance with the Cochrane Handbook for Systematic Re-
views of Interventions recommendations
28
and conducted in
accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) Statement.
29
Search Strategy
A literature search was performed in the electronic databases
MEDLINE, Scopus, EMBASE, CINAHL Plus, and Web of Science
from database inception to October 31, 2020, using a com-
bination of free text terms, synonyms, and subject headings
relevant to the objectives of this review in consultation with
an experienced systematic review librarian (Figure 1). A
multi-step search approach was taken to retrieve relevant
studies through additional hand-searching of reference lists,
searching conference abstracts, and review of the Interna-
tional Clinical Trials Register Search Portal and ClinicalTrials.
gov to identify ongoing trials. There was no date restriction in
the search strategy. The screening of articles was performed
independently by two review authors (D. S. V. and D. S.), with
disagreements resolved by consensus or a third reviewer (P.
A. G.).
Study Selection
Search results were merged into the systematic review soft-
ware package Covidence,
30
capable of automatic de-
duplication. Remaining references were screened for eligi-
bility using this software. Full-text articles of potentially
relevant studies were sought and reviewed. Study authors
were contacted by the primary author if additional data were
required to assess study eligibility or to conduct the quanti-
tative analysis.
RESEARCH SNAPSHOT
Research Question: Can supplementation with dietary acetic
acid act as an effective nonpharmacological therapeutic
strategy for metabolic comorbidities management?
Key Findings: This systematic review identified 16
randomized controlled trials published up to October 2020,
most of which had an unclear or high risk of bias. Studies
evaluated dietary acetic acid supplementation for up to 12
weeks on important metabolic and anthropometric markers
of 910 participants. Supplementation achieved clinically
relevant reductions in fasting blood glucose (FBG) and
triacylglycerol (TAG) levels in individuals with type 2
diabetes, and TAG reductions in people who were
overweight or obese. Higher-quality studies in larger cohorts
are warranted to definitively assess this research question.
RESEARCH
2JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
Studies were included if they met all of the following
criteria: 1) randomized controlled trial (RCT) design; 2)
conducted in adults (18 years of age) regardless of health
status; 3) intervention provided acetic acid (or acetate) sup-
plementation through a dietary source; 4) inclusion of either
a placebo or low-dose control group; 5) intervention period
lasting a minimum of 1 week; 6) measured at least one of the
following outcomes both at baseline and at the end of the
intervention period: fasting blood glucose (FBG) and tri-
acylglycerol levels (TAGs), high-density lipoprotein (HDL),
low-density lipoprotein (LDL), glycated hemoglobin (HbA1c),
body mass index (BMI) or body fat percentage; and 7) pub-
lished in English. Outcomes were measured as the difference
in end of intervention scores between the acetic acid sup-
plementation and comparator groups. Studies providing pure
acetic acid through nonfood sources via a pill or intravenous
injection were excluded from this review. Additionally,
studies solely investigating postprandial effects of acetic acid
consumption were excluded, because two published sys-
tematic reviews have previously evaluated postprandial ef-
fects of vinegar consumption on human adult metabolic
profiles.
27,31
Data Extraction and Risk of Bias Assessment
Data from included studies was extracted by one reviewer (D.
S. V.) and verified by a second (D. S.). Data extracted included:
country of publication, study design (duration, blinding, and
“washout”periods where applicable), participant character-
istics, and intervention details (dietary source of acetic
aciderich foods, comparator used, acetic acid quantity
consumed per day, time of day acetic acid sources were
consumed, and number of times these were ingested). Where
studies used a crossover design, and were thus of a within-
subjects nature, data for the intervention and placebo
Ovid Medline: 1 January 1982 to 31 October 2020
1. vinegar.tw.
2. Acetic Acid/
3. “acetic acid”.tw.
4. “diet* acetate”.tw.
5. AcOH.tw.
6. AcNA.tw.
7. Fermented.tw.
8. fermented foods/ or cultured milk products/ or kombucha tea/9. kombucha.tw.
10. “Apple cider vinegar”.tw.
11. vinaigrette.tw.
12. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11
13. “postprandial glucose”.tw.
14. “postprandial insulin”.tw.
15. “postprandial response”.tw.
16. “Postprandial level*”.tw.
17. HbA1c.tw.
18. Glycated Hemoglobin A/19. Insulin Resistance/20. “insulin sensitivity”.tw.
21. “insulin levels”.tw.
22. “serum glucose”.tw.
23. “circulating glucose”.tw.
24. “blood glucose”.tw.
25. “fast* glucose”.tw.
26. “HOMA*”.tw.
27. triglycerides/ or lipoproteins, hdl/ or lipoproteins, ldl/28. triacylglycerol.tw.
29. “plasma cholesterol”.tw.
30. “serum cholesterol”.tw.
31. homocysteine.tw.
32. Postprandial Period/33. CHOLESTEROL/34. 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26
35. 27 or 28 or 29 or 30 or 31 or 32 or 33
36. 34 or 35
37. 12 and 36
Figure 1. Database search strategy used in this systematic review to explore the effect of dietary acetic acid consumption vs
placebo/low-dose comparators on metabolic and anthropometric outcomes in adults.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 3
periods were pooled if no carry-over effects were reported in
the primary publication. Where studies involved multiple
intervention groups of different acetic acid doses, the highest
intervention dose was extracted.
The risk of bias of included studies was assessed indepen-
dently by two authors (D. S. V. and N. K.), using the Cochrane
Risk of Bias tool for assessment of RCTs.
32
Bias minimization
items included selection bias, performance bias, detection bias,
attrition bias, and reporting bias. Studies were evaluated to
have a “low risk,”“high risk,”or “unclear risk”based on the
Cochrane recommendations. This review assessed “other bias”
as financial or institutional conflicts of interest, failure to
measure intervention compliance, incorporation of additional
bioactive compounds as confounders in the evaluation of
acetic acid effects, and nonassessment of dietary intake during
lead-in, intervention, and washout periods.
Statistical Analyses
The treatment effects of selected outcomes were calculated
based on the differences in end of intervention values be-
tween the experimental and comparator groups. Variance
was calculated from the published standard deviation or
standard error values, with confidence intervals (CI) used
where these values were not available.
33
Where end of
intervention data was unable to be obtained, results were
described in text only. Review outcomes were further sepa-
rated into four subgroups specific to participant health sta-
tus: 1) healthy, 2) overweight or obese but otherwise healthy,
3) metabolic conditions that included MetS, prediabetes, or
hypercholesterolemia, and 4) T2DM.
Meta-analyses were performed where outcome subgroups
were quantitatively reported in at least two studies using
RevMan software.
34
The mean difference (MD) was used to
calculate effect sizes, with study data converted to the same
unit for each outcome where necessary
35
: data for FBG, TAGs,
HDL-cholesterol, and LDL-cholesterol was converted to mg/
dL units; and data for HbA1c and body fat was converted to
percentages. Data from the final reporting time point were
used for analysis; if data were not obtainable, then results
were narratively described in text only.
A random effects model (Dersimonian-Laird with inverse
variance weighting) was used to produce a pooled estimate of
the MD. The I
2
statistic was used to quantify the in-
consistencies between studies and subgroups, describing the
percentage of variability in effect sizes. Heterogeneity was
deemed significant if the I
2
statistic exceeded 50%.
36
Sensi-
tivity analyses were conducted to explore sources of statis-
tical heterogeneity, as well as for studies whose design or
results appeared inconsistent with other analyzed studies,
including large studies and studies with a high risk of bias.
For outcomes with 10 or more studies, publication bias was
assessed by calculation of Egger’s regression asymmetry test
and Begg’s test,
37,38
with P<.05 considered evidence of
small-study effects. Funnel plots were also constructed and
visually assessed for funnel plot asymmetry.
39
RESULTS
Characteristics of Included Studies
The flowchart of study identification and inclusion is detailed
in the PRISMA diagram (Fig 2). The initial database search
identified a total of 4246 studies. After duplicates were
removed and nonrelevant studies (n ¼2904) excluded, 76
studies were subjected to full text review. From these, 16
studies involving 910 participants comprehensively met in-
clusion criteria and were included.
40-55
From the 60 excluded
studies, the most common reasons for exclusion were
investigation of wrong intervention or route of administra-
tion (ie, delivery of pure acetic acid in the absence of a food/
fluid matrix through intravenous injections or pill ingestion)
(n ¼23) and postprandial data being solely analyzed after the
intervention (n ¼15). All 16 included studies were eligible for
quantitative assessment via meta-analysis.
Characteristics of included studies are detailed in Figure 3.
