Content uploaded by Hengye Chen
Author content
All content in this area was uploaded by Hengye Chen on Dec 29, 2017
Content may be subject to copyright.
Vinegar Functions on Health: Constituents,
Sources, and Formation Mechanisms
Hengye Chen, Tao Chen, Paolo Giudici, and Fusheng Chen
Abstract: Vinegars are one of only a few acidic condiments throughout the world. Vinegars can mainly be considered
grain vinegars and fruit vinegars, according to the raw materials used. Both grain vinegars and fruit vinegars, which
are fermented by traditional methods, possess a variety of physiological functions, such as antibacteria, anti-infection,
antioxidation, blood glucose control, lipid metabolism regulation, weight loss, and anticancer activities. The antibacteria
and anti-infection abilities of vinegars are mainly due to the presence of organic acids, polyphenols, and melanoidins.
The polyphenols and melanoidins also provide the antioxidant abilities of vinegars, which are produced from the raw
materials and fermentation processes, respectively. The blood glucose control, lipid metabolism regulation, and weight
loss capabilities from vinegars are mainly due to acetic acid. Besides caffeoylsophorose (inhibits disaccharidase) and
ligustrazine (improves blood circulation), other functional ingredients present in vinegars provide certain health benefits
as well. Regarding anticancer activities, several grain vinegars strongly inhibit the growth of some cancer cells in vivo or
in vitro, but related functional ingredients remain largely unknown, except tryptophol in Japanese black soybean vinegar.
Considering the discovering of various functional ingredients and clarifying their mechanisms, some vinegars could be
functional foods or even medicines, depending on a number of proofs that demonstrate these constituents can cure
chronic diseases such as diabetes or cardiovascular problems.
Keywords: vinegar, functional properties, functional ingredients, blood glucose control, lipid metabolism regulation,
anticancer
Introduction
Vinegars are one of only a few acidic condiments throughout
the world. Based on their raw materials, vinegars can mainly be
considered grain vinegars, which contain sorghum, rice, wheat, or
other grains as the raw materials, or fruit vinegars, which are based
on fruits such as grapes or apples as the raw materials. In addition,
vinegars can also be fermented from sugar and alcohol. Shanxi
aged vinegar, Zhenjiang aromatic vinegar, Sichuan Baoning bran
vinegar, and Fujian Yongchun Monascus vinegar, which are the
4 major traditional vinegars in China, are common grain vine-
gars in addition to Kurosu, a Japanese vinegar. In contrast, Italian
balsamic vinegar, Spanish Sherry vinegar, and American apple
vinegar are fruit vinegars (Solieri and Giudici 2009). Regardless
of the raw materials, vinegars are known to have several physio-
logical functions, especially those made by traditional techniques
(Budak and others 2014).
In approximately 400 BC, the ancient Greek Hippocrates began
to use fruit vinegars to treat wound inflammations, cough, ulcers,
MS 20160988 Submitted 21/6/2016, Accepted 25/8/2016. Authors H. Chen,
T. Chen, and F. Chen are with Key Laboratory of Environment Correlative Di-
etology and College of Food Science and Technology, Huazhong Agricultural Uni.,
Wuhan 430070, Hubei Province, People’s Republic of China. Author P. Giudici
are with Dept. of Life Sciences, Uni. of Modena and Reggio Emilia, Via Amen-
dola, 2, 42122 Reggio Emilia, Italy. Direct inquiries to author F. Chen (E-mail:
chenfs@mail.hzau.edu.cn).
and infectious diseases. The most ancient prescriptions displayed in
the Chinese Book Fifty-Two Diseases (300 BC) include 17 remedies
based on the use of grain vinegars to treat burns, hernias, cellulitis,
and psoriasis. Throughout all of the dynasties, subsequent Chinese
medical books also described many prescriptions that contained
grain vinegars (Xu and others 2003). Since the 18th century, many
records have recommended fruit vinegars to treat laryngitis, fever,
swelling, stomachache, and the rash from poison ivy exposure in
America (Budak and others 2014). Recent research studies have
indicated that vinegars possess antibacteria, anti-infection, antioxi-
dation, blood glucose control, lipid metabolism regulation, weight
loss, and anticancer properties (Budak and others 2014; Petsiou
and others 2014). The functional properties of vinegars have been
reviewed in several papers (Budak and others 2014; Petsiou and
others 2014; Pazuch and others 2015), but these reports mainly
focused on fruit vinegars and did not discuss functional ingredients
other than acetic acid. The present review summarizes the func-
tional properties of grain vinegars and fruit vinegars and compares
the functional ingredients, sources, and formation mechanisms of
grain and fruit vinegars.
Functional Properties of Vinegars
Many active functions of vinegars have been proven and re-
ported. In this section, the main functional properties of vinegars,
including antibacteria, anti-infection, antioxidation, blood glucose
control, lipid metabolism regulation, weight loss, anticancer, and
C2016 Institute of Food Technologists®
doi: 10.1111/1541-4337.12228 Vol. 00, 2016 rComprehensive Reviews in Food Science and Food Safety 1
Vinegar functions on health . . .
so on, will be reviewed, and the relative activities of grain and fruit
vinegars will be compared.
Antibacteria and anti-infection
Prior to the work of Pasteur and Koch on bacteria in the
19 century, vinegars were often employed in antibacterial and
anti-infection applications. In approximately 400 BC, the an-
cient Greek medical expert Hippocrates used fruit vinegars
to heal wounds, inflammations, coughs, and infections (Bu-
dak and others 2014). The Chinese medical book Compendium
of Materia Medica, which was authored in the Ming dynasty
(16 century), also shows records of the use of grain vine-
gars for Ascaris infection treatment, birth room disinfection,
meat preservation, and others (Xu and others 2003). Mod-
ern research studies (Table 1) have shown that fruit vinegars
containing 0.1% acetic acid effectively inhibit the growth of
food-borne pathogens in vitro, including those by Escherichia
coli O157:H7, Salmonella enteritidis, S. typhimurium, Vibrio para-
haemolyticus, Staphylococcus aureus, Aeromonas hydrophila, and Bacillus
cereus (Entani and others 1998). In addition, by soaking in either
grain or fruit vinegars for a short time, pathogenic bacteria were
successfully eradicated from vegetables (Sengun and Karapinar
2004; Chang and Fang 2007). Grain vinegars can effectively de-
stroy respiratory pathogens such as Micrococcus catarrhalis, Staphylo-
coccus albus, Diplococcus pneumonia, and Alpha streptococcus,whereas
apple vinegar strongly inhibits the growth of pathogenic bacte-
ria such as Staphylococcus epidermidis, Pseudomonas aeruginosa, Proteus
mirabilis, and Klebsiella pneumoniae (Hindi 2013). Moreover, irri-
gation of the ear canal with diluted vinegar has positive effects
on otitis and myringitis (Aminifarshidmehr 1996; Jung and others
2002).
Antioxidative effects
Vinegars are fermented products, mainly, of grains or fruits, and
contain large amounts of antioxidants (Table 1). In vitro stud-
ies have shown that the antioxidant capacities of Shanxi aged
vinegar (unpublished) and Italian balsamic vinegar (Tagliazucchi
and others 2007; Bertelli and others 2015) were equal to those
of 0.1% and 0.2% vitamin C solutions, respectively. Animal and
cell experiments have also indicated that both grain vinegars and
fruit vinegars can improve antioxidant capacities and reduce ox-
idative damage in vivo (Nishidai and others 2000; Xu and others
2005; Schaefer and others 2006; Tagliazucchi and others 2007;
Verzelloni and others 2007; Iizuka and others 2010; Verzelloni
and others 2010; Bertelli and others 2015; Liu and Yang
2015).
Blood glucose control
The effect of vinegar on blood glucose levels was first reported
by Ebihara and Nakajima in 1988, who found that 2% of acetic acid
in diet significantly reduced the blood glucose concentration of
rats after starch intake (Ebihara and Nakajima 1988). Subsequently,
a large number of human dietary studies also found that the intake
of fruit vinegars significantly reduced blood glucose levels after
the intake of starchy foods (specific dose effects were observed)
(Table 1) (Ebihara and Nakajima 1988; Johnston and Buller 2005;
Leeman and others 2005; Ostman and others 2005; Johnston and
others 2010; Mitrou and others 2010); however, monosaccharide-
induced blood glucose levels remained unchanged (Johnston and
others 2010). Moreover, grape vinegars neutralized by alkali or
consumed 5 h before a meal did not affect the postprandial blood
glucose concentration and insulin response, indicating that vinegar
plays a role in food digestion, which may be related to its acidity
(Brighenti and others 1995). In diets with high-glycemic indices,
apple vinegars significantly reduce the postprandial blood glucose
concentration and insulin response and increase satiety. However,
in low-glycemic diets, vinegars can only reduce the postprandial
insulin response and do not significantly influence the blood glu-
cose concentration, which may be due to the fact that a lower
blood glucose level cannot be achieved by the addition of vine-
gar after the consumption of a diet with a low-glycemic index
(Johnston and Buller 2005).
Compared to healthy people, the intake of apple vinegar also
increases the insulin sensitivity of patients with type 2 diabetes
(Ebihara and Nakajima 1988), and the intake of apple vinegar
at bedtime can help patients with type 2 diabetes to control
their fasting blood glucose concentration and prevent “diabetes
mellitus dawn phenomenon” in the next morning (White and
Johnston 2007). In a 12-week experiment, the dietary intake
of 1.4 g of acetic acid (2 meals per day) significantly reduced
the level of glycated hemoglobin (0.16%) in patients with type
2 diabetes (Johnston and others 2009). The consumption of ap-
ple vinegar over an extended period of time (99 – 110 d) can
also improve the insulin resistance of patients with polycystic
ovary syndrome and improve ovulation function (Wu and oth-
ers 2013). Although studies on the use of vinegars to control
blood glucose levels primarily focused on fruit vinegars, the long-
term intake of grain vinegars may also have a positive effect on
the blood glucose levels of humans, because acetic acid is able
to reduce the postprandial blood glucose concentration (Ebihara
and Nakajima 1988; Ostman and others 2005). Moreover, grain
vinegars have been shown to lower the blood glucose concentra-
tion of mice with diabetes (Ma and others 2010; Gu and others
2012).
