Tohoku J. Exp. Med.

, 2013, 230, 17-23 Vinegar for Polycystic Ovary Syndrome 17

Intake of Vinegar Beverage Is Associated with Restoration of

Ovulatory Function in Women with Polycystic Ovary Syndrome
Di Wu,1,2 Fuminori Kimura,1 Akiko Takashima,1 Yoshihiko Shimizu,1
Akie Takebayashi,1 Nobuyuki Kita,1 GuangMei Zhang2 and
Takashi Murakami1
1
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Japan
2
Department of Obstetrics and Gynecology, 1st Affiliated Hospital, Harbin Medical University, Harbin, China

Polycystic ovary syndrome (PCOS) is one of major causes of irregular menstruation. It is defined as a
condition involving the combination of hyperandrogenism and chronic oligomenorrhea or anovulation, and
is thought to have a variety of etiologies. Insulin resistance (impaired insulin sensitivity) has been
suggested to be one of the etiologies of PCOS. PCOS patients often need to take medication to treat
anovulation and infertility. Therefore, it would be beneficial to patients if simple non-pharmacological
treatments can be developed. Recently the efficacy of vinegar to improve insulin resistance has been
reported. To study the effect of vinegar on metabolic and hormonal indices and ovulatory function in PCOS,
seven patients seeking a non-pharmacological treatment for PCOS took a beverage containing 15 g of
apple vinegar daily for 90 to 110 days. Ovulation, the menstrual interval, fasting serum glucose level,
fasting serum insulin level, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone
were compared before and after intake of the vinegar beverage. Intake of the vinegar beverage resulted in
a decrease of the homeostasis model assessment insulin resistance index (HOMA-R) in six patients, as
well as a decrease of the LH/FSH ratio in five of seven patients. Ovulatory menstruation was observed
within 40 day in four of seven patients. These findings suggest the possibility of vinegar to restore ovulatory
function through improving insulin sensitivity in PCOS patients, thus, avoiding pharmacological treatment.
Intake of vinegar might reduce medical cost and treatment time for insulin resistance, anovulation, and
infertility in patients with PCOS.

Keywords : acetic acid; insulin resistance; metformin; polycystic ovary syndrome; vinegar
Tohoku J. Exp. Med., 2013 May, 230 (1), 17-23.  © 2013 Tohoku University Medical Press

mechanisms underlying insulin resistance and reproductive

Introduction anomalies in women with PCOS have not been clearly
Polycystic ovary syndrome (PCOS) is one of the major defined (Falcone et al. 1990; Sharp et al. 1991; Dewailly
causes of irregular menstruation; it affects 4-8% of women and Cortet-Rudelli 1992). The heterogeneity of PCOS
of reproductive age (Knochenhauer et al. 1998; Diamanti- makes it difficult to elucidate the mechanism. However,
Kandarakis et al. 1999; Agrawal et al. 2004; Carmina and insulin resistance has been reported to be associated with a
Azziz 2006). It is defined as a condition involving the com- greater risk of anovulation in women with PCOS (Palomba
bination of hyperandrogenism and chronic oligomenorrhea et al. 2009a, 2009b). Therefore, this metabolic abnormality
or anovulation, and is thought to have a variety of etiologies might be a key to ovulatory dysfunction in a portion of
(Carmina and Azziz 2006; Fauser et al. 2012). Recently, women with PCOS. To date, the optimal long-term man-
Insulin resistance (impaired insulin sensitivity) has been agement of PCOS has not been determined. One of the
suggested to be one of the features of PCOS. In addition, main aims of treatment for PCOS is to restore ovulation so
some genetic factors have been reported to contribute to that these women can conceive. Accordingly, insulin sensi-
both reproductive and metabolic abnormalities in PCOS. tizers have been used to promote ovulation and fertility in
(Legro and Strauss 2002; Doi et al. 2005). However, the women with PCOS (Moghetti et al. 2000; Onalan et al.