Articles retrieved were published between the years of 2007
and 2019. Studies were mostly conducted in the Republic of
Korea (n ¼4), followed by the United States (n ¼3), Iran (n ¼
3), and Pakistan (n ¼3). Of the remaining studies, one trial was
conducted in Japan, one in India, and another in Taiwan. A total
of 910 participants aged 23 to 72 years and with BMIs ranging
from 21.2 to 30.0 were investigated. Of the defined subgroups
specific for participant health status, two studies investigated
healthy individuals (n ¼172),
43,44
four investigated over-
weight or obese participants who were otherwise healthy (n ¼
245),
48,49,51,53
three
41,42,46
investigated individuals with meta-
bolic conditions such as prediabetes, MetS, or hypercholes-
terolemia (n ¼111), and six recruited people with T2DM (n ¼
342).
40,45,47,50,54,55
The health status of participants was not
reported in one study (n ¼40)
52
; however, as reported, TAG
and LDL baseline data were within the healthy adult range
(mean, 94 mg/dL and 111.2 mg/dL, respectively); it was
analyzed within the healthy individuals’subgroup. The dura-
tion of included studies ranged from 1 to 12 weeks, with most
interventions conducted using a parallel design (n ¼13).
Dietary sources of acetic acid were primarily vinegar-based
beverages, including apple cider vinegar, honey vinegar
syrup, white vinegar, pomegranate vinegar, cranberry vine-
gar, and red date vinegar. Fermented kimchi was the only
solid food base source of dietary acetic acid reported. Daily
acetic acid doses provided through dietary interventions
ranged from 750 mg to 3600 mg; however, precise quantities
of acetic acid delivered were not reported in 31% of included
studies (n ¼5).
42-44,48,52
Dietary acetic acid sources were
predominantly delivered with meals (n ¼12) once, twice, or
three times per day. The habitual dietary intake of partici-
pants at baseline was assessed in 12 studies.
40-45,48,49,51,53-55
Intervention adherence measurements and collection of di-
etary intake data during the intervention periods were
assessed in nine trials.
42-45,48,49,51,53,55
A run-in period was
included in five studies, lasting either 1,
51
2,
42,48,52
or 3
weeks.
49
All data obtained for quantitative analysis included
end of intervention values, with the exception of one study
46
for which the final reported time point (6 weeks) was used.
No studies reported adverse side effects after acetic acid
consumption via any type of dietary source. The outcome of
each meta-analysis performed is summarized in Table 1.
Fasting Blood Glucose
Thirteen studies investigated the effect of dietary acetic acid
intake on FBG (mg/dL) in participants who either were
healthy,
43,44
were overweight or obese,
48,49,51,53
had a meta-
bolic condition,
42,46
or had been diagnosed with
T2DM,
40,45,50,54,55
all of which were included in the meta-
RESEARCH
4JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
analysis (Fig 4). Dietary acetic acid supplementation did not
significantly reduce FBG levels in the healthy, overweight or
obese, or metabolic conditions subgroups. Four
40,45,50,55
of
five studies conducted in people with T2DM reported sig-
nificant decreases in FBG after acetic acid supplementation,
resulting in a significant overall intervention effect
(MD ¼35.73 mg/dL, P¼.01) and high within-group het-
erogeneity (I
2
¼98%) (to convert mg/dL to mmol/L, multiply
by 0.0555). Differences in FBG levels were less variable within
the healthy (MD ¼1.07 mg/dL, P¼.29, I
2
¼0%), overweight
and obese (MD ¼1.31 mg/dL, P¼.25, I
2
¼0%), and meta-
bolic conditions (MD ¼0.88 mg/dL, P¼.74, I
2
¼0%) sub-
groups. Sensitivity analysis (removal of one study at a time)
did not significantly alter the result. Statistical heterogeneity
(I
2
) within the T2DM subgroup was reduced from 98% to 41%
when the Nazni et al
55
data were removed, and was reduced
from 98% to 0% when data from both Nazni et al
55
and
Mahmoodi et al
50
were removed. Visual inspection of the
funnel plot (Fig 5) indicated potential publication bias for
studies involving participants with T2DM, but not for those
involving healthy participants, individuals with overweight
or obesity, or those with metabolic conditions. Egger’stest
was not significant for publication bias (P¼.902). Begg’s test
was significant for publication bias (P¼.014), but this sig-
nificance disappeared when the Nazni et al
55
and Mahmoodi
et al
50
studies (outliers on the funnel plot) were excluded
from the calculation (P¼.062).
Triacylglycerol
Nine studies investigated the effects of daily dietary acetic
acid intake on circulating TAG levels (mg/dL) in healthy,
44,52
overweight or obese individuals,
48,49,51
people with meta-
bolic conditions,
41
and subjects with T2DM
40,50,54
; eight were
included in the meta-analysis (Fig 6A). In overweight and
obese participants (n ¼222), dietary acetic acid supple-
mentation resulted in a statistically significant reduction in
TAG levels compared with placebo and low-dose compara-
tors (MD ¼20.5 mg/dL, P¼.001) with minimal statistical
heterogeneity (I
2
¼4%) (to convert mg/dL to mmol/L, divide
by 88.5). Of the three studies informing this result, only
Kondo et al
49
found statistically significant reductions in TAG
levels in obese individuals after 12 weeks of 1500 mg daily
acetic acid supplementation. In contrast, Kim et al
48
and Park
et al
51
found no significant reductions in TAG concentrations
after acetic acid intake in their trials (which were of shorter
duration), and it should be noted their study subjects were
primarily overweight rather than obese. Studies involving
individuals with T2DM (n ¼225) showed a small but sig-
nificant overall reduction in TAG levels (MD ¼7.37 mg/dL, P
<.001), with low heterogeneity between studies (I
2
¼0%).
Meta-analysis of studies involving healthy individuals (n ¼
101) indicated that dietary acetic acid supplementation had
no effect on TAG levels compared with comparators (MD ¼
0.73 mg/dL, P¼.92), with minimal statistical heterogeneity
detected (I
2
¼0%).
Records identified through
database searching
(n= 4239)
MEDLINE (n= 632)
Scopus (n= 1021)
EMBASE (n= 1508)
CINAHL (n= 214)
WEB OF SCIENCE (n= 864)
Identification
Records screened
(n= 2980)
Records after duplicates removed
(n=2980)
Additional records identified by
hand-searching reference lists of
included studies
(n= 7)
Eligibility
Included
Screening
Full-text articles excluded
(n= 60)
Not RCT (n= 4)
Only postprandial data analysed (n
= 15)
Wrong intervention or route of
administration (n= 23)
Abstract publication only (n = 12)
Did not repo rt on review outcomes
(n= 3)
Not original research (n= 3)
Records excluded
(n= 2904)
Studies included in
quantitative synthesis
(meta-analysis)
(n= 16)
Studies included in
qualitative synthesis
(n= 16)
Full-text articles
assessed for eligibility
(n= 76)
Figure 2. Flow diagram of the literature search and screening results for a systematic review of the effect of dietary acetic acid
supplementation on fasting plasma glucose, lipid profiles, and body mass index in adults.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 5
Author, year,
country
Participants Interventions RCT
a
Design
Participants
analyzed (N);
mean age; %
Males
Health status;
mean BMI
b
(kg/m
2
)
Acetate source
and amount;
acetic acid
delivered; daily
servings
Comparator;
daily dose;
acetate
present
(mg/d) Design Duration
Ali et al, 2018,
40
Pakistan
N¼55
Mean age:
intervention
46.4 y,
placebo 48.6 y
%Males:
intervention
46.4%,
placebo 48.1%.
T2DM
c
;
Mean BMI:
intervention 24.2,
placebo 23.3.
Red date
vinegar; 30 mL;
90 mg
One 30-mL
serving in the
morning or
before bedtime
without food
Honey
diluted in
water; 20 mL;
none
Parallel,
single-
blind
10
weeks
Ali et al, 2019,
41
Pakistan
N¼76
Mean age:
intervention
49.8 y,
placebo 50.4 y
%Males
intervention
20.5%,
placebo 18.9%
Mild
hypercholesterolemia
Mean BMI:
intervention 28.4,
placebo 26.8
Red date
vinegar; 30 mL,
90 mg.
One 30-mL
serving in the
morning or
before bedtime
without food
Placebo
drink,
unspecified
Parallel,
single-
blind
8 weeks
An et al, 2013,
42
Republic of
Korea
N¼21
Mean age: 45.9 y
%Males: 33.3%
Prediabetes or MetS
d
Mean BMI: 27.8
Fermented
kimchi; 300 g;
unknown
Three 100-g
servings with
meals
Fresh kimchi;
300 g;
unknown
Cross-
over,
not
blinded
8 weeks
per leg.