Lipid metabolism regulation
Compared to investigations on the effects of vinegars on blood
glucose contents, studies on the regulation of blood lipid levels
were performed later and were primarily concentrated on ani-
mal experiments (Table 1). Many animal experiments have shown
that the long-term consumption of a specific amount of acetic
acid (Fushimi and others 2006), grain vinegars (Fan and others
2009; Li and others 2009; Liu and others 2015; Liu and Yang
2015), and fruit vinegars (Moon and Cha 2008; Setorki and oth-
ers 2010; Soltan and Shehata 2012) can significantly reduce the
concentration of total cholesterol, triglycerides, and low-density
lipoprotein (LDL) cholesterol and increase the concentration of
high-density lipoprotein (HDL) cholesterol. Moreover, the reg-
ulation of lipid metabolism by vinegars was also observed in
mice with type 2 diabetes and obese mice (Shishehbor and oth-
ers 2008; Kondo and others 2009a; De Dios Lozano and others
2012; Soltan and Shehata 2012; Liu and Yang 2015). Exper iments
on humans (8 wk) have revealed that the consumption of 30 mL
apple vinegar 2 times per day can significantly reduce total choles-
terol, triglycerides, and LDL levels of patients with hyperlipidemia
and increase the content of HDL in a nonsignificant manner
(Beheshti and others 2012). In another study on the effects of vine-
gar on lipids, triglyceride levels significantly decreased in obese
people consuming 15 mL apple vinegar every day (Kondo and
others 2009b). Although reports on the regulation of human lipid
metabolism due to grain vinegar consumption have not been pub-
lished, the long-term intake of grain vinegars may have positive
effects, according to previous animal experiments (Fan and others
2Comprehensive Reviews in Food Science and Food Safety rVol.00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
Table 1–Functional properties of vinegars.
Vinegar type Function Country Subjects Results Reference
Spirit vinegar Antibacteria Japan Food-borne pathogenic
bacteria
The growth of all strains evaluated was inhibited with a 0.1%
concentration of acetic acid in the vinegar.
Entani and others (1998)
Rice vinegar Antibacteria China E. coli O157:H7 Treatment of inoculated lettuce (107CFU/g bacteria) with vinegar
(5% acetic acid) for 5 min would reduce 3 logs population at 25 °C.
Chang and Fang (2007)
Grape vinegar Antibacteria Turkey Salmonella typhimurium Treatment of carrot samples with vinegar (4.03% acetic acid) for
different exposure times (0, 15, 30 and 60 min) caused significant
reductions ranging between 1.57 and 3.58 log CFU/g.
Sengun and Karapinar (2004)
Acetic acid solution Anti-infection Kuwait 96 patients with chronic
suppurative otitis media
The patients received ear irrigation with 2% acetic acid solution three
times per week (3 weeks, followed for up to 3 years).
55 patients had resolution of their original otorrhen, whereas
19 patients developed healed ear drum perforation. 14 patients
(15%) showed recurrence and
8 of them had no response to the treatment.
Aminifarshidmehr (1996)
Fermented vinegar Anti-infection Korea 15 patients with chronic
granular myringitis
The patients were treated with irrigation of the external canal with
dilute vinegar solution (pH =2.43) twice to four times per day. All
patients had resolution of their original otorrhoea within three weeks.
Jung and others (2002)
Shanxi aged vinegar Antioxidation China Hyperlipidemic mouse Fed with a diet with 1% freeze-dried powder of Shanxi aged vinegar for
35 d resulted in a significant increase of antioxidation ability in
mouse.
Liu and Yang (2015)
Shanxi aged vinegar Antioxidation China In vitro Reducing capacity: 98.94 ±1.58 mg Vc/100 mL Antiradical activity:
124.89 ±3.37 mg Vc/100 mL
Unpublished
Zhenjiang aromatic
vinegar
Antioxidation China Ageing accelerating mice Instilled with 1.2 g/kg·d vinegar for 35 d resulted in a significant
increase of antioxidation ability in mouse.
Xu and others (2005)
Kurosu Antioxidation Japan Mice The ethyl acetate extract of Kurosu significantly suppressed the 12-O-
tetradecanoylphorbol-13-acetate induced myeloperoxidase activity
and H2O2generation in mouse.
Nishidai and others (2000)
Traditional balsamic
vinegar
Antioxidation Italy In vitro Reducing capacity: 218.85 ±6.86 mg Vc/100 mL Antiradical activity:
298.10 ±6.25 mg Vc/100 mL
Tagliazucchi and others (2007)
Traditional balsamic
vinegar
Antioxidation Italy In vitro Reducing capacity: 27.12 ±11.1 μM Tes/mL Antiradical activity:
33.52 ±19.3 μM Tes/mL
Bertelli and others (2015)
Traditional balsamic
vinegar
Antioxidation Italy Simulated gastric The vinegar melanoidins (4.5 mg/mL) significantly inhibited the lipid
peroxidation during simulated gastric digestion of meat.
Verzelloni and others (2010)
Balsamic vinegar Antioxidation Japan Macrophage:THP-1 Balsamic vinegar (0.01%) significantly inhibited the low density
lipoprotein (LDL) oxidation and lipid accumulation in macrophages
Iizuka and others (2010)
Red wine vinegar Antioxidation Italy In vitro Reducing capacity: 48.18 ±2.00 mg Vc/100 mL Antiradical activity:
85.40 ±1.73 mg Vc/100 mL
Verzelloni and others (2007)
White vinegar Blood glucose control Sweden 12 healthy volunteers Supplementation of a meal with vinegar (18 g) reduced postprandial
responses of blood glucose and insulin and increased the subjective
rating of satiety.
Ostman and others (2005)
Bitter buckwheat
vinegar
Blood glucose control China Diabetic rats Oral intake of vinegar (2 mL/kg·d) for 4 weeks reduced about 17%
blood glucose in rats.
Ma and others (2010)
Rice vinegar Blood glucose control China Diabetic rats Oral intake of vinegar (2 mL/kg·d) for 30 d improved fasting
hyperglycemia and body weight loss through attenuating insulin
deficiency, pancreatic beta-cell deficit, and hepatic glycogen
depletion in rats.
Gu and others (2012)
Apple vinegar Blood glucose control America 11 patients with type 2
diabetes
Vinegar ingestion (30 mL) at bedtime moderates waking glucose
concentrations in adults with well-controlled type 2 diabetes.
White and Johnston (2007)
Apple vinegar Blood glucose control America 27 patients with type 2
diabetes
Oral intake of vinegar (30 mL/d) for 4 weeks significantly reduced
hemoglobin A1c values in individuals with type 2 diabetes mellitus.
Johnston and others (2009)
Apple vinegar Blood glucose control America 8 healthy volunteers Supplementation of a meal with vinegar (10 g) reduced about 20%
postprandial responses of blood glucose.
Johnston and others (2010)
Apple vinegar Blood glucose control Japan 7 patients with polycystic
ovary syndrome
Oral intake of vinegar (15 g/d) for 90 - 110 d improved insulin
sensitivity in individuals with polycystic ovary syndrome.
Wu and others (2013)
(Continued)
C2016 Institute of Food Technologists®Vol. 00, 2016 rComprehensive Reviews in Food Science and Food Safety 3
Vinegar functions on health . . .
Table 1–Continued.
Vinegar type Function Country Subjects Results Reference
Vinegar Blood glucose control Greece 10 patients with type 1
diabetes
Supplementation of a meal with vinegar (30 mL) reduced about 20%
postprandial responses of blood glucose.
Mitrou and others (2010)
Acetic acid solution lipid metabolism
regulation
Japan Human umbilical vein
endothelial cell
Vinegar intake enhances flow-mediated vasodilatation via upregulation
of endothelial nitric oxide synthase activity.
Sakakibara and others (2010)
Shanxi aged vinegar Lipid metabolism
regulation
China Hyperlipidemic mice Fed with a diet with 1% freeze-dried powder of vinegar for 35 d resulted
in a significant reduction of triglyceride, total cholesterol and LDL in
mouse.
Liu and Yang (2015)
Sorghum vinegar Lipid metabolism
regulation
China Rats Fed with a diet with extract of vinegar (100 mg/kg) protected the rats
against thrombotic death induced by collagen and epinephrine.
Fan and others (2009)
Grape vinegar Lipid metabolism
regulation
Iran Rabbits with high cholesterol
diet
Oral intake of 10 mL vinegar significantly reduced LDL-cholesterol,
oxidized-LDL malondialdehyde and total cholesterol in rabbits after
3hours.
Setorki and others (2010)
Grape vinegar Lipid metabolism
regulation
Egypt Diabetic rats Fed with a diet with 15% vinegar for 6 weeks significantly reduced
LDL-cholesterol and total cholesterol in rats.
Soltan and Shehata (2012)
Apple vinegar Lipid metabolism
regulation
Iran 19 patients with
hyperlipidemia
Oral intake of vinegar (30 mL/d, twice) for 8 weeks significantly
reduced triglyceride, total cholesterol and LDL in individuals with
hyperlipidemia.
Beheshti and others (2012)
Persimmon vinegar Lipid metabolism
regulation
Korea Mouse with high lipid diet Oral intake of vinegar (2 mL/kg·d) for 16 weeks significantly reduced
triglyceride and total cholesterol in mouse.
Moon and Cha (2008)
Acetic acid solution Weight loss Japan Obese mice Fed with 0.3 or 1.5% acetic acid solution for 6 weeks significantly
inhibited the accumulation of body fat and hepatic lipids without
changing food consumption or skeletal muscle weight.
Kondo and others (2009a)
Corn vinegar Weight loss China Obese mice Oral intake of vinegar (0.3 mL/d) for 30 d significantly reduced body
weight, fat coefficient, triglyceride and total cholesterol in mouse.
Li and others (2009)
Purple sweet potato
vinegar
Weight loss China Obese mice Oral intake of vinegar (10 mL/ kg·d) for 30 d significantly reduced body
weight, fat coefficient, LDL, triglyceride and total cholesterol in
mouse.
Liu and others (2015)
Apple vinegar Weight loss Japan 150 obese Japanese Oral intake of vinegar (15 mL/d) for 12 weeks significantly reduced
body weight, body fat mass and serum triglyceride levels in subjects.
Kondo and others (2009b)
Apple vinegar Weight loss Mexico Rats with high-caloric diets Oral intake of vinegar (0.8 mL/ kg·d) for 4 weeks significantly reduced
body weight, fat coefficient, LDL, triglyceride and total cholesterol in
rats.
De Dios Lozano and others
(2012)
Mulberry vinegar Weight loss China Obese mice Oral intake of vinegar (0.1 mL/d) for 30 d significantly reduced body
weight, fat coefficient, triglyceride and total cholesterol in mouse.
Wei and others (2005)
Hawthorn Vinegar Weight loss Turkey 37 Obese patients with
cardiovascular disease
Oral intake of vinegar (40 mL/d) for 4 weeks significantly reduced body
weight, body fat mass and serum triglyceride levels in subjects.
Kadas and others 2014
Shanxi aged vinegar Anticancer China Cancer cells (A549, Hep-G2,
MDA-MDB-231, Hela)
Ethyl acetate extract of vinegar (0.01%) significantly inhibited the
proliferation of cancer cells in vitro.
Chen and Gullo (2015)
Kurosu Anticancer Japan Rats with colon cancer Fed with water containing 0.05% ethyl acetate extract of Kurosu for
35 weeks significantly inhibited azoxymethane-induced colon
carcinogenesis in rats.
Shimoji and others (2004)
Kurosu Anticancer Japan Cancer cell (Caco-2, A549,
MCF-7, 5637, LNCaP)
Ethyl acetate extract of vinegar (0.025%) significantly inhibited the
proliferation of cancer cells in vitro.
Nanda and others (2004)
Black soybeans
vinegar
Anticancer Japan Leukemia U937 cells Ethyl acetate extract of vinegar (10 mg/mL) significantly inhibited the
proliferation of cancer cells in vitro.