Received February 14, 2013; revised and accepted April 11, 2013. Published online May 11, 2013; doi: 10.1620/tjem.230.17
Correspondence: Fuminori Kimura, M.D., Ph.D., Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta,
Tsukinowa-cho, Otsu 520-2192, Japan.
e-mail: [email protected]
GuangMei Zhang, M.D., Ph.D., Department of Obstetrics and Gynecology, 1st Affiliated Hospital, Harbin Medical University, Harbin
150006, China.
e-mail: [email protected]

17
18 D. Wu et al.

2005; Eisenhardt et al. 2006). Women with a history of glucose intolerance (including gestational
The insulin sensitizer employed most often for the diabetes) or type 2 diabetes were also excluded. Since acetic acid has
treatment of PCOS is metformin (dimethylbiguanide). a strong, distinct odor, the participants can distinguish whether the
Metformin is administered orally to lower the blood glu- beverage includes acetic acid. Therefore, we could not design a case-
cose level in patients with type 2 diabetes (Buse 1999; Bosi control study using a different beverage that does not contain vinegar.
Prior to starting vinegar intake, blood tests including LH, FSH, tes-
2009), since it enhances the insulin sensitivity of both the
tosterone, fasting insulin, and fasting glucose were drawn from day 3
liver and the peripheral tissues (Phielix et al. 2011). In
through day 5 of the menstrual cycle or at the quiescent phase when
addition, metformin was administered to 40 women with
the largest follicle was < 10 mm in diameter, if that phase persisted
PCOS to increase insulin sensitivity and reduce the sequelae for more than 30 days. The blood test was drawn on the morning
of hyperinsulinemia, with ovulation being achieved in 27 after fasting for at least eight hours. The homeostasis model assess-
patients (Palomba et al. 2009a). Accordingly, metformin is ment of insulin resistance index (HOMA-R) was calculated by the
commonly used to achieve ovulation in the patients with formula: fasting serum glucose level × fasting serum insulin levels ÷
PCOS. 405. Subsequently, 100 ml of a beverage containing 15 g of apple
Vinegar is a common cooking ingredient. The most vinegar (MAINZ, Mizkan Co., Ltd., Handa, Japan) was ingested
important component of vinegar is acetic acid together with immediately after dinner daily for 90 to 110 days. The ingredient
small amounts of vitamins, mineral salts, and amino acids. composition of the apple vinegar beverage is shown in Table 1. Basal
Although vinegar is mainly used for cooking, it is consid- body temperature (BBT) was checked and recorded in a similar note-
ered to have several effects such as antibacterial (Entani et book by each patient. In addition, each patient recorded the onset of
al. 1998; Sengun and Karapinar 2004), cardiovascular pro- menstruation and whether she consumed the vinegar beverage. All
tection (Kondo et al. 2001; Honsho et al. 2005), and antitu- patients visited our hospital at least every 28 days and were examined
mor properties (Mimura et al. 2004; Nanda et al. 2004). by trans-vaginal or trans-abdominal ultrasonography at every visit.
The BBT records were checked by doctors at every visit, and ovula-
Recent studies have shown that intake of vinegar with or
tion was diagnosed by two doctors individually. When the formation
after a meal can reduce the post-prandial glucose level
of a corpus luteum was confirmed by ultrasonography or the high
(Johnston et al. 2004; Östman et al. 2005). Östman et al.
phase, diagnosed when the BBT was at least 0.4°C higher than in the
(2005) reported that ingesting a meal with vinegar reduced low phase, persisted for more than 10 days, the patient was defined as
the postprandial responses of blood glucose and insulin in having ovulated. The interval between menstruations was calculated
12 non-diabetic healthy volunteers. Although there was no by reviewing the BBT record. On day 3 to day 5 of the menstrual
significant effect of vinegar on postprandial glucose levels cycle, after ingestion of the beverage for 90 to 110 days, blood tests
in type 2 diabetic patients, vinegar was found to improve were redrawn. When ovulation was not confirmed after taking the
insulin sensitivity during the initial 30-minute period after beverage for 90 days, blood tests were drawn and progestins were
meals in subjects with insulin resistance (Johnston et al. given to induce withdrawal bleeding. Because the data was not nor-
2004). These reports led to the hypothesis that vinegar mally distributed, paired Wilcoxon nonparametric test was used to
might improve insulin sensitivity in women with PCOS compare the results before versus after taking the apple vinegar bev-
who have normal insulin sensitivity or insulin resistance. erage for at least 90 days.
Because patients easily consume vinegar, it might be useful
as a non-pharmacological treatment for PCOS. In this Results
study, therefore we assessed the influence of vinegar on The ingredient composition of 100 ml of the beverage
hormonal indices and ovulation in women with PCOS. Our contains 15 g of apple vinegar (Table 1). The apple vinegar
results suggest that vinegar intake restored ovulatory men-
struation, together with a decrease of the LH/FSH ratio and
improvement of insulin resistance, in women with PCOS. Table 1. Ingredient composition of the apple vinegar beverage.