4-week
washout
Derakhshandeh-
Rishehri et al,
2014,
44
Iran
N¼72
Mean age:
intervention
28.3 y,
control 31.6 y
%Males
intervention
33.3%,
control 28%
Healthy
Mean BMI:
intervention 22.8,
control 25.3
Honey vinegar
syrup; 21.7g;
unknown
One 21.7g
serving mixed
in 250 mL
water mid-
morning or
early evening
Water; 25 mL;
none
Parallel,
not
blinded
4 weeks
Gheflati et al,
2019,
45
Iran
N¼62
Mean age:
intervention
49.5 y,
control 52.1 y
%Males:
intervention
31.3%,
control 33.3%
T2DM and
dyslipidemia
Mean BMI:
intervention 29.0,
control 28.9
Apple cider
vinegar; 2 0mL;
1000 mg.
Two 10-mL
servings,
before lunch
and dinner
No
intervention
Parallel,
not
blinded
8 weeks
(continued on next page)
Figure 3. Sample and study design characteristics of the 16 included randomized controlled trials investigating the effect of
dietary acetic acid supplementation compared with placebo/low-dose comparators on metabolic and anthropometric outcomes
in adults.
RESEARCH
6JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
Author, year,
country
Participants Interventions RCT
a
Design
Participants
analyzed (N);
mean age; %
Males
Health status;
mean BMI
b
(kg/m
2
)
Acetate source
and amount;
acetic acid
delivered; daily
servings
Comparator;
daily dose;
acetate
present
(mg/d) Design Duration
Jasbi et al,
2019,
53
USA
e
N¼45
Mean age:
intervention
29.6 y,
comparator
30.1 y
%Males:
intervention
95.2%,
comparator
87.5%
Overweight
Mean BMI:
intervention 27.8,
comparator 28.5
Red wine
vinegar, 60 mL;
3600 mg.
Two 30-mL
servings
diluted in water
with meals
Apple cider
vinegar pills,
45 mg.
One pill (22.5
mg acetic
acid) twice
with meals
Parallel,
not
blinded
8 weeks
Johnston et al,
2013,
46
USA
N¼14
Mean age:
intervention
48.1 y
comparator
43.9 y
%Males: total 7%,
not provided
per group
Prediabetes
Mean BMI:
intervention 29.2,
comparator 27.7
Apple cider
vinegar; 30 mL;
1500 mg.
Two servings of
commercially
available
vinegar drink
with meals
Vinegar pill;
80 mg.
One pill (40
mg acetic
acid) twice
with meals
Pilot,
not
blinded
12
weeks.
Follow-
up data
up to
week 6
Johnston et al,
2009,
47
USA
N¼15
Mean age:
intervention
67.1 y
comparator
62.9 y
%Males:
intervention
20%,
comparator 13%
T2DM
Mean BMI:
Not reported
White vinegar;
30 mL; 1400
mg. Taken
once with a
meal
One 30-mL
serving
ingested with a
meal
Vinegar pill;
15 mg/d. One
pill taken
with a meal
Parallel,
not
blinded
12
weeks
Kausar et al,
2019,
54
Pakistan
N¼110
Mean age:
intervention 51 y,
placebo 50 y
%Males:
intervention 38%
placebo 47%
T2DM
Mean BMI:
intervention 37.9
placebo reported as
20-30
Apple cider
vinegar, 15 mL,
700 mg
One 15-mL
serving diluted
in 200 mL
water taken
before bedtime
Artificial
apple cider
vinegar
flavor, 15 mL,
none
One 15-mL
serve diluted
in 200 mL
water taken
before
bedtime
Parallel,
single
blind
12
weeks
(continued on next page)
Figure 3. (continued) Sample and study design characteristics of the 16 included randomized controlled trials investigating the
effect of dietary acetic acid supplementation compared with placebo/low-dose comparators on metabolic and anthropometric
outcomes in adults.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 7
Author, year,
country
Participants Interventions RCT
a
Design
Participants
analyzed (N);
mean age; %
Males
Health status;
mean BMI
b
(kg/m
2
)
Acetate source
and amount;
acetic acid
delivered; daily
servings
Comparator;
daily dose;
acetate
present
(mg/d) Design Duration
Kim et al,
2011,
48
Republic of
Korea
N¼22
Mean age: 38.6 y,
%Males: 32%
Overweight and
obese
Mean BMI: 27.7
Fermented
kimchi; 300 g;
unknown
Three 100-g
servings with
meals
Fresh kimchi;
300g;
unknown
Cross-
over,
not
blinded
4 weeks
per leg
2-week
washout
Kondo et al,
2009,
49
Japan
N¼101
Mean age:
intervention
43.4 y,
placebo 44.1 y
%Males
intervention
61%,
placebo 64%
Obese
Mean BMI:
intervention 27.0,
placebo 26.9.
Vinegar drink;
500 mL; 1500
mg.
Test beverage
consumed in
two equal
portions (250
mL) after
breakfast and
dinner
Placebo
drink; 500
mL; none
Parallel,
double
blind
12
weeks
Mahmoodi et al,
2013,
50
Iran
N¼60
Mean age:
Reported as 30-
60 y for both
groups
%Males
Not reported
T2DM
Mean BMI:
Not reported
Vinegar (type
not specified);
15 mL; 750 mg
One 15-mL
vinegar drink
with lunch
No
intervention
Parallel,
double-
blind
4 weeks
Nazni et al,
2015,
55
India
N¼40
Mean age:
intervention
42.3 y,
control 50.1 y
% Males
intervention
50%,
control 60%
T2DM
Mean BMI:
intervention 27.6,
control 28.1
Apple cider
vinegar, 30 mL,
unknown.
Two 15-mL
servings before
breakfast and
dinner
No
intervention
Parallel,
not
blinded
12.8
weeks
Park et al,
2014,
51
Republic of
Korea
N¼77
Mean age:
intervention 41 y
placebo 42 years
%Males:
intervention 0%,
placebo 0%
Overweight
Mean BMI:
intervention 28.9,
placebo 28.0
Pomegranate
vinegar; 200
mL; 1500 mg.
Two 100-mL
test pouches
with breakfast
and dinner
Placebo
drink; 200
mL; none
Parallel,
double
blind
8 weeks
(continued on next page)
Figure 3. (continued) Sample and study design characteristics of the 16 included randomized controlled trials investigating the
effect of dietary acetic acid supplementation compared with placebo/low-dose comparators on metabolic and anthropometric
outcomes in adults.
RESEARCH
8JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
BMI and Body Fat Percentage
Seven studies
42,43,48,49,51,53,55
investigated the effect of acetic
acid consumption on BMI, four of which were studies
conducted in overweight or obese participants
(n ¼267)
48,49,51,53
and were suitable for meta-analysis (Fig
6B). In these individuals, daily dietary acetic supplementa-
tion did not result in significant reductions in mean BMI
compared with placebo or low-dose comparators
(MD ¼0.22, P¼.59), with moderate statistical heteroge-
neity detected (I
2
¼41%). No significant differences in BMI
were reported in healthy individuals after daily dietary
acetic acid intake (P>0.05)
43
.Anet al
42
also found no
significant reduction in BMI in individuals with prediabetes
after consumption of fermented kimchi (P¼.27). In
contrast, a single study
55
conducted in 40 subjects with
T2DM reported a significant reduction in BMI after daily
consumption of 30 mL apple cider vinegar for 3 months
(MD ¼2.40, P<.001).
The effect of dietary acetic acid supplementation on
total body fat percentage was assessed in six of these
studies,
42,43,48,49,51,53
with three trials conducted in over-
weight or obese individuals suitable for meta-anal-
ysis
48,49,53
(n¼190). Meta-analyses indicated no
difference in body fat percentage after dietary acetic acid
supplementation vs comparators (MD ¼0.04 %, P¼.96),
with minimal heterogeneity detected (I
2
¼0%) (Table 1).
In agreement with no changes in BMI, there was no sig-
nificant reduction in body fat percentage in healthy in-
dividuals after dietary acetic acid intervention (n ¼
100).
43
An et al
42
also reported no significant body fat
percentage reduction (P¼.34) after daily fermented
kimchi consumption for 8 weeks in individuals with
prediabetes.
HDL-Cholesterol
Nine studies investigated the effect of daily dietary acetic
acid supplementation on circulating HDL-cholesterol
levels (mg/dL), with eight studies undergoing meta-
analysis in participants who were either healthy,
43,44
overweight or obese,
48,49,51
or diagnosed with
T2DM
40,50,54
(Fig 7A). Meta-analysis showed no signifi-
cant increases in HDL-cholesterol levels in healthy sub-
jects (MD ¼0.24 mg/dL, P¼0.94, n ¼161), people with
overweight or obesity (MD ¼0.31 mg/dL, P¼.84, n ¼
222), or individuals with T2DM (MD ¼1.75 m g/ dL, P¼
.47, n ¼225) (to convert mg/dL to mmol/L, divide by
38.6). High heterogeneity was observed in the healthy
and T2DM subgroups (I
2
¼70% and 90%, respectively).