Inagaki and others (2007)
Postdistillation slurry
vinegar
Anticancer Japan Mice with Sarcoma 180 and
Colon 38 tumor cells
Fed with a diet with 0.5% vinegar for 72 d significantly decreased the
sizes of tumors and prolonged life spans of mouse.
Seki and others (2004)
Sugarcane vinegar Anticancer Japan Leukemia cells: HL-60, THP-1,
Molt-4, U-937, K-562
Fraction eluted by 40% methanol from vinegar significantly inhibited
the proliferation of leukemia cells in vitro.
Mimura and others (2004)
Zhenjiang Aromatic
Vinegar
Antifatigue China Mouse Fed with a diet with vinegar (300 mg/kg·d) for 28 d significantly
improved antifatigue abilities of mouse.
Lu and Zhou (2002)
Mulberry vinegar Antifatigue China Mouse Fed with a diet with vinegar (0.2 mL/d) for 20 d significantly improved
antifatigue abilities of mouse.
Zhang and others (2007)
Grain vinegar Preventing
osteoporosis
Japan Ovariectomized rats Fed with a diet with 0.4% vinegar for 32 d significantly increased
intestinal absorption of calcium in rats.
Kishi and others (1999)
4Comprehensive Reviews in Food Science and Food Safety rVol.00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
2009; Li and others 2009, Liu and others 2015, Liu and Yang
2015).
Weight loss
Because vinegar alters the regulation of lipids, the long-term
intake of vinegars should also have an effect on weight loss
(Table 1). Obese animal model experiments have proven that the
long-term consumption of a specific amount of acetic acid (Kondo
and others 2009a), grain vinegars (Li and others 2009; Liu and oth-
ers 2015), or fruit vinegars (Wei and others 2005; De Dios Lozano
and others 2012) can significantly reduce the body weight, lipid
content, and total cholesterol and triglyceride contents of animals.
Human experiments have proven that the long-term intake of
fruit vinegars can also significantly reduce the body weight, body
mass index, and total cholesterol and triglyceride levels of healthy
people with obesity (Kondo and others 2009b) and obese people
with high blood pressure (Kadas and others 2014). Although the
effects of grain vinegars on human weight loss have not yet been
researched, previous animal experiments (Fan and others 2009; Li
and others 2009; Liu and others 2015; Liu and Yang 2015) suggest
that the long-term intake of grain vinegars may help weight loss
in obese people.
Anticancer
Until now, only a few studies on the anticancer activities of
vinegars have been published, most of which focused on grain
vinegars (Table 1). Cell-based experiments indicated that the ethyl
acetate extracts of Shanxi aged vinegar and Japanese black vinegar
significantly inhibited the proliferation of many types of cancer
cells in vitro, but the corresponding active ingredients have not
been identified (Nanda and others 2004; Seki and others 2004;
Baba and others 2013; Chen and Gullo 2015). Meanwhile, the
ethyl acetate extracts of Japanese black vinegar increased the ex-
pression of p21 genes, allowing human colon cancer cells in the
G0/G1 phase to undergo apoptosis, and enabling the apoptosis of
oral cancer cells through receptor binding with serine threonine
kinase 3 (Nanda and others 2004; Baba and others 2013). Rat
experiments have proven that the ethyl acetate extracts of Japanese
black vinegars can inhibit azoxymethane-induced colon cancer by
increasing glutathione sulfur enzymes and quinone reductase in the
liver and extend the life of these rats (Shimoji and others 2003,
2004). According to the results of epidemiological investigations,
the incidence of esophageal cancer in Linzhou (Henan, China) is
negatively correlated with grain vinegars consumption (Sun and
others 2003). Except for the sugarcane vinegar (Mimura and oth-
ers 2004), research on the anticancer activities of fruit vinegars has
not yet been published. Nevertheless, according to investigations
on the anticancer activities of polyphenols (such as resveratrol) in
some fruits (Shukla and Singh 2011; Peng and others 2014; Kyrø
and others 2015; Zamora-Ros and others 2015), the long-term
intake of fruit vinegars may have a positive anticancer effect in
humans as well.
Other properties
In addition to the above-mentioned properties, vinegars also
improve appetite (Xu and others 2003), reduce fatigue (Lu and
Zhou 2002; Zhang and others 2007), and prevent osteoporosis
(Kishi and others 1999) (Table 1), but little research on these
topics has been published.
Active Ingredients and Their Functional Mechanisms
Many investigations on the active ingredients of vinegars and
their corresponding functional mechanisms have been performed.
To date, the active compounds identified in vinegars mainly
include organic acids, polyphenols, melanoidins, ligustrazine,
caffeoylsophorose, and tryptophol. In the following sections, these
compounds and their functional mechanisms will be reviewed.
Organic acids
Mechanism of the antibacterial effects of organic acids. Or-
ganic acids in vinegars inhibit the growth of bacteria through the
following ways (Figure 1) (Zhang and others 2011): (1) destroying
the outer membrane of bacteria, (2) inhibiting macromolecular
synthesis, (3) consuming the energy of bacteria, (4) increasing in-
tracellular osmotic pressure, and (5) promoting the generation of
antibacterial peptides in host cells.
The fat-soluble properties of undissociated organic acids allow
them to travel through the cell membrane, become dissociated
at intracellular neutral pH values, produce hydrogen ions, and
reduce the intracellular pH (Hirshfield and others 2003). First, a
decrease in the intracellular pH leads to the protonation of the car-
boxyl and phosphate groups of lipopolysaccharides on the bacterial
cell membrane, undermining its stability (Brul and Coote 1999;
Alakomi and others 2000). Second, the lower intracellular pH
also affects the enzymatic activities and inhibits DNA replication
and transcription as well as protein expression (Cherrington and
others 1991). To stabilize the intracellular pH, bacteria must re-
lease hydrogen ions via active transport, but this process consumes
adenosine triphosphate (ATP) and affects the normal growth of
bacteria (Axe and Bailey 1995; Zhang and others 2011). In ad-
dition, anions dissociated from organic acids and potassium ions
must be pumped from the extracellular fluid (exchanged with hy-
drogen ions) (Figure 1), which significantly increases the intracel-
lular osmotic pressure and leads to breakage of the cell membrane
(McLaggan and others 1994; Alakomi and others 2000). Thus,
bacteria must release several necessary nutrients, such as glutamic
acid ions, to balance the intracellular osmotic pressure, which in-
hibits the normal growth of bacteria (Figure 1) (Roe and others
1998). In addition to the direct inhibition of growth, several stud-
ies have shown that lactic acid, butyric acid, and other organic
acids cause the host cells to produce antimicrobial peptides, which
destroy the bacterial outer membrane and indirectly inhibit their
growth at the gene transcription and translation level (Figure 1)
(Brogden 2005; Ochoa-Zarzosa and others 2009).
Mechanism of the acetic acid–induced control of blood glucose
levels. The acetic acid in vinegars regulates the concentration of
blood glucose in the following ways (Petsiou and others 2014): (1)
delaying gastric emptying, (2) inhibiting disaccharidase activity, (3)
improving insulin sensitivity, and (4) promoting the production of
glycogen.
Postprandial blood sugar levels are primarily determined by the
rate that glucose enters the blood and is consumed in vivo. The
rate that glucose enters the blood is determined by the rate of
gastric emptying, digestion, and absorption in the small intestine.
Animal experiments have shown that organic acids delay the emp-
tying of the stomach by stimulating the duodenum or the receptor
in the first 150 cm of the small intestine due to the acidity of
organic acids (Lin and others 1990). The results of experiments
performed on the effects of vinegar on the gastric emptying rate
(via real-time ultrasound imaging) of patients with type 1 diabetes
have shown that 30 mL of apple vinegar can reduce the postpran-
dial gastric emptying rate by 10% (Hlebowicz and others 2007),
which was consistent with the earlier experimental results of using
acetaminophen as a marker to study the effects of vinegar on the
gastric emptying rate (Liljeberg and Bj ¨
orck 1998). To explore the
C2016 Institute of Food Technologists®Vol. 00, 2016 rComprehensive Reviews in Food Science and Food Safety 5
Vinegar functions on health . . .
Figure 1–Mechanism of the antimicrobial effects of organic acids (Zhang and others 2011).
effect of organic acids on postprandial glucose absorption, Ogawa
and others (2000) used a nutrient solution containing 5 mmol/L
of organic acids to cultivate Caco-2 cells and found that acetic acid
significantly inhibited the activity of disaccharidase (sucrase, mal-
tase, lactase, and trehalose), but the other organic acids (lactic acid,
citric acid, fumaric acid, tartaric acid, succinic acid, and methy-
lene succinic acid) did not show significant effects on inhibition.
Further experiments have proven that acetic acid does not affect
the de novo synthesis of disaccharide (at the gene transcription and
translation levels); thus, the acetic acid–induced inhibition of the
disaccharide activity may occur during the posttranscription phase
(Ogawa and others 2000), which explains why vinegar does not
affect the increase in blood glucose levels due to the consumption
of monosaccharide beverages (Johnston and others 2010).
In addition to reducing the rate of which glucose enters the
blood, increasing the consumption of blood glucose is also an
effective way to control postprandial blood glucose levels. An-
imal experiments have revealed that the consumption of acetic
acid promotes the transformation of blood glucose in the liver
and muscles to glycogen through the accumulation of glucose-
6-phosphate (Fushimi and Sato 2007). The in vivo regulation of
glucose metabolism by acetic acid is primarily achieved through
the activation of the adenosine monophosphate-activated protein
kinase (AMPK) pathway (Figure 2) (Sakakibara and others 2006).
Acetic acid is a building block for the synthesis of acetyl coen-
zyme A (acetyl-CoA). During the synthesis of acetyl-CoA, ATP
is consumed and adenosine monophosphate (AMP) is generated,
which increases the AMP/ATP ratio, activating the AMPK path-
way. The activation of the AMPK pathway reduces blood glucose
levels and increases glycogen reserves by directly inhibiting the
gene expression of related enzymes involved in glycometabolism.
Besides, activation of the AMPK pathway also reduces the concen-
tration of triglycerides by inhibiting the gene expression of related
lipid metabolism enzymes, which reduces blood glucose levels
by increasing insulin sensitivity and decreasing insulin resistance
(Figure 2) (Sakakibara and others 2006). The aforementioned fea-
tures of acetic acid indicate that vinegar ingestion at bedtime can
help patients with type 2 diabetes to moderate their waking glu-
cose concentration in the next day (White and Johnston 2007).
Mechanism of the regulation of lipid metabolism by acetic acid.
Similar to blood glucose metabolism, acetic acid in vinegar also
decreases the synthesis of lipids and increases the excretion and
decomposition of lipids by activating the AMPK pathway in vivo
(Figure 3) (Sakakibara and others 2006; Yamashita and others
2014). During the conversion of acetic acid into acetyl-CoA,
the activation of the AMPK pathway leads to a reduction in the
concentration of cholesterol, triglycerides, and LDL by down-
regulating the expression of the srebp-1 gene. Besides, activated
AMPK also inhibits the expression of a series of genes related to
fatty acid synthesis through the phosphorylation of carbohydrate
response element binding protein (ChREBP), which reduces the
synthesis of fatty acids (Figure 3) (Sakakibara and others 2006,
2010; Yamashita and others 2014). In addition, acetic acid reduces
the blood lipid content of rats by promoting the oxygenolysis of
fatty acids and the secretion of bile (Fushimi and others 2006);
however, further research is required to determine whether these
functional properties are prevalent in humans.