Ingredient composition Weight

Materials and Methods total weight 102 g
The present study was approved by the Institutional Review acetic acid 750 mg
Board of Shiga University of Medical Science. The purpose and pro- water 96.0 g
cedures were carefully explained to all of the participants and written carbohydrates 3.6 g
informed consent was obtained. Seven women aged 21 through 40
ash 1.0 g
years old were enrolled. PCOS was diagnosed, according to the crite-
sodium 4.0 mg
ria of the Japanese Society of Obstetrics and Gynecology by the pres-
ence of the following three features: 1) oligomenorrhea or anovula- potassium 140.0 mg
tion, that is, irregular menstruation; 2) polycystic ovaries, defined as calcium 60.0 mg
the presence of more than 10 antral follicles in a ovary; and 3) clinical Vitamin C 55.0 mg
and/or biochemical evidence of hyperandrogenism, or biochemical
The ingredient composition of 100 ml of the beverage
evidence of both high LH and normal FSH after exclusion of related containing 15 g of apple vinegar is shown. The apple
disorders. Exclusion criteria include congenital adrenal hyperplasia, vinegar contains 5% (weight/weight) of acetic acid. There-
Cushing’s syndrome, hyperprolactinemia, and thyroid dysfunction. fore, 100 ml of the beverage contains 750 mg of acetic acid.
 Vinegar for Polycystic Ovary Syndrome 19

Table 2. Patient profiles.

Patient Height Weight Body Mass Index
Age Gravidity Parity Menstrual Status
No (cm) (kg) (BMI)

1 26 0 0 157  85 34.5 oligomenorrhea (> 45-day interval)

2 23 0 0 169 105 36.8 amenorrhea
3 32 0 0 167  68 24.4 oligomenorrhea (> 50-day interval)
4 30 0 0 158  51 20.4 anovulatory cycle
5 27 0 0 148  43 19.6 anovulatory cycle
6 40 0 0 159  60 23.7 amenorrhea
7 30 2 1 153  62 26.5 amenorrhea
The age, gravidity, parity, body weight, height, body mass index and menstrual cycle status of the patients are shown. Their age
was between 23 and 40 years. Patients 1 and 2 were defined as obese and patient 7 was overweight. Two of the seven patients were
oligomenorrheic, three were amenorrheic, and two had anovulatory menstrual cycles. Oligomenorrhea and amenorrhea are defined
when the menstrual intervals are > 40 days and > 90 days, respectively.

