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Clinical Study
Vinegar Consumption Increases Insulin-Stimulated Glucose
Uptake by the Forearm Muscle in Humans with Type 2 Diabetes
Panayota Mitrou,1Eleni Petsiou,2Emilia Papakonstantinou,2
Eirini Maratou,1Vaia Lambadiari,2Panayiotis Dimitriadis,3Filio Spanoudi,2
Sotirios A. Raptis,1,2 and George Dimitriadis2
1Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and Its Complications (HNDC),
3 Ploutarchou Street, 10675 Athens, Greece
22nd Department of Internal Medicine and Research Institute, Athens University Medical School, Attikon University Hospital,
1 Rimini Street, 12462 Haidari, Greece
3Department of Water Resources and Environmental Engineering, School of Civil Engineering, NTUA, Heroon Polytechniou 5-9,
15780 Athens, Greece
Correspondence should be addressed to Panayota Mitrou; pmitrou@hndc.gr
Received December ; Accepted April
Academic Editor: Brunella Capaldo
Copyright © Panayota Mitrou et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Background and Aims. Vinegar has been shown to have a glucose-lowering eect in patients with glucose abnormalities. However,
the mechanisms of this eect are still obscure. e aim of this randomised, crossover study was to investigate the eect of vinegar on
glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal. Materials and Methods.
Eleven subjects with DM consumed vinegar or placebo (at random order on two separate days, a week apart), before a mixed
meal. Plasma glucose, insulin, triglycerides, nonesteried fatty acids (NEFA), and glycerol were measured preprandially and at –
min for min postprandially from the radial artery and from a forearm vein. Muscle blood ow was measured with strain-
gauge plethysmography. Glucose uptake was calculated as the arteriovenous dierence of glucose multiplied by blood ow. Results.
Vinegar compared to placebo () increased forearm glucose uptake (𝑝 = 0.0357), () decreased plasma glucose (𝑝 = 0.0279),
insulin (𝑝 = 0.0457), and triglycerides (𝑝 = 0.0439), and () did not change NEFA and glycerol. Conclusions.InDMvinegar
reduces postprandial hyperglycaemia, hyperinsulinaemia, and hypertriglyceridaemia without aecting lipolysis. Vinegar’s eect
on carbohydrate metabolism may be partly accounted for by an increase in glucose uptake, demonstrating an improvement in
insulin action in skeletal muscle. is trial is registered with Clinicaltrials.gov NCT.
1. Introduction
A mixture of vinegar and olive oil is a common salad dressing
used in the Mediterranean diet. e main constituent of
vinegar is acetic acid, which gives vinegar its characteristic
taste and smell. e consumption of vinegar with meals was
used as a folk medicine for the treatment of diabetes before
any pharmacologic glucose-lowering therapy [,]. Recent
studies indicate that vinegar improves insulin sensitivity
in healthy volunteers, as well as in subjects with diabetes
[–].
e mechanisms by which vinegar reduces glucose levels
are still unclear. Acetic acid has been shown to delay gastric
emptying in healthy subjects []andpatientswithtype
diabetes []; alternatively, acetic acid may inhibit disaccha-
ridase activity in the small intestine and suppress the enteral
carbohydrate absorption []. In addition, vinegar ingestion
at bedtime has been shown to decrease fasting glucose levels
in humans with type diabetes, suggesting an eect of acetic
acid on endogenous glucose production []. e mecha-
nisms of vinegar’s eect on peripheral tissues have been
studied in animals; these studies demonstrate that acetic acid
Hindawi Publishing Corporation
Journal of Diabetes Research
Volume 2015, Article ID 175204, 7 pages
http://dx.doi.org/10.1155/2015/175204
Journal of Diabetes Research
feeding reduces glycolysis and promotes glycogen synthesis,
probably by reducing xylulose -phosphate accumulation in
the liver and phosphofructokinase- activity in muscle [–
]. However, the eect of vinegar on glucose metabolism in
skeletalmusclehasnotbeenstudiedinhumanswithtype
diabetes.