Mechanism of weight loss due to acetic acid. Acetic acid in
vinegar affects weight loss through the following mechanisms: (1)
decreasing the synthesis of lipids, (2) increasing the oxygenolysis
and secretion of lipids, (3) increasing postprandial satiety, and (4)
increasing energy consumption. The first 2 methods are similar
6Comprehensive Reviews in Food Science and Food Safety rVol.00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
AMPK pathway
g6-pase pepck srebp-1
G6-Pase ↓PEPCK ↓SREBP-1 ↓
Triglyceride ↓
Insulin sensitivity
↑
Insulin resistance ↓
G6-P↑Glucose ↓
Phosphoenolpyruvic acid
Oxaloacetic acid
G6-Pase
↓
PEPCK ↓
Glycogen ↑
Liver
Liver and muscle
Acetic acid + ATP →Acetyl-CoA+ ppi + AMP AMP/ATP ↑
ATP: Adenosine triphosphate; CoA: Coenzyme A; ppi: Pyrophosphoric acid; AMP: Adenosine monophosphate;
AMPK: AMP-activated protein kinase; G6-P: Glucose-6-phosphate; G6-Pase: G6-P kinase;
PEPCK: Phosphoenolpyruvate carboxykinase; SREBP-1: Sterol regulatory element-binding protein-1
Figure 2–Acetic acid reduces the blood sugar content by activating AMPK (Sakakibara and others 2006).
AMPK pathway
srebp-1
SREBP-1
↓
Cholesterol
↓
Triglyceride
↓
LDL
↓
Acetic acid + ATP
→
Acetyl-CoA + ppi + AMP
AMP/ATP
↑
lpk
g6pd
me
acl
fas
fcc
Phosphorylated
ChREBP
Glucose
Pyruvic
acid
LPK
↓
Pentose
phosphate
pathway
TCA
Malic
acid
Citric acid
Acetyl-CoA
ACL
↓
ACC
↓
FAS
↓
Fatty acid
↓
NADP+
NADPH
ME
↓
ME↓
Acetyl-CoA
ATP: Adenosine triphosphate; CoA: Coenzyme A; ppi: Pyrophosphoric acid; AMP: Adenosine
monophosphate; AMPK: AMP-activated protein kinase; SREBP-1: Sterol regulatory element-binding
protein-1; ChREBP: Carbohydrates response element-binding protein; LPK: Pyruvate kinase; G6PD:
Glucose-6-phosphate dehydrogenase; ME: Malic enzyme; ACL: ATP-citrate lyase; ACC: Acetyl-CoA
carboxylase; FAC: Fatty acid synthetase; LDL: Low-density lipoprotein; TCA: Tricarboxylic acid cycle
Figure 3–Acetic acid reduces the synthesis of lipids by activating AMPK (Sakakibara and others 2006; Yamashita and others 2014).
C2016 Institute of Food Technologists®Vol. 00, 2016 rComprehensive Reviews in Food Science and Food Safety 7
Vinegar functions on health . . .
to those in the regulation of lipid metabolism (see the section
Mechanism of the regulation of lipid metabolism by acetic acid),
whereas the third mechanism is similar to the mechanism of
blood sugar control (see the section Mechanism of the acetic
acid-induced control of blood glucose levels), wherein acetic acid
increases postprandial satiety by stabilizing postprandial blood
glucose levels, thereby reducing dietary intake. In addition, acetic
acid also increases biological energy consumption by increasing
myoglobin levels and upregulating the expression of genes related
to the synthesis of fatty acids (Kondo and others 2009a; Yamashita
and others 2009; Hattori and others 2010).
Polyphenols
Mechanism of the antibacterial effects of polyphenols. The an-
tibacterial activities of the polyphenols present in vinegars are pri-
marily achieved by destroying the integrity of the cell membrane
and interfering with the activities of enzymes present in bacte-
ria (Yoda and others 2004; Taguri and others 2006; Gradiˇ
sar and
others 2007; Sirk and others 2008). Polyphenols combine with
the peptidoglycan and phospholipid bilayer of the outer mem-
brane of bacteria to reduce the integrity of the cell membrane
(Yoda and others 2004; Sirk and others 2008). In addition, be-
cause polyphenols are a type of polyol, these compounds affect
the activities of bacterial intracellular enzymes by reacting with
the amino and carboxyl groups of proteins as well as the chelating
transition metal ion (coenzyme) (Taguri and others 2006; Gradiˇ
sar
and others 2007) to inhibit the growth of bacteria.
Antioxidation mechanism of polyphenols. The antioxidant ac-
tivities of polyphenols in vinegar include the abilities to scavenge
free radicals, chelate transition metal ions, and reduce oxidants
(Rice-Evans and others 1996; Sang and others 2007; Perron and
Brumaghim 2009). As an aromatic compound, the conjugated
π-bond system on the benzene ring of polyphenols provides a
stabilizing effect to free radicals and can effectively block free rad-
ical chain reactions (Rice-Evans and others 1996). The hydroxyl
structure on the benzene ring of polyphenols (similar to cate-
chols) can effectively chelate transition metal ions, thus preventing
oxidation reactions (Perron and Brumaghim 2009). In addition,
the phenolic hydroxyl group on the benzene ring of polyphenols
can be oxidized to quinone in redox reactions; thus polyphenols
also have a reducing effect (Sang and others 2007).
Melanoidins
Mechanism of the antibacterial effect of melanoidins.
Melanoidins are brown macromolecular compounds produced by
the reduction of sugars and proteins (or amino acids) through the
Maillard reaction (Wang and others 2011). The antibacterial ac-
tivities of melanoidins present in vinegar are due to their ability to
chelate metal ions (Ruri´
an-Henares and Morales 2008; Rufian-
Henares and de la Cueva 2009). Melanoidins are macromolecu-
lar compounds with a negative charge, hence, melanoidins have
strong chelating abilities for metal ions (Wang and others 2011). At
low concentrations, melanoidins chelate iron ions, affecting their
absorption and utilization, which inhibit the growth of bacteria.
At high concentrations, melanoidins destroy the cell membrane
of bacteria by chelating magnesium ions, resulting in the death of
the bacteria (Ruri´
an-Henares and Morales 2008; Rufian-Henares
and de la Cueva 2009).
Mechanism of the antioxidation effect of melanoidins. The
mechanism of the antioxidation effects of melanoidins in vinegar
is similar to that of polyphenols. The antioxidation activities
of melanoidins mainly include the abilities to chelate transition
Figure 4–Structure of ligustrazine.
Figure 5–Structure of caffeoylsophorose (Matsui and others 2014).
Figure 6–Structure of tryptophol (Inagaki and others 2007).
metal ions and scavenge free radicals, as well as the power to
act as a reducing agent (Wang and others 2011). Owing to their
negative charge and macromolecular properties, melanoidins
have strong chelating abilities for transition metal ions, effectively
preventing oxidation reactions induced by transition metal ions.
In addition, melanoidins are a type of macromolecule polymer,
containing a large conjugated π-bond system and abundant
reduction ketone structures. As a result, melanoidins possess good
radical-scavenging abilities and reducing powers (Wang and others
2011).
Mechanism of the improvement in circulation due to
ligustrazine
Ligustrazine (Figure 4) effectively improves blood circulation by
inhibiting platelet aggregation and expanding blood vessels in vivo
(Cauvin and others 1983; Zhou and others 1985; Wang and others
2009; Ren and others 2012). Studies have shown that ligustrazine is
a good calcium channel blocker (Ren and others 2012), which can
inhibit the aggregation of platelets (platelet aggregation is positively
correlated with the concentration of intracellular calcium ions)
(Zhou and others 1985), and the contraction of muscle cells on
blood vessels (the internal flow of intracellular calcium ions can
lead to the contraction of muscle) (Cauvin and others 1983) by
reducing the internal flow of calcium ion in cells, which improves
blood circulation. In addition, ligustrazine can pass the blood–
brain barrier, so it is also used in the treatment of cerebrovascular
diseases as well as cardiovascular diseases (Wang and others 2009).
Mechanism of the hypoglycemic effects of caffeoyl-
sophorose
Caffeoylsophorose (Figure 5) is a novel, natural α-glucosidase
inhibitor that was isolated from the purple sweet potato vinegar by
Matsui and others (2014). Rat experiments have showed that the
consumption of 0.1 g/kg body weight of caffeoylsophorose can
decrease postprandial blood glucose contents by approximately
11.1% and reduce the secretion of insulin. However, caffeoyl-
sophorose did not have a significant effect when the diet consisted
8Comprehensive Reviews in Food Science and Food Safety rVol.00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
Table 2–Polyphenol compounds in vinegars.