Contrary to the results of others, Ali et al
41
found a small
but significant increase in HDL-cholesterol after dietary
acetic acid supplementation in people with hypercholes-
terolemia after 8 weeks (MD ¼4.10 mg/dL, P¼.03, n ¼
76).
LDL-Cholesterol
Nine studies investigated the effects of dietary acetic acid
supplementation on circulating LDL-cholesterol levels
(mg/dL) in healthy,
43,44,52
overweight or obese partici-
pants,
48,49,51
individuals with metabolic conditions
41
and
people with T2DM,
40,50,54
eight of which were suitable for
meta-analysis (Fig 7B). Studies assessing LDL-cholesterol
Author, year,
country
Participants Interventions RCT
a
Design
Participants
analyzed (N);
mean age; %
Males
Health status;
mean BMI
b
(kg/m
2
)
Acetate source
and amount;
acetic acid
delivered; daily
servings
Comparator;
daily dose;
acetate
present
(mg/d) Design Duration
Wang et al,
2007,
52
Taiwan
N¼40
Mean age:
Not reported
%Males:
Not reported
Unknown
Mean BMI:
Not reported
Cranberry
vinegar; 400
mL; unknown.
Two 200-mL
servings,
ingestion time
not specified
Placebo
drink; 400
mL; none
Parallel,
not
blinded
10
weeks
a
RCT ¼randomized controlled trial.
b
BMI ¼body mass index.
c
T2DM ¼type 2 diabetes mellitus.
d
MetS ¼metabolic syndrome.
e
USA ¼United States of America.
Figure 3. (continued) Sample and study design characteristics of the 16 included randomized controlled trials investigating the
effect of dietary acetic acid supplementation compared with placebo/low-dose comparators on metabolic and anthropometric
outcomes in adults.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 9
in healthy (MD ¼0.63 mg/dL, P¼.86, n ¼201) and
overweight or obese individuals (MD ¼2.40 mg/dL, P¼
0.55, n ¼222) reported no effect of dietary acetic acid
supplementation between intervention and comparator
groups, with low heterogeneity within subgroups (I
2
¼0%
for both) (to convert mg/dL to mmol/L, divide by 38.6).
Additionally, meta-analyses indicated no significant
change in LDL-cholesterol levels in participants with
T2DM (MD ¼11. 0 4 mg/ d L, P¼0.21, n ¼225) and high
heterogeneity within the subgroup (I
2
¼88%). In contrast,
a study conducted by Ali and colleagues
41
reported a
significant reduction in LDL-cholesterol after acetic acid
consumption in people with hypercholesterolemia after 8
weeks (MD ¼45.20 ng/dL, P<.001, n ¼76). Statistical
heterogeneity (I
2
) within the type 2 diabetes subgroup
was reduced from 88% to 19% when the Ali et al
40
data
were removed. Visual inspection of the funnel plot (Fig 5)
indicated potential publication bias for the study
involving participants with metabolic conditions, but not
for those involving healthy participants, individuals with
overweight or obesity, or those with T2DM. Begg’stest
was not significant for publication bias (P¼.93), and
Egger’s regression asymmetry test was not significant
(P¼.06).
HbA1c
The effect of acetic acid supplementation on HbA1c levels (%)
was investigated in six studies involving individuals with
Table 1. Statistical summary of metabolic and anthropometric outcomes reported in 2 trials per subgroup from the 16
included randomized controlled trials comparing dietary acetic acid consumption with placebo or low-dose comparators in
adults. Data underwent meta-analysis using a random-effects model and are presented as mean difference (MD) and 95%
confidence interval (95% CI). Statistical heterogeneity was assessed and quantified by the Q and I
2
statistics
Outcome Subgroup
Studies included
in meta-analysis N
Results Heterogeneity
Mean difference
(MD) [95% CI]
Overall
effect (P)
c
2
test
(Q) P
I
2
[95% CI]
FBG
a
(mg/dL) Healthy 2
43,44
161 1.07 [3.04, 0.90] .29 0.58 .45 0% [0,0]
Overweight or
obese
4
48,49,51,53
267 1.31 [3.54, 0.92] .25 2.67 .45 0% [0, 85]
Metabolic
conditions
2
42,46
56 0.88 [6.15, 4.40] .74 0.02 .88 0% [0,0]
T2DM
b
5
40,45,50,54,55
327 35.75 [63.79, 7.67] <.001 198.8 <.001 98% [97, 99]
TAG
c
(mg/dL) Healthy 2
44,52
101 0.73 [14.45, 15.92] .92 0.43 .51 0% [0, 0]
Overweight or
obese
3
48,49,51
222 20.51 [32.98, 8.04] .001 4.51 .10 4% [0, 87]
T2DM 3
40,50,54
225 7.37 [10.15. 4.59] <.001 0.38 .83 0% [0, 82]
HDL
d
(mg/dL) Healthy 2
43,44
161 0.24 [6.13, 6.61] .94 3.37 .07 70% [0, 93]
Overweight or
obese
3
48,49,51
222 0.31 [3.31, 2.68] .84 0.73 .70 0% [0, 91]
T2DM 3
40,50,54
225 1.75 [3.02, 6.52] .47 20.06 <.001 90% [50, 93]
LDL
e
(mg/dL) Healthy 3
43,44,52
201 0.63 [7.45, 6.18] .86 0.19 .91 0% [0, 65]
Overweight or
obese
3
48,49.51
222 2.40 [10.26, 5.47] .55 0.42 .81 0% [0, 84]
T2DM 3
40,50,54
225 11.04 [28.37, 6.30] .21 16.63 <.001 88% [69, 95]
HbA1c
f
(%) T2DM 5
40,47,50,54,55
280 1.40 [2.95, 0.16] .08 77.27 <.001 95% [91, 97]
BMI
g
(kg/m
2
) Overweight or
obese
4
48,49,51,53
267 0.22 [1.03, 0.58] .59 5.12 .16 41% [0, 80]
Body fat (%) Overweight or
obese
3
48,49,53
190 0.04 [1.67, 1.76] .96 1.33 .51 0% [0, 95]
a
FBG ¼fasting blood glucose (to convert mg/dL to mmol/L, multiply by 0.0555 ).
b
T2DM ¼type 2 diabetes mellitus.
c
TAG ¼triacylglycerol (to convert mg/dL to mmol/L, divide by 88.5).
d
HDL ¼high-density lipoprotein (to convert mg/dL to mmol/L, divide by 38.6).
e
LDL ¼low-density lipoprotein (to convert mg/dL to mmol/L, divide by 38.6).
f
HbA1c ¼glycated hemoglobin.
g
BMI ¼body mass index.
RESEARCH
10 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
metabolic conditions or T2DM,
40,41,47,49,50,54
five of which were
suitable for meta-analysis (Table 1). Dietary acetic acid supple-
mentation did not have a significant effect on glycated hemo-
globin levels in participants with T2DM (MD ¼1.40%, P¼.08,
n¼280), with high interstudy heterogeneity detected (I
2
¼95%).
Sensitivity analysis did not significantly alter the result. Statis-
tical heterogeneity (I
2
) within the T2DM subgroup was reduced
from 95% to 56% when the Nazni et al
55
data were removed.
Risk of Bias of Included Studies
The risk of bias of included studies was evaluated by the
Cochrane Risk-of-Bias tool
32
(Figure 8). Most of the included
studies had either a high (n ¼10) or unclear (n ¼4) risk of
bias. Only two studies
51,53
were assessed to have a low risk of
bias. Six of the 16 studies reported the use of blinding of both
participants and research personnel, nine assessed baseline
dietary intake, and none evaluated circulating plasma levels
of acetic acid. Additionally, only seven studies reported an
intention-to-treat analysis,
40,41,44,45,51,53,54
and only one
53
evaluated the potential confounding effects of other bioac-
tive compounds that were administered in parallel with
foods or beverages rich in natural acetic acid.
Given the RCT study design of the included trials, the
CONSORT Statement outlining clear reporting guidelines for
RCTs was first published in 1996 and updated in 2010.
56,57
Because most studies in this review were published after
2010, inclusion of a comprehensive Methods section
addressing the key criteria of the CONSORT statement would
have been ideal.
DISCUSSION
Preclinical studies in rodents have demonstrated that
increasing dietary acetic acid delivery has potential to
improve metabolic outcomes.