In addition, previous studies indicate that acetate may
also decrease circulating lipid levels [–]andprotectfrom
lipidaccumulationinliverandskeletalmuscle[]; however,
these data are derived either from animal models or from a
few human studies with serious limitations.
eaimofthisstudywastoinvestigatetheeectsof
vinegaron()muscleglucoseuptakeandbloodowrates
and () circulating plasma glucose, insulin, and lipid levels,
in patients with type diabetes, using the arteriovenous
dierence technique across the forearm muscles.
2. Subjects and Methods
2.1. Subjects. A total of eleven nonsmoking volunteers with
type diabetes ( males, age 53 ± 4 years, BMI 25 ± 1,and
HbAc 6.8 ± 0.3%) participated in the study. e subjects
were newly diagnosed (according to the current criteria
for the diagnosis of type diabetes) without drug therapy
and free of diabetic complications or any other systematic
disease. eir diet and body weight were stable during the
last two months. All subjects were recreationally active,
without any specic training programme. e subjects were
instructed not to consume any acetic acid containing product
for two weeks prior to the study. e study was approved
by the hospital ethics committee, and subjects gave written
informed consent.
2.2. Experimental Protocol. All subjects arrived at the hospital
at h aer an overnight fast and had the radial artery
(A) and a contralateral antecubital vein (V) draining the
forearm muscles catheterized [,]. Half an hour aer
catheterisation, the subjects were assigned to consume vine-
gar ( mL vinegar containing % acetic acid and mL
water) or placebo ( mL water). e drinks were served at
random order on two separate days which were a week apart.
In each test, min aer the drink, the subjects consumed
a meal composed of bread, cheese, turkey ham, orange
juice, butter, and a cereal bar ( kcal; g carbohydrates,
gprotein,andgfat);themealwasconsumedsteadily
within min. Blood samples were withdrawn from both
sides preprandially and at – min intervals for min
aer meal for measurements of glucose (Yellow Springs
Instruments, Yellow Springs, OH) and insulin (RIA; Linco
Research, St. Charles, MO) and from the radial artery for
measurements of triglycerides and NEFA and glycerol (Roche
Diagnostics, Mannheim, Germany). A full blood count was
performed preprandially.
Blood ow (BF) was measured immediately before each
blood sample in the forearm with mercury strain-gauge
plethysmography (Hokanson, Bellevue, WA) in the same arm
as the forearm vein.
2.3. Calculations. Glucose plasma levels were converted to
whole blood by using fractional hematocrit [,]. Areas
undercurvewerecalculatedbythetrapezoidrulefromthe
startofthemealtomin(AUC
0–300). Glucose uptake
by muscle was calculated as the arteriovenous dierence of
glucose multiplied by the blood ow rates [,].
Results are presented as mean ±sem. Normality tests were
applied to each dependent variable; all variables studied were
normally distributed. Dierences between the AUCs of the
dependent variables were tested with paired Student’s 𝑡-test
(SPSS Inc., Chicago, IL, USA).
3. Results
Vinegar ingestion was well tolerated; no side-eects were
reported.
3.1. Glucose Metabolism
3.1.1. Arterial Levels of Glucose and Insulin. Fasting blood
glucoselevelsweresimilarbetweenthetwogroups.Inthe
patients who had consumed placebo, blood glucose levels
raised postprandially reaching a peak aer min, whereas
aer the consumption of vinegar postprandial glucose spikes
were decreased (Figure (a)). As a result, vinegar compared
to placebo reduced total blood glucose levels (AUC0–300 min
± versus 3005 ± 149mM ∗min, in vinegar and
placebo group, resp., 𝑝 = 0.0279).