Vinegar type Country
Detection
method Polyphenolic compounds; µg/mL Reference
Shanxi aged
vinegar
China LC-MS Protocatechuic
acid (5.00)
Dihydroferulic
acid (3.75)
Dihydrosinapic acid
(2.56)
P-hydroxybenzoic
acid (2.05)
Salicylic acid
(1.49)
P-coumaric acid
(0.90)
Ferulic acid (0.34) Sinapic acid (0.41) Chen and others
2015
Kurosu Japan LC-PDA Dihydroferulic
acid (24.8)
Dihydrosinapic
acid (4.68)
Vanillic acid
(1.44)
Sinapic acid
(1.15)
Ferulic acid
(0.95)
P-hydroxycinnamic
acid (0.17)
/ / Shimoji and others
2002
Balsamic vinegar Italy GC-MS Protocatechuic
acid (18.8)
Gallic acid (18.0) P-coumaric acid
(17.1)
Syringic acid
(13.8)
Caffeic acid
(10.9)
Ferulic acid
(8.8)
Vanillic acid
(8.1)
P-hydroxybenzoic
acid(6.5)
Plessi and others
2006
Sherry vinegar Spain LC-PDA Gallic acid
(447.8)
Caftaric acid
(67.4)
Ethyl gallate (52.4) Protocatechu
aldehyde
(28.6)
Syringaldehyde
(13.0)
P-coumaric acid
ethyl ester
(12.4)
Vanilline (5.2) Caffeic acid(3.0) Parrilla and others
1999
Red wine vinegar Spain LC-MS Malvidin-3-
glucoside
(53.04)
Malvidin-3-(6-
acetyl)
-glucoside
(26.3)
Malvidin-3-glucoside
-4-vinyl (Vitisin B)
(14.25)
Acetyl vitisin B
(11.77)
Carboxy-
pyranomalvidin-
3-glucoside
(vitisin A)
(9.03)
Malvidin3-(6-p-
coumaroyl)
-glucoside (8.2)
Malvidin-3-
glucoside-ethyl-
(epi)catechin
(7.76)
Catechyl-
Pyranocyanidin
-3-glucoside
(5.63)
Cerezo and others
2010
Red wine vinegar
(Tradition)
Turkey LC-PDA Gallic acid
(16.36)
Catechin (13.76) Caffeic acid
(6.30)
Epicatechin
(4.96)
Chlorogenic acid
(3.73)
Syringic acid
(0.70)
P-coumaric acid
(0.23)
Ferulic acid
(0.06)
Budak and
Guzel-Seydim
2010
Red wine vinegar
(Industry)
Turkey LC-PDA Gallic acid
(18.23)
Catechin (27.50) Caffeic acid (10.30) Epicatechin
(8.2)
Chlorogenic acid
(0.16)
Syringic acid
(0.33)
P-coumaric acid
(0.56)
Ferulic acid
(0.35)
Budak and
Guzel-Seydim
2010
Red wine vinegar Germany LC-MS Epicatechin (22) Caffeic acid (6.7) Malvidin 3-glucoside
(3.8)
Malvidin3-
glucoside
acetate (1.7)
Petunidin3-
glucoside
(1.3)
Delphinidin3-
glucoside
(1.3)
Peonidin3-
glucoside
(1.2)
Malvidin3-
glucoside
coumarate (0.9)
Andlauer and
others 2000
White wine vinegar Germany LC-MS Catechin (24.0) Protocatechuic
acid (4.1)
Caffeic acid (1.1) / / / / / Andlauer and
others 2000
Grape vinegar Korea LC-PDA Epigallocatechin
(10.75)
Epicatechin
(0.82)
Catechin
(0.78)
Gallic acid
(0.74)
Chlorogenic acid
(0.2)
Epigallocatechin
gallate (0.02)
/ / Jeong and others
2009
Apple vinegar Turkey LC-PDA Chlorogenic acid
(347.7)
Catechuic acid
(68.2)
Gallic acid
(61.2)
Caffeic acid
(17.2)
/ / / / Aykın and others
2015
Apple vinegar China LC-PDA Chlorogenic acid
(6.56)
Caffeic acid
(3.03)
Phlorizin
(1.76)
Epigallocatechin
gallate
(0.77)
Gallic acid
(0.35)
P-coumaric acid
(0.33)
Ferulic acid (0.24) Vanillic acid
(0.06)
Li and others 2013
Apple vinegar Japan LC-MS Chlorogenic acid
(196)
4-p-
coumaroylquinic
acid (135.0)
Isomer of chlorogenic
acid (31.0)
Isomer of p-
coumaroylquinic
acid (25.0)
Isomer of
chlorogenic
acid (13.0)
P-hydroxybenzoic
acid
(7.7)
Caffeic acid
(7.6)
Protocatechuic
acid (4.1)
Nakamura and
others 2010
Apple vinegar Germany LC-MS Chlorogenic
acid/Caffeic
acid(180)
Catechin (58) P-coumaroylquinic
acid (51)
Phlorizin (41) Phloretin-xyl-glc
(30)
Protocatechuic
acid (20)
Quercitrin
(20)
Epicatechin
(11)
Andlauer and
others 2000
Pomegranate
vinegar
Turkey LC-PDA Gallic acid(67.8) Caffeic acid (47) Caffeic acid
(13.4)
/ / / / / Aykın and others
2015
(Continued).
C2016 Institute of Food Technologists®Vol. 00, 2016 rComprehensive Reviews in Food Science and Food Safety 9
Vinegar functions on health . . .
Table 2–Continued
Vinegar type Country
Detection
method Polyphenolic compounds; µg/mL Reference
Kiwi vinegar China LC-PDA Gallic acid(9.67) Chlorogenic acid
(3.12)
Vanillic acid
(1.78)
Catechin
(1.47)
Phlorizin
(0.49)
P-coumaric acid
(0.34)
Caffeic acid (0.04) Ferulicacid
(0.01)
Li and others 2013
Persimmon vinegar China LC-PDA Gallic
acid(22.92)
Vanillic acid
(0.96)
Phlorizin (0.38) Catechin
(0.16)
Epigallocatechin
gallate (0.13)
Chlorogenic acid
(0.06)
Caffeic acid (0.04) P-coumaric acid
(0.03)
Li and others 2013
Persimmon vinegar Korea LC-PDA Gallic
acid(14.24)
Epigallocatechin
(11.98)
Catechin
(4.42)
Epicatechin (2.23) Chlorogenic acid
(1.01)
Epigallocatechin
gallate (0.02)
/ / Jeong and others
2009
Plum vinegar Korea LC-PDA Epigallocatechin
(6.04)
Epicatechin
(0.29)
Catechin
(0.27)
Chlorogenic acid
(0.21)
Gallic acid (0.03) Epigallocatechin
gallate (0.03)
/ / Jeong and others
2009
Sugarcane vinegar Egypt LC-PDA Benzoic acid
(3.6)
Catechin
(2.1)
Gallic acid
(0.3)
Ferulic acid
(0.1)
/ / / / Soltan and
Shehata 2012
Coconut vinegar Egypt LC-PDA Catechin (4.3) Benzoic acid
(3.6)
Salicylic acid
(2.1)
Gallic acid
(0.3)
Caffeic acid
(0.1)
Ferulic acid
(0.1)
/ / Soltan and
Shehata 2012
Palm vinegar Egypt LC-PDA Salicylic acid
(85.0)
Coumarin
(2.9)
Gallic acid
(0.2)
Ferulic acid
(0.2)
Caffeic acid
(0.1)
///Soltanand
Shehata 2012
Abbreviations: GC, gas chromatography; LC, liquid chromatography; MS, mass spectrometry; PDA, photodiode array detector.
of monosaccharides (Matsui and others 2014). Further studies
indicated that the hypoglycemic effect of caffeoylsophorose was
related to its structure, including the phenolic hydroxyl group
and the unsaturated acyl hydrocarbon, which reduced the rate
of polysaccharide decomposition in the small intestine through
noncompetitive inhibition of α-glucosidase, which reduced the
concentration of postprandial blood glucose (Matsui and others
2014).
Anticancer mechanism of tryptophol
Tryptophol (Figure 6) is a novel anticancer compound that was
isolated from Japanese black soybean vinegar by Inagaki and oth-
ers (2007). Cell experiments have shown that tryptophol denatures
DNA repair enzymes by activating caspase-8 and -3, which in-
hibits the proliferation of human leukemia cells (U937) in vitro.
Tryptophol was less toxic to normal lymphocytes and did not
activate the caspase of lymphocytes (Inagaki and others 2007).
The sources of functional ingredients in vinegars
A number of investigations have proven that the aforementioned
functional constituents of vinegars are derived from the raw ma-
terials, microorganisms, and technological conditions employed
during the fermentation process.
Functional ingredients from raw materials
Organic acids. Organic acids are the major functional and fla-
vor ingredients of vinegars and are mainly produced during the
fermentation stage. However, some organic acids in vinegars are
derived from the raw materials, especially in fruit vinegars. For
example, several studies have revealed that grape, apple, and other
types of fruit that are commonly used as raw materials of fruit
vinegars contain tartaric acid, malic acid, citric acid, and other
nonvolatile organic acids, and that their total contents can reach
0.5%–2% of the total acid quantity of fruits (Rodriguez and oth-
ers 1992; Guo and others 2012; Cheng and others 2013). In
contrast, the organic acid contents of sorghum, rice, and wheat
grain, which are common raw materials for grain vinegars, are
very low, amounting to only 0.1% of the total raw materials (Yuan
and others 2011).
Polyphenols. Polyphenols present in vinegars are mainly de-
rived from the raw materials (Solieri and Giudici 2009), but the
types and contents of polyphenols in each type of vinegar are dif-
ferent due to differences in the raw materials and manufacturing
processes (Table 2). Grain vinegars mainly contain protocatechuic
acid, ferulic acid, and sinapic acid (most of the ferulic acid and
sinapic acid are reduced to dihydroferulic acid, and dihydrosinapic
acid during the fermentation process) (Shimoji and others 2002;
Chen and others 2015). In contrast, grain vinegars contain only
a small amount of gallic acid, catechins, and other phenolic com-
pounds, which are high in fruit vinegars (Garcı́a Parrilla and others
1999; Andlauer and others 2000; Plessi and others 2006; Jeong and
others 2009; Budak and Guzel-Seydim 2010; Cerezo and others
2010). Apple vinegars contain large amounts of chlorogenic acid,
which is present in the raw material (Andlauer and others 2000;
Nakamura and others 2010; Li and others 2013; Aykın and others
2015). In addition, the fermentation process also affects the types
and contents of polyphenols. For instance, acetic acid fermentation
reduces the polyphenol content of vinegars (Andlauer and others
2000), and the wooden containers used in the aging process also
influence the types and contents of polyphenols present in fruit
vinegars (Garcı́a Parrilla and others 1999).
10 ComprehensiveReviews in Food Science and Food Safety rVol. 00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
Figure 7–Proposed pathway for the biosynthesis of ligustrazine (Dickschat and others 2010).
Functional ingredients from microbial fermentation
Organic acids. Organic acids in vinegars are mainly produced
by microorganisms during the fermentation stage (Solieri and Giu-
dici 2009). Organic acids in vinegars can be considered volatile
(organic acids without hydroxyl groups, such as acetic acid and
propionic acid) or nonvolatile (organic acids with hydroxyl groups
such as lactic acid and tartaric acid) acids, according to their chem-
ical properties (Xu 2008). Among them, acetic acid is the main
organic acid present in vinegars and is one of the most important
functional ingredients. Acetic acid is mainly produced by acetic
acid bacteria during the fermentation stage (Xu 2008). Lactic
acid, which shows the highest content among nonvolatile organic
acids in vinegars, is mainly produced during the alcoholic fer-
mentation stage (Xu 2008). Propionic acid, tartaric acid, malic
acid, citric acid, and other organic acids in vinegars are produced
throughout the whole fermentation stage (Xu 2008). Moreover,
the fermentation conditions also influence the contents of organic
acids. Heating, steaming, and fermenting techniques used during
the fermentation process reduce the contents of volatile organic
acids and water, which increases the contents of nonvolatile or-
ganic acids, and thereby the ratios of nonvolatile organic acids to
volatile organic acids (Xu 2008).
Ligustrazine. Ligustrazine (Figure 4), which is also called
tetramethyl pyrazine, can inhibit platelet aggregation, expand
blood vessels, and promote blood circulation (Cauvin and others
1983; Zhou and others 1985; Wang and others 2009). Therefore,
ligustrazine is often used in the treatment of ischemic cerebrovas-
cular disease (Zhou and others 1985). Initially, ligustrazine was
obtained from natto, a fermented food, and was used as a flavoring
composition by Kosuge and Kamiya (1962), who thought that it
might be a secondary metabolite of Bacillus subtilis. Ligustrazine
was identified in vinegar by Kosuge and others (1971), and its
corresponding content reached 1.5 μg/kg. The ability of ligus-
trazine to improve blood circulation was discovered by Beijing
Pharmaceutical Research Institute in 1977, based on the tradi-
tional Chinese medicine “Guanxin Prescription 2” and “Little
Guanxin Prescription 2” (Ligusticum wallichii and Carthamus tincto-
rius) (Anonymous 1977). Many studies have indicated that the pro-
duction of ligustrazine by microorganisms is due to the transfor-
mation of acetoin (3-hydroxy-2-butanone) (Figure 7) (Dickschat
and others 2010).