contains 5% (weight/weight) of acetic acid. Therefore, 100 deteriorated after she ceased ingestion of apple vinegar for
ml of the beverage contains 750 mg of acetic acid. The four months (Table 3). Furthermore, patient 3 had been
profile of the patients, including age, gravidity, parity, body infertile for two years. She ingested the vinegar beverage
weight, height, body mass index, and menstrual status for another two months after regular intake for 90 days and
before intake of the apple vinegar, is shown in Table 2. became pregnant without any other treatment. These find-
Based on the body mass index, two of the seven patients ings also suggest that vinegar has a role in the restoration of
were defined as obese and one was overweight. There were ovulatory function and the promotion of fecundity.
two patients with oligomenorrhea, three patients with
amenorrhea, and two patients with anovulatory menstrual Discussion
cycles. After the intake of apple vinegar, ovulatory men- For more than 2000 years, vinegar has been used to
struation was observed within 40 days in four of the seven season and preserve foods, heal wounds, treat infections
patients (patients 1 to 4), including both of the obese (Entani et al. 1998; Sengun and Karapinar 2004), prevent
patients (patient 1 and 2). Ovulatory menstruation took cardiovascular disease (Kondo et al. 2001; Honsho et al.
longer than 40 days in two of the patients (patients 5 and 6). 2005), and suppress tumor formation (Mimura et al. 2004;
No ovulatory menstruation was observed for 90 days in one Nanda et al. 2004). It has been suggested that vinegar
patient (patient 7), who was treated by progestins. reduces the glucose response to a carbohydrate load in sub-
HOMA-R was obtained for only six of the seven patients. jects with insulin resistance and healthy adults (Carol et al.
When compared to the level before vinegar intake, the 2004). Johnston and colleagues (2004) reported that sub-
HOMA-R decreased after intake of the beverage in all six jects with insulin resistance or type 2 diabetes took a vine-
of the patients; however, the difference was not significant gar beverage (20 g of vinegar, 40 g of water, and 1 tsp of
difference (Fig. 1a). The LH/FSH ratio decreased in five of saccharine) or placebo before meals (87 g of total carbohy-
the seven patients, including all four patients who resumed drate). In the insulin resistant subjects, ingestion of vinegar
ovulation within forty days (Fig. 1b). There was no change significantly reduced postprandial glycemia compared with
in the serum total testosterone level before and after taking placebo and improved postprandial insulin sensitivity by
the vinegar beverage (Fig. 1c). 34%. In the subjects with type 2 diabetes, vinegar ingestion
A typical patient with restored ovulation after the was less effective for reducing glycemia; however, the dif-
intake of the vinegar beverage (patient 1) is shown in Fig. 2 ference was not statistically significant. Despite that find-
and Table 3. The patient ingested two courses of the apple ing, vinegar ingestion reduced postprandial glucose level by
vinegar beverage. Before starting intake of the beverage, 19%; therefore, this negative outcome may have been due
she was oligomenorrheic with a menstrual interval that was to the study size or variations of the effect on the glucose
usually longer than 50 days. The menstruation interval concentration. In addition, Östman et al. (2005) demon-
became shorter during and just after intake of the beverage strated that acetic acid reduced postprandial serum glucose
in both the first and second courses and became longer levels and insulin levels in healthy subjects. These subjects
again after she ceased ingesting the vinegar beverage (Fig. took meals (50 g carbohydrate) alone or with 3 portions of
2). Moreover, the LF/FSH ratio and HOMA-R were a vinegar beverage containing 1.1, 1.4, or 1.7 g of acetic
improved at the end of both courses. However, if compared acid. All vinegar concentrations reduced postprandial gly-
the LH/FSH ratio and HOMA-R between the end of the cemia compared with placebo. These findings suggest that
first course on day 128 and before starting the second vinegar improves insulin sensitivity and regulates blood
course on day 292, the metabolic and hormonal status were glucose in healthy adults.
20 D. Wu et al.

Fig. 1. Metabolic and hormonal parameters before and after ingestion of the vinegar beverage.
Four patients (patients 1 to 4) showed improvement of their menstrual cycle and are indicated by unbroken lines, while
three (patients 5 to 7) without improvement are shown by dotted lines.
(a) Homeostasis model assessment of insulin resistance index (HOMA-R) before and after intake of the vinegar bever-
age. Patient 6 missed the blood test for HOMA-R. Thus, HOMA-R was analyzed only in six patients. HOMA-R was
decreased by vinegar intake in six patients; however, the difference was not statistically significant between before and
after vinegar intake (P = 0.23). (b) LH/FSH ratio before and after intake of the vinegar beverage. The LH/FSH ratio
decreased in five of seven patients, including all four with improvement; however, the difference was not statistically
significant between before and after vinegar ingestion (P = 0.23). (c) Serum total testosterone level before and after in-
take of the vinegar beverage. There was no change in the serum total testosterone level before and after intake of the
vinegar (P = 0.55).