22,24,26,58-60
Acute supplemen-
tation in humans has been shown to reduce postprandial
glucose and insulin responses
7,27,31,61
; however, little evi-
dence supports the use of long-term acetic acid supplemen-
tation to modify metabolic disease markers. This review
summarized clinical trials exploring the potential of sus-
tained dietary acetic acid supplementation as a therapeutic
strategy for the improvement of metabolic and anthropo-
metric markers in healthy individuals and those with chronic
disease. Sixteen published randomized controlled trials
40-54
involving 910 participants were identified and included
healthy individuals, people who were overweight or obese
but otherwise healthy, individuals with metabolic conditions
(including MetS, prediabetes, and hypercholesterolemia), and
people with T2DM. Meta-analyses showed that
Figure 4. Effect of dietary acetic acid supplementation on fasting blood glucose levels (mg/dL) in healthy individuals, people who
are overweight or obese, subjects with metabolic conditions, or those with type 2 diabetes compared with placebo or low-dose
comparators. Significant effect estimate shown for the type 2 diabetes subgroup. Mean differences (MD) (95% confidence in-
tervals) calculated via a random-effects model are shown.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 11
Figure 5. a) Funnel plot of individual studies indicating the effect of dietary acetic acid consumption vs placebo/low-dose com-
parators on fasting plasma glucose (mg/dL) in healthy subjects, people who are overweight or obese, individuals with metabolic
conditions, or those with type 2 diabetes. Mean differences (MD) for individual studies are plotted against the standard error of the
mean difference (SE[MD]) to estimate publication bias. b) Funnel plot of individual studies indicating the effect of dietary acetic acid
consumption vs placebo/low-dose comparators on low-density lipoprotein (LDL)-cholesterol (mg/dL) in healthy subjects, people
who are overweight or obese, individuals with metabolic conditions, or those with type 2 diabetes. Mean differences (MD) for
individual studies are plotted against the standard error of the mean difference (SE[MD]) to estimate publication bias.
RESEARCH
12 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
Figure 6. a) Effect of dietary acetic acid supplementation on triacylglycerol concentrations (mg/dL) in healthy individuals, people
who are overweight or obese, subjects with metabolic conditions, or those with type 2 diabetes compared with placebo or low-
dose comparators. Significant effect estimates shown for overweight or obese and type 2 diabetes subgroups. Mean differences
(MD) (95% confidence intervals [CIs]) calculated via a random-effects model are shown. b) Effect of dietary acetic acid supple-
mentation on body mass index (BMI) in individuals who are overweight or obese, subjects with metabolic conditions, or people
with type 2 diabetes compared with placebo or low-dose comparators. Significant effect estimate shown for one trial conducted in
people with type 2 diabetes. Mean differences (MD) (95% CIs) calculated via a random-effects model are shown.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 13
Figure 7. a) Effect of dietary acetic acid supplementation on HDL concentrations (mg/dL) in healthy individuals, subjects who are
overweight or obese, people with metabolic conditions, or those with type 2 diabetes compared with placebo or low-dose
comparators. Significant effect estimate shown for one trial conducted in people with metabolic conditions (hypercholesterole-
mia). Mean differences (MD) (95% confidence intervals [CIs]) calculated via a random-effects model are shown. b) Effect of dietary
acetic acid supplementation on LDL concentrations (mg/dL) in healthy individuals, people who are overweight or obese, or subjects
with metabolic conditions compared with placebo or low-dose comparators. Significant effect estimate shown for one trial con-
ducted people with metabolic conditions (hypercholesterolemia). Mean differences (MD) (95% CIs) calculated via a random-effects
model are shown.
RESEARCH
14 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
supplementation of dietary acetic acid led to significant re-
ductions in fasting blood glucose in people with T2DM, as
well as reductions in TAG concentrations in people with
T2DM and individuals who were overweight or obese. Acetic
acid supplementation did not significantly impact glycated
hemoglobin or body fat percentage in any of the populations
evaluated.
Sustained dietary supplementation of acetic acid led to
significantly lower fasting blood glucose in the T2DM group
compared with placebo, without having a significant effect in
healthy individuals, people with overweight or obesity, or
those with metabolic conditions (Fig 4). Elevations in plasma
acetic acid have been associated with normalization of blood
glucose homeostasis,
61,62
optimization of hepatic and skeletal
muscle glucose handling,
63
and increased insulin sensitivity.
64
Indeed, the effect of dietary acetic acid supplementation on
FBG levels in individuals with T2DM is consistent with acute
studies that report improved regulation of glucose and insulin
levels in adults with metabolic dysfunction and T2DM after
acute vinegar consumption.
27,65
The mean difference
of 35.73 mg/dL seen in this meta-analysis also suggests that
longer-term supplementation reduces FBG to a greater extent
than that seen after acute supplementation.
66
Aprimary
mechanism through which acetic acid is proposed to have
therapeutic action is via binding of G proteinecoupled re-
ceptor 43 (GPR43), which is expressed on human peripheral
blood mononuclear cells, adipose cells, and in colonic cells, of
which acetic acid is a strong activator at physiological con-
centrations of 50 to 200
m
mol/L.
67-69
Ligation to GPR43 by
acetic acid in the colonic epithelium results in increased
secretion of glucagon-like peptide-1 (GLP-1), a hormone that
promotes insulin action in muscle and adipose tissue and
consequently enhances insulin sensitivity.
11,70
Moreover, the
hormone GLP-1 is also responsible for indirectly regulating
blood glucose levels by inhibiting excessive glucagon secretion
and increasing glucose-dependent insulin secretion in the
pancreas.
71
Similarly, increased GLP-1 production was
observed in individuals with T2DM who achieved a significant
reduction in FBG after 12 weeks of a high-fiber dietary inter-
vention that increased acetic acid production.
72
The studies analyzed in this review did not report plasma
acetic acid concentrations after dietary supplementation.
Consequently, ascertaining whether plasma acetic acid
levels may have increased sufficiently to have a physiolog-
ical effect and whether outcomes observed can be directly
attributed to dietary acetic acid supplementation is difficult.
Consumption of a 100-mL vinegar drink containing 750 mg
acetic acid may increase plasma acetic acid concentrations
from 140 to 349
m
mol/L within 15 minutes.
73
However,
levels return to baseline within 60 minutes, suggesting that
regular consumption throughout the day may be needed to
achieve metabolic effects. Indeed, most studies reported in
this review instructed participants to consume vinegar 2 to
3 times per day alongside main meals, which is unlikely to
keep plasma acetic acid levels elevated throughout the day.
Because acetic acid levels within the body are tightly
regulated, acetic acid metabolism by peripheral tissues may
increase in response to increased delivery, as observed after
hepatic metabolism of ethanol, which releases acetate into
the peripheral circulation.
74
These metabolic changes in
response to sustained delivery may result in rapid clearance
of acetic acid from the peripheral blood but also could
contribute to favorable changes in peripheral tissue
metabolism.
Meta-analyses conducted in this review found that dietary
acetic acid supplementation resulted in statistically signifi-
cant reductions in TAG levels overweight and obese in-
dividuals who were otherwise healthy and people with
TD2M, compared with controls (Fig 6a, Table 1). The greatest
reduction in TAG levels observed was 32.80 mg/dL after 12
weeks of 1,500 mg/day acetic acid ingestion in an obese
population,
49
with the average decrease among studies in
overweight and obese individuals being 20.51 mg/dL.
Increased exogenous acetic acid delivery may have exerted
direct effects on circulating TAG levels by stimulating fat
oxidation through engagement of GPR43 on the surface of
white adipose tissue,
75,76
with subsequent reductions in
insulin-mediated fatty acid uptake directly contributing to
the suppression of fat accumulation.
64
Furthermore, obese
individuals have been reported to have significantly
decreased acetic acid turnover compared with healthy sub-
jects, which may explain the variable effects of dietary acetic
acid supplementation between populations.
77
Given that
vinegar consumption has been reported to increase satiety
and thus help in the regulation of body weight,
9
it is sur-
prising that no significant reductions in anthropometric
outcomes within the overweight and obese participant sub-
group were observed in this review (Fig 6B, Table 1). How-
ever, analyzed studies did not control for altered background
dietary intake, and most did not report dietary intake by
subjects during the intervention periods, which may have
confounded results.
The clinical relevance of the statistically significant changes
to metabolic markers seen in the meta-analyses conducted in
this review also must be considered. Reductions in circulating
TAG concentrations by 88.5 mg/dL are associated with a 12%
decrease in cardiovascular events and all-cause mortality in
adults,
78
whereas the same 88.5 mg/dL increment in circu-
lating TAG has been associated with cardiovascular risk in-
creases of 14% in men and 37% in women.