Plasma insulin levels were similar between the two exper-
iments in the fasting state. However, vinegar consumption
decreased postprandial hyperinsulinaemia (AUC0–300 min
± versus ± mU/L ∗min, in vinegar and
placebo group, resp., 𝑝 = 0.0457)(Figure (b)).
3.1.2. Forearm Blood Flow. Forearm blood ow rates were
similar in the fasting state and remained not statisti-
cally dierent throughout the whole postprandial period
in both groups (AUC0–300 min ± versus 1100 ±
86mL/min/ mL tissue ∗mininvinegarandplacebo
group, resp.) (Figure (a)).
3.2. Muscle Glucose Metabolism. In the fasting state, glucose
uptake by the forearm muscles was similar in both groups.
Postprandially, muscle glucose uptake was increased in the
vinegar group compared to placebo (AUC0–300 min 765 ± 87
versus ± 𝜇mol/ mL tissue, in vinegar and placebo
group, resp., 𝑝 = 0.0357)(Figure (b)).
3.3. Lipid Metabolism. Fasting plasma triglyceride levels were
similar between the two groups. In the vinegar group post-
prandial hypertriglyceridemia was less evident, resulting in
decreased total plasma triglyceride levels (AUC0–300 min 371±
34 versus 409 ± 38nmol/L ∗min, in vinegar and placebo
group, resp., 𝑝 = 0.0439)(Figure (a)).
Fasting plasma NEFA and glycerol levels were not
dierent between the two groups. Postprandial plasma
NEFA (AUC0–300 min 46 ± 5 versus 49 ± 10nmol/L ∗min,
in vinegar and placebo group, resp.) and glycerol levels
Journal of Diabetes Research
6
8
10
12
14
16
−60 0 60 120 180 240 300
Time (min)
Arterial plasma glucose (mmol/L)
V−
V+
(a)
0
40
80
120
160
0 60 120 180 240 300
Time (min)
Arterial plasma insulin (𝜇U/mL)
−60
V−
V+
(b)
F : Arterial plasma glucose (𝑝 = 0.0279) (a) and insulin (𝑝 = 0.0457) (b) levels in subjects consuming vinegar (V+) or placebo (V−).
At 𝑡=0min, a mixed meal was given.
2.0
3.0
4.0
5.0
6.0
0 60 120 180 240 300
Time (min)
Muscle blood ow
(mL/min/100 mL tissue)
−60
V−
V+
(a)
0
1
2
3
4
5
6
0 60 120 180 240 300
Time (min)
Forearm glucose uptake
−60
(𝜇mol/min/mL tissue)
V−
V+
(b)
F : Forearm muscle glucose uptake (𝑝 = 0.0357) (a) and muscle blood ow (p = NS) (b) in subjects consuming vinegar (V+) or placebo
(V−). At 𝑡=0min, a mixed meal was given.
(AUC0–300 min 4± 0.4 versus 5±0.5nmol/L ∗min, in vinegar
and placebo group, resp.) were suppressed to the same extent
between groups (Figures (b) and (c)).
4. Discussion
e present study investigates the eects of vinegar on
circulating plasma glucose, insulin, and lipid levels, as well as
blood ow rates and glucose uptake by the forearm muscles,
in patients with type diabetes. For this purpose we have used
the arteriovenous dierence technique across the forearm
muscle, aer the ingestion of a mixed meal, in order to create
a metabolic environment which permits the interaction of
insulin and substrates to be investigated under physiological
conditions [,,,].Toourknowledge,thisistherst
report examining the eect of vinegar on glucose metabolism
intheskeletalmuscleinhumanswithtypediabetes.