Although it still remains unclear how vinegar alters the suggested that the mechanism was related to delayed gastric
glycemic response to a meal, several mechanisms have emptying as judged from lower paracetamol levels after the
been proposed. Some investigators have examined whether test meal with vinegar. Conversely, in rats fed experimental
delayed gastric emptying is related to the antiglycemic diets containing the indigestible marker polyethyleneglycol
effect of vinegar. Liljeberg and Björck (1998) reported that and various concentrations of acetic acid, dietary acetic acid
vinegar significantly reduced the postprandial glucose and did not alter gastric emptying, food intake, or glucose
insulin responses to a starchy meal in healthy subjects and absorption (Fushimi et al. 2001). Thus, the effect of vine-
 Vinegar for Polycystic Ovary Syndrome 21

Fig. 2. Clinical course of patient 1.

Patient 1 completed two courses of the vinegar beverage ingestion, shown as the lines with arrowheads (↕). Numbers
shown indicate dates counted from the start of the clinical study. Black boxes indicate menstrual periods, with the date
of onset of menstruation. The first course of the vinegar beverage ingestion started on day 37 and ended on day 127,
and the second course started on day 292 and ended on day 391. The patient’s blood was sampled on day 23 (just
before the first course of vinegar beverage ingestion), day 128 (the end of the first course of vinegar beverage ingestion),
day 292 (just before the second course of vinegar beverage ingestion) and day 385 (the end of the second course of vin-
egar beverage ingestion). Note that the menstrual interval became shorter during and just after intake of the vinegar
beverage; however, it became longer after vinegar intake ceased.

Table 3. HOMA-R, LH/FSH ratio, and serum testosterone level of patient 1.

The first course of vinegar ingestion The second course of vinegar ingestion

Day 23 Day 128 Day 292 Day 385

(Before vinegar) (After vinegar) (Before vinegar) (After vinegar)

HOMA-R 2.49 1.06 3.11 1.23

LH/FSH 0.93 0.34 1.42 0.22
Testosterone (ng/dl) 51 58 63 33

Patient 1 underwent the two courses of ingestion of the apple vinegar beverage. The patient’s blood was sampled on the indicated
time points: day 23 just before the first course of vinegar beverage ingestion, day 128 at the end of the first course, day 292 just before
the second course, and day 385 at the end of the second course (see Fig. 2). Comparing the values before and at the end of vinegar
ingestion in two courses, HOMA-R and the LH/FSH ratio were improved after vinegar ingestion. In contrast, both parameters were
deteriorated after vinegar ingestion was discontinued.

gar on gastric emptying is still controversial. metformin suppresses glucose-6-phospatase expression to

Another approach for investigating the effect of vine- increase the intracellular level of G6P and decrease serum
gar is to analyze the enzymes involved in glucose digestion glucose (Fushimi et al. 2001). G6P is utilized for glycolysis
or glucose metabolism. Ogawa et al. (2000) examined the and the pentose phosphate pathway or is converted glyco-
effects of acetic acid and other organic acids on disacchari- gen.
dase activity in CACO-2 human colon cancer cells. In addition, metformin has been reported to activate
Disaccharidases are glycoside hydrolases, which are 5′-AMP-activated protein kinase (AMPK), an enzyme that
enzymes that break down disaccharides into monosaccha- plays an important role in insulin signaling, whole body
rides, including sucrose, lactase, and maltase. They found energy balance, and the metabolism of glucose and fats
that acetic acid suppressed sucrose, lactase, and maltase (Towler and Hardie 2007). Sakakibara et al. (2006)
activity in a concentration- and time-dependent manner, revealed the efficacy of acetic acid on reducing fasting
while the other organic acids did not alter these enzyme plasma glucose level and hemoglobin A1c by giving mice
activities; they found that acetic acid did not alter de novo 0.3% acetic acid for 8 weeks. Acetic acid reduced the
synthesis of the sucrose-isomaltase complex at either the expression of genes involved in gluconeogenesis and lipo-
transcriptional or translational level. The investigators con- genesis, which is partially regulated by AMPK. They also
cluded that acetic acid’s suppressive effect probably occurs reported that sodium acetate, in the form of neutralized
during posttranslational processing of the enzyme complex. AcOH, directly activated AMPK and lowered the expres-
Vinegar has also been reported to increase the glucose- sion of genes such as for glucose-6-phosphatase
6-phosphate (G6P) concentration in skeletal muscle, just as (Sakakibara et al. 2006). These results indicate that the
22 D. Wu et al.

hypoglycemic effect of AcOH might be due to activation of tion in PCOS patients.