79
Therefore,
despite statistical significance, the reductions in TAG levels
observed (20.5 mg/dL in overweight and obese individuals
and 7.4 mg/dL in people with T2DM) offer only modest
clinical relevance, with possible clinical implications if stable
reductions in TAG were able to be maintained through
continued supplementation. Furthermore, statistically sig-
nificant reductions in FBG (35.73 mg/dL) observed in the
T2DM subgroup did follow a similar trend of reduced HBA1c
in this subgroup (1.40%, P¼.08), suggesting that continued
supplementation beyond the intervention period may result
in clinical improvement to disease. However, longer-term
follow-up of HBA1c levels in people with T2DM over the
course of several months (eg, 4-6 months) is needed to assess
the clinical relevance of acetic acid supplementation.
80
Assessment of metabolic changes within each individual
also may assist to identify patients who may receive clinical
benefits from such intervention.
A high degree of heterogeneity was observed in a number
of the study outcomes summarized in this review, and most
of the included studies were judged to have a high risk of
bias. Consequently, the results of some outcomes should be
interpreted with caution, particularly the significant decrease
in FBG reported in people with T2DM after acetic acid sup-
plementation. The significant degree of heterogeneity
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 15
observed (I
2
¼98%) could be attributed to several factors.
First, a range of different dietary sources were used to deliver
acetic acid. Dietary acetic acid was predominantly provided
through vinegar drinks, including apple cider vinegar,
45,46
honey vinegar syrup,
44
white vinegar,
47
pomegranate vine-
gar,
51
cranberry vinegar,
52
date vinegar,
40,41
and unspecified
vinegar drinks
49,50
; or through servings of fermented
kimchi.
42,43,48
These dietary sources not only naturally
contain differing levels of acetic acid, but they contain other
bioactive compounds such as lactic, malic, and citric acid, as
well as phenolic compounds, predominantly gallic acid,
catechin, and chlorogenic acid, which may have confounded
Study
Author/year
Risk of
bias
Bias Minimization Items
a
1
b
2
c
3
d
4
e
5
f
6
g
Other
Ali et al,
2018
40
Unclear þ?þ?þ? Funding and sponsorship free from bias
Ali et al,
2019
41
High þ?þ?þ Funding and sponsorship free from bias Significant
differences between placebo and intervention groups
at baseline not accounted for in statistical analyses.
Authors reported within-group changes rather than
between-group differences in outcomes.
An et al,
2013
42
High ? ? ? ? þþ Unclear whether funding and sponsorship free from bias
Choi et al,
2013
43
Unclear ? ? þ?þ? Unclear whether funding and sponsorship free from bias
Derakhshandeh-
Rishehri
et al, 2014
44
High ? ? ? ? þþ Funding and sponsorship free from bias Outcomes
possibly related to honey rather than vinegar
Gheflati et al,
2019
45
Unclear þ???þþ Funding and sponsorship free from bias
Jasbi et al,
2019
53
Low þþ?þþþFunding and sponsorship free from bias
Johnston et al,
2013
46
High ? ? þ?? Funding and sponsorship free from bias
Johnston et al,
2009
47
High ? ? ? ? ? þFunding and sponsorship free from bias
Published as a brief report, with limited methodological
information provided
Kausar et al,
2019
54
High þ??Unclear whether funding and sponsorship free from bias
Focus on within-groups analysis rather than between-
groups analysis
Clinical trial registered retrospectively
Kim et al, 2011
48
High ??? Funding and sponsorship free from bias.
Kondo et al,
2009
49
Unclear ? ? þþþ? Unclear whether funding and sponsorship free from bias
Mahmoodi
et al, 2013
50
High ? ? ? ? ? Unclear whether funding and sponsorship free from bias
Nazni et al,
2015
55
High þ???þ? Unclear whether funding and sponsorship free from bias
(continued on next page)
Figure 8. Risk of bias summary for included studies investigating the effect of dietary acetic acid supplementation vs placebo/low-
dose comparators on fasting glucose, lipid levels, and body composition in adults. Authors’judgments are shown for each risk of
bias item for all included trials, according to the Cochrane Risk-of-Bias tool.
33
RESEARCH
16 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
the effects observed.
18,81
Ideally, white vinegar should have
been used to deliver acetic acid, because it is distilled and
does not contain any other bioactive compounds.
82
Second,
study participants were not instructed to avoid foods rich in
natural acetic acid or fermentable fibers during run-in,
intervention, or washout periods in any of the included
studies. This is relevant because a standard serving of kimchi,
kombucha, or fermented cucumber pickles may provide
equivalent or greater amounts of acetic acid.
83,84
Finally, it is
also possible that short-chain fatty acids produced through
the colonic fermentation of dietary fibers could have elicited
the physiological effects shown.
11,16
These study limitations
have highlighted the necessity for future studies to account
for potentially confounding bioactive molecules and how
these affect blood acetic acid levels to reduce bias and more
clearly attribute study outcomes to dietary acetic acid
supplementation.
CONCLUSION
The results from this review suggest that dietary acetic acid
supplementation may offer the most benefittothosewho
are overweight or obese or have T2DM. However, the
interpretation of findings for metabolic and anthropometric
outcomes is challenging, given the high risk of bias of
included studies, poor study design, heterogeneity of di-
etary sources, and limited study size. Nevertheless, dietary
supplementation remains a desirable, less-invasive
approach compared with intravenous or colonic acetic
acid infusion. Results summarized in this review alongside a
growing pool of preclinical evidence propose a role for
acetic acid as a circulating glucose, lipid, and adipose tissue
regulator, and may hold promise as a potential future
therapy for the management of chronic and metabolic dis-
ease. Further investigation of the potential benefits of sus-
tained dietary acetic acid consumption is required, using
well-designed RCTs.
References
1. Mendis SAT, Bettcher D, Branca F, et al. World Health Organization
Global Status Report on Noncommunicable Diseases. 2014. Accessed
February 12, 2019, https://apps.who.int/iris/bitstream/handle/1
0665/148114/9789241564854_eng.pdf.
2. Yach D, Hawkes C, Gould C, Hofman KJ. The global burden of chronic
diseases: Overcoming impediments to prevention and control. JAMA.
2004;291(21):2616-2622.
3. World Health Organization. Diet, nutrition and the prevention of
chronic diseases. 2003. World Health Organization Technical Report
Series No. 916. 2003:1-60. Accessed February 5, 2019. https://www.
who.int/dietphysicalactivity/publications/trs916/en/
4. O’Keefe JH, Gheewala NM, O’Keefe JO. Dietary strategies for
improving post-prandial glucose, lipids, inflammation, and cardio-
vascular health. J Am Coll Cardiol. 2008;51(3):249-255.
PRACTICE IMPLICATIONS
What Is the Current Knowledge on This Topic?
Study
Author/year
Risk of
bias
Bias Minimization Items
a
1
b
2
c
3
d
4
e
5
f
6
g
Other
Park et al,
2014
51
Low þþþþþþFunding and sponsorship free from bias Outcomes
possibly related to pomegranate rather than vinegar
Wang et al,
2007
52
High ? ? ? ? þ? Unclear whether funding and sponsorship free from bias
Outcomes possibly related to cranberry rather than
vinegar
a
Bias minimization items: “þ”¼response of “yes”to use of the bias minimization item; “”¼response of “no”to use of the bias
minimization item; “?”¼response of “uncertain”to the use of the bias minimization item. Trials receiving a “þ”response for
most items are likely to have a low risk of bias.
b
1. Random sequence generation (selection bias).
c
2. Allocation concealment (selection bias).
d
3. Blinding of participants and personnel (performance bias).
e
4. Blinding of outcome assessment (detection bias).
f
5. Complete outcome data (attrition bias).
g
6. Nonselective reporting (reporting bias).
Figure 8. (continued) Risk of bias summary for included studies investigating the effect of dietary acetic acid supplementation vs
placebo/low-dose comparators on fasting glucose, lipid levels, and body composition in adults. Authors’judgments are shown for
each risk of bias item for all included trials, according to the Cochrane Risk-of-Bias tool.
33
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 17
5. Cani PD, Delzenne NM. The role of the gut microbiota in energy
metabolism and metabolic disease. Curr Pharm Des. 2009;15(13):
1546-1558.
6. Korner J, Aronne LJ. Pharmacological approaches to weight reduc-
tion: therapeutic targets. J Clin Endocrinol Metab. 2004;89(6):2616-
2621.
7. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a
systematic and clinical review. JAMA. 2014;311(1):74-86.
8. Greenway FL, Caruso MK. Safety of obesity drugs. Expert Opin Drug
Saf. 2005;4(6):1083-1095.