In the present study, vinegar reduced postprandial hyper-
glycaemia.isissupportedbypreviousreportsshowing
that vinegar supplementation reduces postprandial blood
glucoselevelsinhealthysubjects[–], as well as in subjects
with insulin resistance and type diabetes [,]. It is
also in accordance with a preliminary study reporting that
regular vinegar ingestion reduces haemoglobin Ac values
in patients with type diabetes []. However, our results
are not in agreement with a previous report showing that
vinegar ingestion before an oral glucose load did not improve
oral glucose tolerance in patients with type diabetes [].
ese discrepancies could be explained, at least in part,
by dierences in the form of acetic acid, as well as the
kind of the test meal following acetic acid ingestion. As
shown previously, acetic acid reduced postprandial glucose
values when it was administered in the form of vinegar, but
not in the form of sodium acetate []. In addition, the
glucose-lowering eect of vinegar was evident when vinegar
Journal of Diabetes Research
800
1000
1200
1400
1600
1800
0 60 120 180 240 300
Time (min)
Plasma triglycerides (𝜇mol/L)
−60
V−
V+
(a)
50
100
150
200
250
300
350
0 60 120 180 240 300
Time (min)
−60
Plasma NEFA (𝜇mol/L)
V−
V+
(b)
5
10
15
20
25
0 60 120 180 240 300
Time (min)
−60
Plasma glycerol (𝜇mol/L)
V−
V+
(c)
F : Arterial plasma triglycerides (𝑝 = 0.0439) (a), NEFA (p = NS) (b), and glycerol (p = NS) (c) levels in subjects consuming vinegar
(V+) or placebo (V−). At 𝑡=0min, a mixed meal was given.
was ingested with complex carbohydrates, but not with
monosaccharides [,]. Moreover, a previous study showed
that vinegar reduced postprandial glycaemia in patients with
typediabeteswhenaddedtoahigh,butnottoalow,
glycaemic index meal [].
Glucose regulation depends mainly on insulin secretion
bythepancreaticbeta-cellsandinsulinactiononperipheral
tissues. In our study, insulin levels were decreased aer
the consumption of vinegar, conrming previous reports
[,], suggesting that the hypoglycemic eect of vinegar
may be mediated through an eect on insulin action in the
peripheral tissues. Skeletal muscle is considered as the most
important tissue for insulin-stimulated glucose uptake [].
Inourstudyvinegaringestionenhancedglucosedisposal,
suggesting an improvement in insulin action in skeletal
muscle. It is well known that insulin aects vascular endothe-
lium and increases muscle and adipose tissue blood ow
by increasing vasodilation and capillary recruitment [–
]. is eect is considered as an important component of
insulin’s stimulation of glucose uptake; impairment of this
mechanism in insulin-sensitive tissues may partly account
for insulin resistance in obesity and type diabetes [,
]. Previous studies in nondiabetic humans suggest that
vinegar ingestion may enhance ow-mediated vasodilation
through endothelial nitric oxide synthase phosphorylation
[]. In addition, our previously published data on the eects
of vinegar on muscle blood ow in subjects with impaired
glucose tolerance have shown that vinegar ingestion before
amixedmealresultsinanenhancementofmuscleblood
ow rates aer the meal, although postprandial insulin levels
were decreased compared to their respective values in the
group consuming placebo []. However, in our study vinegar
ingestion did not alter muscle blood ow rates, suggesting
that the increase in glucose disposal aer meal ingestion may
not be attributed to a direct eect of vinegar on blood ow
in subjects with type diabetes. A possible explanation for
this discrepancy between individuals with impaired glucose
tolerance and patients with type diabetes could be that in
the early stages of glucose intolerance the defect of blood ow
may be reversible; however in overt type diabetes the defect
in ow-mediated vasodilatation may be already established
and cannot be reversed by vinegar ingestion.
Journal of Diabetes Research
e eect of vinegar in the intracellular pathways of
glucosemetabolisminskeletalmusclehasbeenpreviously
examined in animal studies. In rats, acetic acid has been
shown to enhance glycogen repletion, attributed to accu-
mulation of glucose -phosphate due to suppression of
glycolysis [–]. e same eect has been reported in
horses aer exercise. In these studies acetate supplementation
enhanced the rate of muscle glycogen resynthesis during the
rst hours following the exercise period compared with the
control treatment []. Although the intracellular pathways
of glucose metabolism were not investigated in our study,
these in vitro studies suggest that the increase in glucose
uptake by the skeletal muscle following vinegar ingestion
could be explained by increased rates of glycogen synthesis.