Dihydroferulic acid and dihydrosinapic acid. Dihydroferulic
acid and dihydrosinapic acid (Figure 8) were isolated from Kurosu,
a Japanese vinegar, by Shimoji and others (2002). These two com-
pounds were the main radical-scavenging components in Kurosu,
but were not present in the primary raw material, unpolished rice
(Shimoji and others 2002). Based on the compositional analysis
of Kurosu and its raw materials as well as the results of previous
studies, dihydroferulic acid and dihydrosinapic acid were likely
produced through the reduction of ferulic acid and sinapic acid
in unpolished rice by microorganisms during the fermentation
process, respectively (Shimoji and others 2002).
C2016 Institute of Food Technologists®Vol.00,2016 rComprehensiveReviewsinFoodScience and Food Safety 11
Vinegar functions on health . . .
Figure 8–Structures of ferulic acid, dihydroferulic acid, sinapic acid, and
dihydrosinapic acid (Shimoji and others 2002).
Tryptophol. Tryptophol (Figure 6), which shows anticancer ac-
tivities, was isolated from Japanese black soybean vinegar by Baba
and others (2013). Composition analyses revealed that tryptophol
did not exist in black beans, rice, and distiller’s yeast (Baba and oth-
ers 2013). Thus, tryptophol may be produced by microorganisms
during the fermentation process.
Functional ingredients produced by chemical reactions
during fermentation
Melanoidins. Melanoidins are brown macromolecular com-
pounds produced by the reduction of sugar and protein (or
polypeptide, amino acid) through the Maillard reaction (Wang
and others 2011). In vinegars, melanoidins are mainly produced
during the baking (grain vinegars), steaming (grain vinegars), and
aging process (grain vinegars and fruit vinegars) (Tagliazucchi and
others 2010; Yang and others 2014). In addition to the reaction of
sugars and amino acids, phenolic compounds in vinegars can also
polymerize with melanoidins, becoming a part of their skeleton,
which increases the antioxidant capacity (Tagliazucchi and others
2010). The majority of melanoidins in vinegars possess molecular
weights ranging from 10 to 80 KDa (Tagliazucchi and others 2010;
Wang and others 2011; Yang and others 2014).
Ligustrazine. Ligustrazine was identified (see the section Ligus-
trazine of Functional ingredients from microbial fermentation;
produced by microorganisms) in vinegars as early as 1971, but
its content was very low (1.5 μg/kg), and it only was used as a
fragrance ingredient. Ligustrazine was first proposed by He and
others (2004) to be a functional component of vinegars. After 2
months of aging, the content of ligustrazine in Zhenjiang aromatic
vinegar reached 77 μg/mL (He and others 2004). In vinegars,
ligustrazine is produced through the Maillard reaction during the
baking, steaming, and aging processes, which could be the reason
why the ligustrazine content of Zhenjiang vinegar (through bak-
ing and aging) was higher than that of the samples tested in 1971
(Kosuge and others 1971; He and others 2004). The mechanism
of ligustrazine formation in vinegars through the Maillard reaction
is shown in Figure 9 (Rizz 1972). Although data on the presence
of ligustrazine in fruit vinegars have not been reported, based on
the process used for the production of fruit vinegars (mixed mi-
crobial fermentation, aging for a long time), fruit vinegars may
also contain a certain amount of ligustrazine.
Figure 9–Proposed pathway for the formation of ligustrazine in the
Maillard reaction (Rizz 1972).
Conclusion
Vinegar is an acidic condiment with a variety of functional prop-
erties, including antibacteria, anti-infection, antioxidation, anti-
cancer activities, blood glucose control, lipid metabolism regula-
tion, and weight loss. The antibacterial and anti-infection effects of
vinegars are mainly due to the presence of organic acids, although
polyphenols and melanoidins in some vinegars also contribute to
these properties. The antioxidant abilities of vinegars are mainly
derived from polyphenols and melanoidins, which are affected by
the raw materials and fermentation conditions, respectively. The
effects of some vinegars on blood glucose control, lipid metabolism
regulation, and weight loss are due to the presence of acetic acid,
which is mainly produced by acetic acid bacteria during fermen-
tation. Furthermore, caffeoylsophorose (inhibits disaccharidase),
ligustrazine (improves blood circulation), and other functional in-
gredients in vinegars also provide assistance. In terms of its an-
ticancer properties, some vinegars strongly inhibit the growth of
cancer cells in vivo or in vitro. However, these results were pri-
marily obtained from cell or animal experiments, and the identity
of the responsible functional ingredient remains unclear, except
for tryptophol, which occurs in Japanese black soybean vinegar.
Both grain and fruit vinegars contain these functional ingredi-
ents, including organic acids (especially acetic acid), polyphenols,
and melanoidins. Researches on the properties of acetic acid have
primarily focused on fruit vinegars. The other functional ingredi-
ents, such as ligustrazine, dihydroferulic acid, dihydrosinapic acid,
tryptophol, and caffeoylsophorose, were all found in grain vine-
gars. In addition, phenyllactic acid, a highly effective antibacterial
compound, was isolated and identified from Shanxi aged vinegar
(unpublished data 2016).
Owing to its properties and components, vinegar is not just an
acidic condiment, several types of vinegars, especially those pro-
duced through traditional fermentation technologies, including
Shanxi aged vinegar, Zhenjiang aromatic vinegar, Sichuan Baon-
ing bran vinegar, Fujian Yongchun Monascus vinegar, Japanese
black vinegar, Italian balsamic vinegar, and other fruit vinegars
could be developed into functional foods. Through the discov-
ery of various functional ingredients and the clarification of their
mechanisms, some vinegars and vinegar derivatives could be used
as pharmaceutical agents to prevent chronic diseases such as dia-
betes and cardiovascular disease.
12 ComprehensiveReviews in Food Science and Food Safety rVol. 00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
Acknowledgments
The authors have declared that no conflicting interest exists.
This review was supported by Programs of International S &
T Cooperation, Ministry of Science and Technology, People’s
Republic of China (no. 2014DFG32380) and the Fundamental
Research Funds for the Central Universities (nos. 2013PY006,
2014PY034, and 2662015PY167), and the project of Wuhan Sci-
ence & Technology Bureau (no. 2015030809020368).
References
Alakomi HL, Skytt¨
a E, Saarela M, Mattila-Sandholm T, Latva-Kala K,
Helander I. 2000. Lactic acid permeabilizes Gram-negative bacteria by
disrupting the outer membrane. Appl Environ Microbiol 66:2001–5.
Aminifarshidmehr N. 1996. The management of chronic suppurative otitis
media with acid media solution. Am J Otol 17:24–5.
Andlauer W, Stumpf C, F¨
urst P. 2000. Influence of the acetification process
on phenolic compounds. J Agric Food Chem 48:3533–6.
Anonymous. 1977. Experimental study and clinical observation of
ligustrazine. New Med J 4:45.
Axe DD, Bailey JE. 1995. Transport of lactate and acetate through the
energized cytoplasmic membrane of Escherichia coli. Biotechnol Bioeng
47:8–19.
AykınE,BudakNH,G
¨
uzel-Seydim ZB. 2015. Bioactive components of
mother vinegar. J Am Coll Nutr 34:80–9.
Baba N, Higashi Y, Kanekura T. 2013. Japanese black vinegar “Izumi”
inhibits the proliferation of human squamous cell carcinoma cells via
necroptosis. Nutr Cancer 65:1093–97.
Beheshti Z, Chan YH, Nia HS, Hajihosseini F, Nazari R, Shaabani M. 2012.
Influence of apple cider vinegar on blood lipids. Life Sci J 9:2431–40.
Bertelli D, Maietti A, Papotti G, Tedeschi P, Bonetti G, Graziosi R,
Brandolini V, Plessi M. 2015. Antioxidant activity, phenolic compounds,
and NMR characterization of balsamic and traditional balsamic vinegar of
modena. Food Anal Method 8:371–9.
Brighenti F, Castellani G, Benini L, Casiraghi M, Leopardi E, Crovetti R,
Testolin G. 1995. Effect of neutralized and native vinegar on blood glucose
and acetate responses to a mixed meal in healthy subjects. Eur J Clin Nutr
49:242–7.
Brogden KA. 2005. Antimicrobial peptides: pore formers or metabolic
inhibitors in bacteria? Nature Rev Microbiol 3:238–50.
Brul S, Coote P. 1999. Preservative agents in foods: mode of action and
microbial resistance mechanisms. Int J Food Microbiol 50:1–17.
Budak HN, Guzel-Seydim ZB. 2010. Antioxidant activity and phenolic
content of wine vinegars produced by two different techniques. J Sci Food
Agric 90:2021–6.
Budak NH, Aykin E, Seydim AC, Greene AK, Guzel-Seydim ZB. 2014.
Functional properties of vinegar. J Food Sci 79:R757–64.
Cauvin C, Loutzenhiser R, Breemen C. 1983. Mechanisms of calcium
antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol 23:373–96.
Cerezo AB, Cuevas E, Winterhalter P, Carmen Garcia-Parrilla M, Troncoso
AM. 2010. Anthocyanin composition in Cabernet Sauvignon red wine
vinegar obtained by submerged acetification. Food Res Int 43:1577–84.
Chang JM, Fang TJ. 2007. Survival of Escherichia coli O157:H7 and Salmonella
enterica serovars Typhimurium in iceberg lettuce and the antimicrobial effect
of rice vinegar against E. coli O157:H7. Food Microbiol 24:745–51.
Chen F, Gullo M. 2015. 4th international conference on acetic acid
bacteria-vinegar and other products (AAB 2015). Acetic Acid Bacteria 4:17.
Chen H, Zhou Y, Shao Y, Chen F. 2015. Free phenolic acids in Shanxi aged
vinegar: changes during aging and synergistic antioxidant activities. Int J
Food Prop 19:1183–93.
Cheng B, Zhang JF, Xu HY, Hou LX, Wang YH, Zhang Y, Wang C. 2013.
Analysis of organic acid contents in wine grape from different cultivars.
Food Sci 34:223–8.
Cherrington C, Hinton M, Mead G, Chopra I. 1991. Organic acids:
chemistry, antibacterial activity and practical applications. Adv Microb
Physiol 32:87–108.
De Dios Lozano J, Ju´
arez-Flores BI, Pinos-Rodr´
ıguez JM, Aguirte-Rivera J,
Alvarez-Fuentez G. 2012. Supplementary effects of vinegar on body weight
and blood metabolites in healthy rats fed conventional diets and obese rats
fed high-caloric diets. J Med Plants Res 6:4135–41.
Dickschat JS, Wickel S, Bolten CJ, Nawrath T, Schulz S, Wittmann C. 2010.
Pyrazine biosynthesis in corynebacterium glutamicum. Eur J Org Chem
2010:2687–95.