9. Petsiou EI, Mitrou PI, Raptis SA, Dimitriadis GD. Effect and mecha-
nisms of action of vinegar on glucose metabolism, lipid profile, and
body weight. Nutr Rev. 2014;72(10):651-661.
10. Hernández MAG, Canfora EE, Jocken JWE, Blaak EE. The short-chain
fatty acid acetate in body weight control and insulin sensitivity.
Nutrients. 2019;11(8):1943.
11. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud D-J,
Bakker BM. The role of short-chain fatty acids in the interplay be-
tween diet, gut microbiota, and host energy metabolism. J Lipid Res.
2013;54(9):2325-2340.
12. Keenan MJ, Zhou J, Hegsted M, et al. Role of resistant starch in
improving gut health, adiposity, and insulin resistance. Adv Nutr.
2015;6(2):198-205.
13. Bloemen JG, Venema K, van de Poll MC, Olde Damink SW,
Buurman WA, Dejong CH. Short chain fatty acids exchange across
the gut and liver in humans measured at surgery. Clin Nutr.
2009;28(6):657-661.
14. Stipanuk M, Caudell M. Biochemical, Physiological, and Molecular
Aspects of Human Nutrition. 3rd ed. Elsevier; 2012.
15. Lim J, Henry CJ, Haldar S. Vinegar as a functional ingredient to
improve postprandial glycemic control-human intervention findings
and molecular mechanisms. Mol Nutr Food Res. 2016;60(8):1837-
1849.
16. Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota meta-
bolic interactions. Science. 2012;336(6086):1262-1267.
17. Ali Z, Wang Z, Amir RM, et al. Potential uses of vinegar as a medicine
and related in vivo mechanisms. Int J Vitam Nutr Res. 2016;86(3-4):
127-151.
18. Budak NH, Aykin E, Seydim AC, Greene AK, Guzel-Seydim ZB.
Functional properties of vinegar. JFoodSci. 2014;79(5):R757-
R764.
19. Breidt F, McFeeters RF, Pérez-Díaz I, Lee C-H. Fermented vegeta-
bles. In: Doyle MP, Buchanan RL, eds. Food Microbiology: Funda-
mentals & Frontiers.4
th
ed. American Society of Microbiology;
2013.
20. Sarkola T, Iles MR, Kohlenberg-Mueller K, Eriksson CJ. Ethanol,
acetaldehyde, acetate, and lactate levels after alcohol intake in white
men and women: effect of 4-methylpyrazole. Alcohol Clin Exp Res.
2002;26(2):239-245.
21. Gill PA, van Zelm MC, Ffrench RA, Muir JG, Gibson PR. Successful
elevation of circulating acetate and propionate by dietary modula-
tion does not alter T-regulatory cell or cytokine profiles in healthy
humans: a pilot study. Eur J Nutr. 2020;59(6):2651-2661.
22. Yamashita H, Maruta H, Jozuka M, et al. Effects of acetate on lipid
metabolism in muscles and adipose tissues of type 2 diabetic Otsuka
Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem.
2009;73(3):570-576.
23. Gu X, Zhao HL, Sui Y, Guan J, Chan JC, Tong PC. White rice vinegar
improves pancreatic beta-cell function and fatty liver in
streptozotocin-induced diabetic rats. Acta Diabetol. 2012;49(3):185-
191.
24. 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.
25. Li X, Chen H, Guan Y, et al. Acetic acid activates the AMP-activated
protein kinase signaling pathway to regulate lipid metabolism in
bovine hepatocytes. PLoS One. 2013;8(7). 2013;e67880.
26. Beh BK, Mohamad NE, Yeap SK, et al. Anti-obesity and anti-
inflammatory effects of synthetic acetic acid vinegar and Nipa vin-
egar on high-fat-diet-induced obese mice. Sci Rep. 2017;7(1):6664.
27. 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.
28. Higgins JPT. Cochrane Handbook for Systematic Reviews of In-
terventions. Version 5.1.0. [Updated March 2011]. Accessed February
20, 2019, http://handbook.cochrane.org.
29. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items
for systematic reviews and meta-analyses: the PRISMA statement.
J Clin Epidemiol. 2009;62(10):1006-1012.
30. Covidence Systematic Review Software. Veritas Health Innovation;
2017.
31. Cheng LJ, Jiang Y, Wu VX, Wang W. A systematic review and meta-
analysis: vinegar consumption on glycaemic control in adults with
type 2 diabetes mellitus. J Adv Nurs. 2020;76(2):459-474.
32. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collabo-
ration’s tool for assessing risk of bias in randomised trials. BMJ.
2011;343.
33. Higgins JPT, Altman DG, Sterne JAC. Assessing risk of bias in included
studies. Chapter 8. In: Higgins JPT, Churchill R, Chandler J, Cumpston
MS, eds. Cochrane Handbook for Systematic Reviews of In-
terventions, version 5.2.0. Cochrane; 2017. Updated June 2017.
Accessed March 25, 2019. http://handbook.cochrane.org
34. RevMan. The Cochrane Collaboration; 2014.
35. Brockwell SE, Gordon IR. A comparison of statistical methods for
meta-analysis. Stat Med. 2001;20(6):825-840.
36. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-
analysis. Stat Med. 2002;21(11):1539-1558.
37. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis
detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.
38. Begg CB, Mazumdar M. Operating characteristics of a rank correla-
tion test for publication bias. Biometrics. 1994;50(4):1088-1101.
39. Macaskill P, Walter SD, Irwig L. A comparison of methods to detect
publication bias in meta-analysis. Stat Med. 2001;20(4):641-654.
40. Ali Z, Ma H, Wali A, Ayim I, Rashid MT, Younas S. A double-blinded,
randomized, placebo-controlled study evaluating the impact of dates
vinegar consumption on blood biochemical and hematological pa-
rameters in patients with type 2 diabetes. Trop J Pharm Res.
2018;17(2):2463-2469.
41. Ali Z, Ma H, Wali A, Ayim I, Sharif MN. Daily date vinegar con-
sumption improves hyperlipidemia,
b
-carotenoid and inflammatory
biomarkers in mildly hypercholesterolemic adults. J Herb Med.
2019;17-18:100265.
42. An SY, Lee MS, Jeon JY, et al. Beneficial effects of fresh and fermented
kimchi in prediabetic individuals. Ann Nutr Metab. 2013;63(1-2):
111-119.
43. Choi IH, Noh JS, Han J-S, Kim HJ, Han E-S, Song YO. Kimchi, a
fermented vegetable, improves serum lipid profiles in healthy
young adults: randomized clinical trial. J Med Food. 2013;16(3):
223-229.
44. Derakhshandeh-Rishehri S-M, Heidari-Beni M, Feizi A, Askari G-R,
Entezari M-H. Effect of honey vinegar syrup on blood sugar and lipid
profile in healthy subjects. Int J Prev Med. 2014;5(12):1608-1615.
45. 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 pa-
tients with type 2 diabetes and dyslipidemia: a randomized
controlled clinical trial. Clin Nutr ESPEN. 2019;33:132-138.
46. Johnston CS, Quagliano S, White S. Vinegar ingestion at mealtime
reduced fasting blood glucose concentrations in healthy adults at
risk for type 2 diabetes. J Funct Foods. 2013;5(4):2007-2011.
47. Johnston CS, White AM, Kent SM. Preliminary evidence that regular
vinegar ingestion favorably influences hemoglobin A1c values in
individuals with type 2 diabetes mellitus. Diabetes Res Clin Pract.
2009;84(2):e15-e17.
48. Kim EK, An S-Y, Lee M-S, et al. Fermented kimchi reduces body
weight and improves metabolic parameters in overweight and obese
patients. Nutr Res. 2011;31(6):436-443.
49. 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.
50. Mahmoodi M, Hosseini-Zijoud SM, Hassanshahi G, et al. The effect of
white vinegar on some blood biochemical factors in type 2 diabetic
patients. Glob J Hematol Endocrinol. 2013;1(1):50-54.
RESEARCH
18 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
51. Park JE, Kim JY, Kim J, et al. Pomegranate vinegar beverage reduces
visceral fat accumulation in association with AMPK activation in
overweight women: a double-blind, randomized, and placebo-
controlled trial. J Funct Foods. 2014;8:274-281.
52. Wang C-K, Fu HY, Chiang M. Cardiovascular disease prevention of
cranberry vinegar. Nutr Sci J. 2007;32(4):129-132.
53. Jasbi P, Baker O, Shi X, et al. Daily red wine vinegar ingestion for
eight weeks improves glucose homeostasis and affects the metab-
olome but does not reduce adiposity in adults. Food Funct.
2019;10(11):7343-7355.