In our study, vinegar ingestion decreased postprandial
hypertriglyceridaemia, without aecting NEFA and glycerol;
toourknowledge,thisistherststudyinvestigatingthe
acute eects of vinegar on lipid metabolism in subjects with
type diabetes. e eect of vinegar on lipid metabolism
has been investigated in several studies showing that chronic
administration of acetic acid reduces serum and hepatic
triglyceride levels [,,] in metabolically healthy animals.
In addition, chronically administered acetate treatment in
obese [] and/or type diabetic []ratshasbeenshownto
result in a reduction of plasma triglyceride levels. In contrast,
triglyceride levels were not aected by acute administration
of mL vinegar added to a hypercholesterolaemic diet in
rabbits []. On the other hand, information on humans
is limited to a few studies examining the chronic eect of
vinegar with conicting results. In these studies – mL
vinegar intake for – weeks resulted in a decrease of
serumtriglyceridelevelsinsubjectswithobesity[]or
hyperlipidaemia []. However, there was no eect of vinegar
intake in a prospective randomized, double blind, placebo-
controlled clinical study conducted in nondiabetic sub-
jects consuming mL apple vinegar for weeks []. e
results of this study should however be considered with
caution since this study had several limitations; the most
important is the mixed group of subjects (one-third of the
participants were on statin and/or sh oil treatment).
Previous animal studies suggest that the eect of vinegar
ontriglyceridelevelscouldbeattributedtotheinhibition
of hepatic lipogenesis and increase of fatty acid oxidation
[,]. However, this mechanism could not explain the
results of the present study, since vinegar ingestion had no
acute eect on plasma levels of NEFA and glycerol. As a result,
although chronic administration of vinegar could have an
impact on fatty acid metabolism [,] our study showed
that the acute administration of vinegar in subjects with type
diabetes does not aect lipolysis. A possible explanation
of these ndings could be that the acute intake of vinegar
increases insulin sensitivity of the adipose tissue, increasing
the lipoprotein lipase activity and the postprandial clearance
of triglycerides [,], with no eect on hormone-sensitive
lipase, which regulates lipolysis.
Although the arteriovenous dierence technique has
allowedinsightsintotheglucoseuxesacrosstheforearm
muscles, some limitations should be considered when inter-
preting the results. First, the number of participants was
relatively small. is was mainly due to the invasive nature
of the technique and the need for repeating the experiment
aer one week. However, due to the crossover design of
the study, our data were sucient for reaching statistical
signicance. Moreover, another limitation of our study was
that the patients had mild diabetes (HbAc: . ±.%). is
was due to the fact that we aimed to see the eect of vinegar
in patients with newly diagnosed diabetes, without diabetic
complications and without taking any medication therapy
that could aect glucose or lipid metabolism. Further studies
are needed to investigate the eect of vinegar on glucose
metabolism in patients with more severe type diabetes, as
well as in those taking various treatments.
In summary, our study showed that, in type diabetes,
vinegar reduces postprandial hyperglycaemia, hyperinsuli-
naemia, and hypertriglyceridaemia without aecting lipoly-
sis. As a result, vinegar’s eect on carbohydrate metabolism
maybeaccountedfor,atleastinpart,byanincrease
in insulin-stimulated glucose uptake, demonstrating an
improvement in insulin action in the skeletal muscles. How-
ever, further studies are required to examine the long-term
eects of vinegar in type diabetes.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
Acknowledgments
e authors are grateful to E. Pappas and I. Kosmopoulou
for technical support and V. Frangaki, RN, for help with
experiments.
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