Ebihara K, Nakajima A. 1988. Effect of acetic acid and vinegar on blood
glucose and insulin responses to orally administered sucrose and starch.
Agric Biol Chem 52:1311–2.
Entani E, Asai M, Tsujihata S, Tsukamoto Y, Ohta M. 1998. Antibacterial
action of vinegar against food-borne pathogenic bacteria including
Escherichia coli O157:H7. J Food Prot 61:953–9.
Fan J, Zhang Y, Chang X, Zhang B, Jiang D, Saito M, Li Z. 2009.
Antithrombotic and fibrinolytic activities of methanolic extract of aged
sorghum vinegar. J Agric Food Chem 57:8683–7.
Fushimi T, Sato Y. 2007. Effect of acetic acid feeding on the circadian
changes in glycogen and metabolites of glucose and lipid in liver and skeletal
muscle of rats. Br J Nutr 94:714–9.
Fushimi T, Suruga K, Oshima Y, Fukiharu M, Tsukamoto Y, Goda T. 2006.
Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed
a cholesterol-rich diet. Br J Nutr 95:916–24.
Garcı́a Parrilla MC, Heredia FJ, Troncoso AM. 1999. Sherry wine vinegars:
phenolic composition changes during aging. Food Res Int 32:433–40.
Gradiˇ
sar H, Pristovˇ
sek P, Plaper A, Jerala R. 2007. Green tea catechins
inhibit bacterial DNA gyrase by interaction with its ATP binding site. J
Med Chem 50:264–71.
Gu X, Zhao HL, Sui Y, Guan J, Chan JC, Tong PC. 2012. White r ice
vinegar improves pancreatic beta-cell function and fatty liver in
streptozotocin-induced diabetic rats. Acta Diabetol 49:185–91.
Guo Y, Liang J, Li MM, Zhao ZY. 2012. Determination of organic acids in
apple fruits by HPLC. Food Sci 33:227–30.
Hattori M, Kondo T, Kishi M, Yamagami K. 2010. A single oral
administration of acetic acid increased energy expenditure in C57BL/6J
mice. Biosci Biotechnol Biochem 74:2158–9.
He ZY, Ao ZH, Wu J. 2004. Study on the mensuration of
tetramethylpyrazine in Zhenjiang vinegar and its generant mechanism.
China Condiment 2:36–9.
Hindi NK. 2013. In vitro antibacterial activity of aquatic garlic extract, apple
vinegar and apple vinegar-garlic extract combination. Am J Phytomed Clin
Ther 1:42–51.
Hirshfield IN, Terzulli S, O’Byrne C. 2003. Weak organic acids: a panoply of
effects on bacteria. Sci Prog 86:245–69.
Hlebowicz J, Darwiche G, Bjorgell O, Almer LO. 2007. Effect of apple cider
vinegar on delayed gastric emptying in patients with type 1 diabetes
mellitus: a pilot study. BMC Gastroenterol 7:46.
Iizuka M, Tani M, Kishimoto Y, Saita E, Toyozaki M, Kondo K. 2010.
Inhibitory effects of balsamic vinegar on LDL oxidation and lipid
accumulation in THP-1 macrophages. J Nutr Sci Vitaminol 56:421–7.
Inagaki S, Morimura S, Gondo K, Tang Y, Akutagawa H, Kida K. 2007.
Isolation of tryptophol as an apoptosis-inducing component of vinegar
produced from boiled extract of black soybean in human monoblastic
leukemia U937 cells. Biosci Biotechnol Biochem 71:371–9.
Jeong CH, Choi GN, Kim JH, Kwak JH, Kang ST, Choi SG, Heo HJ. 2009.
In vitro antioxidant properties and phenolic composition of Korean
commercial vinegars. Food Sci Biotechnol 18:1258–62.
Johnston CS, Buller AJ. 2005. Vinegar and peanut products as
complementary foods to reduce postprandial glycemia. J Am Diet Assoc
105:1939–42.
Johnston CS, Steplewska I, Long CA, Harris LN, Ryals RH. 2010.
Examination of the antiglycemic properties of vinegar in healthy adults.
Ann Nutr Metab 56:74–79.
Johnston CS, White AM, Kent SM. 2009. Preliminary evidence that regular
vinegar ingestion favorably influences hemoglobin A1c values in individuals
with type 2 diabetes mellitus. Diabetes Res Clin Pract 84:e15–7.
Jung HH, Cho SD, Yoo CK, Lim HH, Chae SW. 2002. Vinegar treatment
in the management of granular myringitis. J Laryngol Otol 116:176–80.
Kadas Z, Akdemir Evrendilek G, Heper G. 2014. The metabolic effects of
hawthorn vinegar in patients with high cardiovascular risk group. J Food
Nutr Res 2:539–45.
KishiM,FukayaM,TsukamotoY,NagasawaT,TakehanaK,NishizawaN.
1999. Enhancing effect of dietary vinegar on the intestinal absorption of
calcium in ovariectomized rats. Biosci Biotechnol Biochem 63:905–10.
Kondo T, Kishi M, Fushimi T, Kaga T. 2009a. Acetic acid upregulates the
expression of genes for fatty acid oxidation enzymes in liver to suppress
body fat accumulation. J Agric Food Chem 57:5982–6.
C2016 Institute of Food Technologists®Vol.00,2016 rComprehensiveReviewsinFoodScience and Food Safety 13
Vinegar functions on health . . .
Kondo T, Kishi M, Fushimi T, Ugajin S, Kaga T. 2009b. Vinegar intake
reduces body weight, body fat mass, and serum triglyceride levels in obese
Japanese subjects. Biosci Biotechnol Biochem 73:1837–43.
Kosuge T, Kamiya H. 1962. Discovery of a pyrazine in a natural product:
tetramethylpyrazine from cultures of a strain of Bacillus subtilis.Nature
193:776.
Kosuge T, Zenda H, Tsuji K, Yamamoto T, Nar ita H. 1971. Studies on
flavor components of foodstuffs, part I: distribution of tetramethylpyrazine
in fermented foodstuffs. Agr ic Biol Chem 35:693–6.
Kyrø C, Zamora-Ros R, Scalbert A, Tjønneland A, Dossus L, Johansen C,
Bidstrup PE, Weiderpass E, Christensen J, Ward H. 2015. Pre-diagnostic
polyphenol intake and breast cancer survival: the European prospective
investigation into cancer and nutrition (EPIC) cohort. Breast Cancer Res
Treat 154:389–401.
Leeman M, Ostman E, Bjorck I. 2005. Vinegar dressing and cold storage of
potatoes lowers postprandial glycaemic and insulinaemic responses in
healthy subjects. Eur J Clin Nutr 59:1266–71.
Li B, Li ZX, Ying W, Zhang XL, Wu RQ, Fan YL, Bu LQ. 2009. Study on
the effects of brans and aspergillus niger about corn vinegar on reducing
obesity and blood lipids in rat. J Northwest A & F Uni (Nat Sci Ed)
37:194–8.
Li XJ, Wang XY, Yuan J, Lu M, Wang RH, Quan ZJ. 2013. The
determination and comparison of phenolics in apple vinegar, persimmon
vinegar and kiwifruit vinegar. Food Ferment Ind 39:186–90.
Liljeberg H, Bj¨
orck I. 1998. Delayed gastric emptying rate may explain
improved glycaemia in healthy subjects to a starchy meal with added
vinegar. Eur J Clin Nutr 52:368–71.
Lin HC, Doty JE, Reedy TJ, Meyer JH. 1990. Inhibition of gastric emptying
by acids depends on pH, titratable acidity, and length of intestine exposed to
acid. Am J Physiol Gastrointest Liver Physiol 259:G1025–30.
Liu L, Han YW, Wang N, Zhao L, Kou X, Li ZX. 2015. Effect of purple
sweet potato vinegar on hepatoprotective of acute liver injury and
mass-reducing, hypolipidemic in mice. Acta Agric Boreali-Occident Sin
24:28–33.
Liu L, Yang X. 2015. Hypolipidemic and antioxidant effects of freeze-dried
powder of Shanxi mature vinegar in hyperlipidaemic mice. Food Sci
36:141–51.
Lu PJ, Zhou YZ. 2002. Anti-fatigue function of Hengshun vinegar capsules.
China Condiment 10:8–13.
Ma TJ, Xia F, Jia CX. 2010. The influence of bitter buckwheat vinegar in
blood glucose of diabetic model mice. J Chin Cereals Oils Assoc 25:42–8.
Matsui T, Ebuchi S, Fukui K, Matsugano K, Terahara N, Matsumoto K.
2014. Caffeoylsophorose, a new natural α-glucosidase inhibitor, from red
vinegar by fermented purple-fleshed sweet potato. Biosci Biotechnol
Biochem 68:2239–46.
McLaggan D, Naprstek J, Buurman ET, Epstein W. 1994. Interdependence
of K+and glutamate accumulation during osmotic adaptation of Escherichia
coli. J Biol Chem 269:1911–7.
Mimura A, Suzuki Y, Toshima Y, Yazaki S-I, Ohtsuki T, Ui S, Hyodoh F.
2004. Induction of apoptosis in human leukemia cells by naturally fermented
sugar cane vinegar (kibizu) of Amami Ohshima Island. BioFactors 22:93–7.
Mitrou P, Raptis AE, Lambadiari V, Boutati E, Petsiou E, Spanoudi F,
Papakonstantinou E, Maratou E, Economopoulos T, Dimitriadis G. 2010.
Vinegar decreases postprandial hyperglycemia in patients with type 1
diabetes. Diabetes Care 33:e27.
Moon YJ, Cha YS. 2008. Effects of persimmon-vinegar on lipid metabolism
and alcohol clearance in chronic alcohol-fed rats. J Med Food 11:38–45.
Nakamura K, Ogasawara Y, Endou K, Fujimori S, Koyama M, Akano H.
2010. Phenolic compounds responsible for the superoxide dismutase-like
activity in high-Brix apple vinegar. J Agric Food Chem 58:10124–32.
Nanda K, Miyoshi N, Nakamura Y, Shimoji Y, Tamura Y, Nishikawa Y,
Uenakai K, Kohno H, Tanaka T. 2004. Extract of vinegar "Kurosu" from
unpolished rice inhibits the proliferation of human cancer cells. J Exp Clin
Cancer Res 23:69–76.
Nishidai S, Nakamura Y, Torikai K, Yamamoto M, Ishihara N, Mori H,
Ohigashi H. 2000. Kurosu, a traditional vinegar produced from unpolished
rice, suppresses lipid peroxidation in vitro and in mouse skin. Biosci
Biotechnol Biochem 64:1909–14.
Ochoa-Zarzosa A, Villarreal-Fern´
andez E, Cano-Camacho H, L´
opez-Meza
JE. 2009. Sodium butyrate inhibits Staphylococcus aureus internalization in
bovine mammary epithelial cells and induces the expression of antimicrobial
peptide genes. Microb Pathog 47:1–7.
Ogawa N, Satsu H, Watanabe H, Fukaya M, Tsukamoto Y, Miyamoto Y,
Shimizu M. 2000. Acetic acid suppresses the increase in disaccharidase
activity that occurs during culture of caco-2 cells. J Nutr 130:507–
13.