54. Kausar S, Abbas MA, Ahmad H, et al. Effect of apple cider vinegar in
type 2 diabetic patients with poor glycemic control: a randomized
placebo controlled design. Int J Med Res Health Sci. 2019;8(2):149-159 .
55. 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):4.
56. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting
of randomized controlled trials: the consort statement. JAMA.
1996;276(8):637-639.
57. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated
guidelines for reporting parallel group randomised trials. BMJ.
2010;340:c332.
58. Shishehbor F, Mansoori A, Sarkaki AR, Jalali MT, LatifiSM. Apple cider
vinegar attenuates lipid profile in normal and diabetic rats. Pak J Biol
Sci. 2008;11(23):2634-2638.
59. Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T.
Acetic acid activates hepatic AMPK and reduces hyperglycemia in
diabetic KK-A(y) mice. Biochem Biophys Res Commun. 2006;344(2):
597-604.
60. Marques FZ, Nelson E, Chu PY, et al. High-fiber diet and acetate
supplementation change the gut microbiota and prevent the
development of hypertension and heart failure in hypertensive mice.
Circulation. 2017;135(10):964-977.
61. Santos HO, de Moraes WMAM, da Silva GAR, Prestes J, Schoenfeld BJ.
Vinegar (acetic acid) intake on glucose metabolism: a narrative re-
view. Clin Nutr ESPEN. 2019;32:1-7.
62. Lu ZX, Walker KZ, Muir JG, O’Dea K. Arabinoxylan fibre improves
metabolic control in people with type II diabetes. Eur J Clin Nutr.
2004;58:621.
63. Boll EV, Ekstrom LM, Courtin CM, et al. Effects of wheat bran extract
rich in arabinoxylan oligosaccharides and resistant starch on over-
night glucose tolerance and markers of gut fermentation in healthy
young adults. Eur J Nutr. 2016;55(4):1661-1670.
64. Kimura I, Ozawa K, Inoue D, et al. The gut microbiota suppresses
insulin-mediated fat accumulation via the short-chain fatty acid
receptor GPR43. Nat Commun. 2013;4:1829.
65. Johnston CS, Kim CM, Buller AJ. Vinegar improves insulin sensitivity
to a high-carbohydrate meal in subjects with insulin resistance or
type 2 diabetes. Diabetes Care. 2004;27(1):281-282.
66. Ostman E, Granfeldt Y, Persson L, Bjorck I. Vinegar supplementa-
tion lowers glucose and insulin responses and increases satiety
afterabreadmealinhealthysubjects.Eur J Clin Nutr. 2005;59(9):
983-988.
67. Freeland KR, Wolever TM. Acute effects of intravenous and rectal
acetate on glucagon-like peptide-1, peptide YY, ghrelin,
adiponectin and tumour necrosis factor-alpha. Br J Nutr.
2010;103(3):460-466.
68. Brown AJ, Goldsworthy SM, Barnes AA, et al. The Orphan G protein-
coupled receptors GPR41 and GPR43 are activated by propionate and
other short chain carboxylic acids. J Biol Chem. 2003;278(13):11312-
11319.
69. Ang Z, Ding JL. GPR41 and GPR43 in obesity and inflammation:
protective or causative? Front Immunol. 2016;7. 28-28.
70. Karra E, Chandarana K, Batterham RL. The role of peptide YY in
appetite regulation and obesity. J Physiol. 2009;587(1):19-25.
71. Barrera JG, Sandoval DA, D’Alessio DA, Seeley RJ. GLP-1 and energy
balance: an integrated model of short-term and long-term control.
Nat Rev Endocrinol. 2011;7(9):507-516.
72. Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by
dietary fibers alleviate type 2 diabetes. Science. 2018;359(6380):
1151-1156.
73. Sugiyama S, Fushimi T, Kishi M, et al. Bioavailability of acetate from
two vinegar supplements: capsule and drink. J Nutr Sci Vitaminol
(Tokyo). 2010;56(4):266-269.
74. Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid ki-
netics, and whole-body lipid balances in humans after acute alcohol
consumption. Am J Clin Nutr. 1999;70(5):928-936.
75. Hu J, Kyrou I, Tan BK, et al. Short-chain fatty acid acetate stimulates
adipogenesis and mitochondrial biogenesis via GPR43 in brown
adipocytes. Endocrinology. 2016;157(5):1881-1894.
76. Gill PA, van Zelm MC, Muir JG, Gibson PR. Review article: short chain
fatty acids as potential therapeutic agents in human gastrointestinal
and inflammatory disorders. Aliment Pharmacol Ther. 2018;48(1):15-
34.
77. Petersen KF, Impellizeri A, Cline GW, Shulman GI. The effects of
increased acetate turnover on glucose-induced insulin secretion in
lean and obese humans. J Clin Transl Sci. 2019;3(1):18-20.
78. Liu J, Zeng F-F, Liu Z-M, Zhang C-X, Ling W-h, Chen Y-M. Effects of
blood triglycerides on cardiovascular and all-cause mortality: a
systematic review and meta-analysis of 61 prospective studies. Lipid
Health Dis. 2013;12(1):159.
79. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a
cardiovascular risk factor. Am J Cardiol. 1998;81(4 Suppl 1):7B-12B.
80. Tayek CJ, Cherukuri L, Hamal S, Tayek JA. Importance of fasting blood
glucose goals in the management of type 2 diabetes mellitus: a re-
view of the literature and a critical appraisal. J Diab Metab Disord
Cont. 2018;5(4):113-117.
81. Aykın E, Budak N, Güzel-Seydim ZB. Bioactive components of mother
vinegar. J Am Coll Nutr. 2015;34(1):80-89.
82. Sáiz-Abajo MJ, González-Sáiz JM, Pizarro C. Multi-objective optimi-
sation strategy based on desirability functions used for chromato-
graphic separation and quantification of l-proline and organic acids
in vinegar. Anal Chim Acta. 2005;528(1):63-76.
83. Jung JY, Lee SH, Kim JM, et al. Metagenomic analysis of kimchi, a
traditional Korean fermented food. Appl Environ Microbiol.
2011;77(7):2264.
84. Natera R, Castro R, de Valme Garcia-Moreno M, Hernandez MJ,
Garcia-Barroso C. Chemometric studies of vinegars from different
raw materials and processes of production. J Agric Food Chem.
2003;51(11):3345-3351.
RESEARCH
-- 2020 Volume -Number -JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS 19
AUTHOR INFORMATION
D. S. Valdes is , Be Active Sleep and Eat (BASE) Facility, Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Australia.
D. So is , Department of Gastroenterology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, Victoria, Australia. P. A.
Gill is , Department of Gastroenterology, and , Department of Immunology and Pathology, Central Clinical School, Monash University and
Alfred Hospital, Melbourne, Victoria, Australia. N. J. Kellow is , Be Active Sleep and Eat (BASE) Facility, Department of Nutrition, Dietetics and
Food, Monash University, Notting Hill, Australia.
Address correspondence to: Nicole J. Kellow, Nicole Kellow, PhD, Monash University, Notting Hill, VIC, Australia. E-mail:
nicole.kellow@monash.edu
STATEMENT OF POTENTIAL CONFLICT OF INTEREST
No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT
This research did not receive any specific grant from funding agencies in the public, commercial or non-for-profit sectors.
ACKNOWLEDGEMENT
D. S. Valdes wishes to acknowledge Lorena Romero, Research & Training librarian at the Alfred Hospital for her assistance in the optimization of
the final systematic search strategy. (Permission has been obtained from Lorena Romero for her name to be acknowledged).
AUTHOR CONTRIBUTIONS
D. S. Valdes designed the review protocol, conducted the search, and drafted the manuscript. D. S. Valdes and D. So screened potentially eligible
studies, and extracted and analyzed the data. D. S. Valdes and N. J. Kellow conducted risk of bias assessment. D. So, P. A. Gill, and N. J. Kellow
drafted the manuscript, interpreted the data, and critically revised the manuscript for important intellectual content. All authors provided final
approval of the manuscript to be submitted.
RESEARCH
20 JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS -- 2020 Volume -Number -
Corrigendum
CORRIGENDUM
Corrigendum to: 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.
In the article “Effect of Dietary
Acetic Acid Supplementation on
Plasma Glucose, Lipid Profiles, and
Body Mass Index in Human Adults: A
Systematic Review and Meta-analysis”
in the May 2021 issue of the Journal of
the Academy of Nutrition and
Dietetics a data entry error was
recently identified in this systematic
review
1
, which has now been cor-
rected. The authors regret this error. In
addition, standard deviations extrac-
ted from an article
2
included in the
systematic review were published
incorrectly so the authors were con-
tacted and have subsequently pro-
vided the correct standard deviations.
An updated summary of results is
provided in Table 1. After the data