AMPK as well as the efficacy of metformin. There has been one report regarding adverse reactions
There have been no reports about a direct effect of vin- to vinegar (Carol and Cindy 2006). Aspiration of vinegar
egar or acetic acid on folliculogenesis and ovarian function; has been related to laryngospasm, resulting in subsequent
therefore, we could not determine how ovulatory function vasovagal syncope. Also, inflammation of the oropharynx
was restored in our PCOS patients by vinegar ingestion. and second-degree caustic injury of the esophagus and car-
However, we theorize that vinegar reduces insulin resis- dia were observed in a 39-year-old woman who drank 1
tance by activating AMPK and suppressing glucose-6- tablespoon of rice vinegar. Her symptom resolved sponta-
phosphatase in the skeletal muscles and peripheral tissues neously after several days (Chung 2002). The odor and
of our PCOS patients. That is, vinegar improved ovarian taste of vinegar are related to adverse effects; however,
function by regulating insulin resistance in the same way as these symptoms resolve spontaneously. Esophageal injury
metformin acts on PCOS. due to vinegar appears to be rare; however, it merits atten-
Our study suggests that vinegar may be effective for tion. Although chronic inflammation of the esophagus is a
obese PCOS patients and/or patients with PCOS and insulin cancer risk, vinegar is reported to be inversely associated
resistance. In both obese patients (patients 1 and 2), ovula- with the risk of cancer of the esophagus (Xibib et al. 2003).
tion was restored or the menstrual cycle was shortened. In These reports suggest that vinegar is safe at low concentra-
patients 1 through 3, who responded well to the vinegar tions. In our study, 100 ml of the apple vinegar beverage
beverage, HOMA-R was decreased by more than 50%. contained 750 mg of acetic acid and the sour taste was
These findings also suggest that vinegar acted through the reduced at this concentration. None of the patients com-
improvement of insulin resistance. plained about the taste in this study.
Velazquez et al. (1994) first reported the efficacy of Although the sample size of this study was small, it is
metformin on restoring menstrual cycles in amenorrheic hopefully sufficient to indicate the possibility of the inges-
women with PCOS. Subsequently, uncontrolled studies and tion of vinegar to improve insulin resistance, ovulatory
randomized, controlled trials have evaluated the efficacy of function, and menstrual regularity in patients with PCOS.
metformin for improvement of menstruation (Moghetti et Intake of vinegar might reduce medical cost and the time
al. 2000; Palomba et al. 2009b). The results obtained from needed to treat anovulation, infertility, and insulin resis-
several uncontrolled studies have indicated that metformin tance in patients with PCOS. To the best of our knowledge,
is effective for restoring the menstrual cycle in approxi- this is the first report on the efficacy of vinegar for PCOS.
mately 62% of oligomenorrheic women with PCOS Further studies are needed to confirm this efficacy.
(Palomba et al. 2009b). In a randomized, double-blind,
placebo-controlled study, the effect on menstrual irregulari- Acknowledgements
ties after six months of metformin treatment was assessed The authors thank the Central Clinical Laboratory of Shiga
in 23 PCOS patients (Moghetti et al. 2000). They showed University of Medical Science for serum analysis.
that metformin produced a significant improvement of the
menstrual cycle while no efficacy was observed for the pla- Conflict of Interest
cebo control and five women in the metformin group vs. We have no conflicting interest affecting the present study.
none in the placebo group had their menstrual pattern sub-
stantially improved during treatment (Moghetti et al. 2000). References
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