Ostman E, Granfeldt Y, Persson L, Bjorck I. 2005. Vinegar supplementation
lowers glucose and insulin responses and increases satiety after a bread meal
in healthy subjects. Eur J Clin Nutr 59:983–8.
Pazuch CM, Siepmann FB, Canan C, Colla E. 2015. Vinegar: functional
aspects. Cientifica 43:302–8.
Peng YT, Chen TY, Chen MC, Lin E, Lin H. 2014. Resveratrol regulates
phospho-serine 81 androgen receptor and its stability to inhibit growth of
prostate cancer cells. Cancer Res 74:2121.
Perron NR, Brumaghim JL. 2009. A review of the antioxidant mechanisms
of polyphenol compounds related to iron binding. Cell Biochem Biophys
53:75–100.
Petsiou EI, Mitrou PI, Raptis SA, Dimitriadis GD. 2014. Effect and
mechanisms of action of vinegar on glucose metabolism, lipid profile, and
body weight. Nutr Rev 72:651–61.
Plessi M, Bertelli D, Miglietta F. 2006. Extraction and identification by
GC-MS of phenolic acids in traditional balsamic vinegar from Modena. J
Food Compost Anal 19:49–54.
Ren Z, Ma J, Zhang P, Luo A, Zhang S, Kong L, Qian C. 2012. The effect
of ligustrazine on L-type calcium current, calcium transient and contractility
in rabbit ventricular myocytes. J Ethnopharmacol 144:555–661.
Rice-Evans CA, Miller NJ, Paganga G. 1996. Structure-antioxidant activity
relationships of flavonoids and phenolic acids. Free Radical Biol Med
20:933–56.
Rizz GP. 1972. Mechanistic study of alkylpyrazine formation in model
systems. J Agric Food Chem 20:1081–5.
Rodriguez MR, Oderiz MV, Her nandez JL, Lozano JS. 1992.
Determination of vitamin C and organic acids in various fruits by HPLC. J
Chromatogr Sci 30:433–7.
Roe AJ, McLaggan D, Davidson I, O’Byrne C, Booth IR. 1998.
Perturbation of anion balance during inhibition of growth of Escherichia coli
by weak acids. J Bacteriol 180:767–72.
Rufian-Henares JA, de la Cueva SP. 2009. Antimicrobial activity of coffee
melanoidins a study of their metal-chelating properties. J Agric Food Chem
57:432–8.
Ruri´
an-Henares JA, Morales FJ. 2008. Antimicrobial activity of melanoidins
against Escherichia coli is mediated by a membrane-damage mechanism. J
Agric Food Chem 56:2357–62.
Sakakibara S, Murakami R, Takahashi M, Fushimi T, Murohara T, Kishi M,
Kajimoto Y, Kitakaze M, Kaga T. 2010. Vinegar intake enhances
flow-mediated vasodilatation via upregulation of endothelial nitric oxide
synthase activity. Biosci Biotechnol Biochem 74:1055–61.
Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T. 2006.
Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic
KK-A(y) mice. Biochem Biophys Res Commun 344:597–604.
Sang S, Buckley B, Ho C-T, Yang CS. 2007. Autoxidative quinone
formation in vitro and metabolite formation in vivo from tea polyphenol
(–)-epigallocatechin-3-gallate: studied by real-time mass spectrometry
combined with tandem mass ion mapping. Free Radical Biol Med
43:362–71.
Schaefer S, Baum M, Eisenbrand G, Dietrich H, Will F, Janzowski C. 2006.
Polyphenolic apple juice extracts and their major constituents reduce
oxidative damage in human colon cell lines. Mol Nutr Food Res 50:24–
33.
Seki T, Morimura S, Shigematsu T, Maeda H, Kida K. 2004. Antitumor
activity of rice-shochu post-distillation slurry and vinegar produced from
the post-distillation slurry via oral administration in a mouse model.
BioFactors 22:103–5.
Sengun IY, Karapinar M. 2004. Effectiveness of lemon juice, vinegar and
their mixture in the elimination of Salmonella typhimurium on carrots (Daucus
carota L.). Int J Food Microbiol 96:301–5.
Setorki M, Asgary S, Eidi A, Rohani A, Khazaei M. 2010. Acute effects of
vinegar intake on some biochemical risk factors of atherosclerosis in
hypercholesterolemic rabbits. Lipids Health Dis 9:10.
Shimoji Y, Kohno H, Nanda K, Nishikawa Y, Ohigashi H, Uenakai K,
Tanaka T. 2004. Extract of Kurosu, a vinegar from unpolished rice, inhibits
azoxymethane-induced colon carcinogenesis in male F344 rats. Nutr
Cancer 49:170–3.
14 ComprehensiveReviews in Food Science and Food Safety rVol. 00, 2016 C2016 Institute of Food Technologists®
Vinegar functions on health . . .
Shimoji Y, Nanda K, Nishikawa Y, Hayashi R, Ohigashi H. 2003. Extract of
vinegar “Kurosu” from unpolished rice inhibits the development of colonic
aberrant crypt foci induced by. J Exp Clin Cancer Res 22:591–7.
Shimoji Y, Tamura Y, Nakamura Y, Nanda K, Nishidai S, Nishikawa Y,
Ishihara N, Uenakai K, Ohigashi H. 2002. Isolation and identification of
DPPH radical scavenging compounds in Kurosu (Japanese unpolished rice
vinegar). J Agric Food Chem 50:6501–3.
Shishehbor F, Mansoori A, Sarkaki A, Jalali M, Latifi S. 2008. Apple cider
vinegar attenuates lipid profile in normal and diabetic rats. Pak J Biol Sci
11:2634–8.
Shukla Y, Singh R. 2011. Resveratrol and cellular mechanisms of cancer
prevention. Ann N Y Acad Sci 1215:1–8.
Sirk TW, Brown EF, Sum AK, Friedman M. 2008. Molecular dynamics
study on the biophysical interactions of seven green tea catechins with lipid
bilayers of cell membranes. J Agric Food Chem 56:7750–8.
Solieri L, Giudici P. 2009. Vinegars of the world. Milan, Italy: Springer.
Soltan SS, Shehata M. 2012. Antidiabetic and hypocholesrolemic: effect of
different types of vinegar in rats. Life Sci J 9:2141–51.
Sun X, Hu M, Henrik M, Evans HS, Dai D, Duan W, Lu J. 2003. Risk
factors for oesophageal cancer in Linzhou, China: a case-control study.
Asian Pac J Cancer Prev 4:119–24.
Tagliazucchi D, Verzelloni E, Conte A. 2007. Antioxidant properties of
traditional balsamic vinegar and boiled must model systems. Eur Food Res
Technol 227:835–43.
Tagliazucchi D, Verzelloni E, Conte A. 2010. Contribution of melanoidins
to the antioxidant activity of traditional balsamic vinegar during aging. J
Food Biochem 34:1061–78.
Taguri T, Tanaka T, Kouno I. 2006. Antibacterial spectrum of plant
polyphenols and extracts depending upon hydroxyphenyl structure. Biol
Pharm Bull 29:2226–35.
Verzelloni E, Tagliazucchi D, Conte A. 2007. Relationship between the
antioxidant properties and the phenolic and flavonoid content in traditional
balsamic vinegar. Food Chem 105:564–71.
Verzelloni E, Tagliazucchi D, Conte A. 2010. From balsamic to healthy:
traditional balsamic vinegar melanoidins inhibit lipid peroxidation
during simulated gastric digestion of meat. Food Chem Toxicol 48:2097–
102.
Wang HY, Qian H, Yao WR. 2011. Melanoidins produced by the Maillard
reaction: structure and biological activity. Food Chem 128:573–84.
Wang LS, Guo Q, Han J, Zhang YF, Chen XJ. 2009. Pharmacokinetics of
ligustrazine in blood, brain, and liver of mice. Chin Tradit Herb Drugs
40:935–8.
Wei ZP, Li ZX, Yu XZ, Liu ZM, Cui XY, Jin J. 2005. Effect of mulberry
vinegar on reducing obesity of animals. China Brewing 12:5–7.
White AM, Johnston CS. 2007. Vinegar ingestion at bedtime moderates
waking glucose concentrations in adults with well-controlled type 2
diabetes. Diabetes Care 30:2814–5.
Wu D, Kimura F, Takashima A, Shimizu Y, Takebayashi A, Kita N, Zhang
G, Murakami T. 2013. Intake of vinegar beverage is associated with
restoration of ovulatory function in women with polycystic ovary
syndrome. Tohoku J Exp Med 230:17–23.
Xu Q, Ao Z, Tao W. 2003. Progress in vinegar function study. China
Condiment 12:11–23.
Xu QP, Tao WY, Ao ZH. 2005. Antioxidation effects of vinegar on ageing
accelerating model mice. Food Sci 26:205–7.
Xu QP. 2008. The vinegar production technology. Beijin, China: Chemical
Industry Press.
Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M, Hiemori
M, Tsuji H. 2014. Improvement of obesity and glucose tolerance by acetate
in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
Biosci Biotechnol Biochem 71:1236–43.
YamashitaH,MarutaH,JozukaM,KimuraR,IwabuchiH,YamatoM,
Saito T, Fujisawa K, Takahashi Y, Kimoto M, Hiemor i M, Tsuji H. 2009.
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 73:570–6.
Yang L, Wang X, Yang X. 2014. Possible antioxidant mechanism of
melanoidins extract from Shanxi aged vinegar in mitophagy-dependent and
mitophagy-independent pathways. J Agric Food Chem 62:8616–22.
Yoda Y, Hu ZQ, Zhao WH, Shimamura T. 2004. Different susceptibilities
of Staphylococcus and Gram-negative rods to epigallocatechin gallate. J
Infect Chemother 10:55–8.
Yuan R, Ao ZH, Ding HL, Shen CH, HUang ZG, Ren JB, Fu X. 2011.
Measuring on the fatty acids and low molecular weight organic acids from
sorghum by gas chromatography. Liquor Making 38:42–3.
Zamora-Ros R, Knaze V, Rothwell JA, H´
emon B, Moskal A, Overvad K,
Tjønneland A, Kyrø C, Fagherazzi G, Boutron-Ruault M-C. 2015. Dietary
polyphenol intake in Europe: the European prospective investigation into
cancer and nutrition (EPIC) study. Eur J Nutr 1–17.
Zhang J, Tian Z, Wang J, Wang A. 2011. Advances in antimicrobial
molecular mechanism of organic acids. Acta Vet Zootech Sin (Chin J Anim
Vet Sci) 42:323-8.
Zhang L, Li Z, Du S. 2007. Study on the effects of mulberry vinegar on
weight losing and antifatigue in rat. J Northwest Sci-Tech Uni Agr ic For
35:227–30.
Zhou X, Salganicoff L, Sevy R. 1985. The pharmacological effect of
ligustrazine on human platelets. Acta Pharm Sin 20:334–9.
C2016 Institute of Food Technologists®Vol.00,2016 rComprehensiveReviewsinFoodScience and Food Safety 15
