Consumer health benefits of habitual consumption of chlorogenic acid-enriched coffee: a large single-arm study

Abdominal obesity is considered a fundamental cause of metabolic syndrome. It has been reported that continuous consumption of chlorogenic acid, which is a major component of coffee polyphenols, reduces abdominal fat together with body weight in humans. Chlorogenic acid-enriched ready-to-drink coffee has been developed recently. The antiobesity function of chlorogenic acid-enriched coffee has been demonstrated in some clinical trials; however, the efficacy of this coffee in daily life, which is more relevant in terms of consumer health, remains unknown. This paper describes a large single-arm study of the acceptability and effectiveness of chlorogenic acid-enriched coffee in terms of weight loss. Participants received one free carton (30 cans) of chlorogenic acid-enriched coffee and were encouraged to consume one can each day, and record their weight and coffee consumption using a web-based weight-recording system. The chlorogenic acid-enriched coffee showed high consumer acceptability. The mean weight change at Week 12 was −1.06 kg (95% confidence interval: −0.96, −1.16). Weight loss was significantly greater in obese participants compared with those with normal body mass index (<25 kg/m2) in both men and women. Changes in weight at Week 12 showed a significant dose-response relationship (p<0.001, n=1659). The habitual consumption of chlorogenic acid-enriched coffee together with the use of a weight-recording system was effective for achieving weight loss in daily life. The popularity of drinking coffee across all ages suggests a potentially substantial impact from substituting one cup of coffee a day with chlorogenic acid-enriched coffee.

coffee was developed by Kao Corporation under the brand name Healthya™. It contains 270 mg chlorogenic acid per can (185 g) with reduced hydroxyhydroquinone. Regular coffee contains approximately 35-175 mg per cup [19]. Canned beverages, including soft drinks such as fruit juice, carbonated beverages, green tea and brewed coffee, are very popular in Japan [20], and can be easily purchased at many types of retailer and vending machines. Canned coffee has the second largest share of the soft drink market in Japan, after carbonated beverages [21]. A canned coffee product with an anti-obesity function is therefore an ideal product to support a population-based public health strategy [22].
The anti-obesity function of chlorogenic acidenriched coffee has been demonstrated in some clinical trials [17,18], therefore it has been approved as a food for specified health use (FOSHU) by the Consumer Affairs Agency, Government of Japan, as a part of product development. However, the efficacy of the coffee in daily life, which is more relevant in terms of consumer health, remains unknown. The purpose of this study was to assess the acceptability and effectiveness of chlorogenic acid-enriched coffee in terms of weight loss in daily life through a large single-arm study.

Test beverage
The test beverage is a canned coffee already on the Japanese retail market (Healthya coffee) which contains 185 g of brewed coffee without milk and sugar.
The coffee is brewed from roasted coffee beans using 2.5 times the volume of roasted coffee beans compared with a conventional brew of coffee, after which the oxidant components, including hydroxyhydroquinone, are removed by filtration. The canned coffee contains approximately 270 mg of chlorogenic acids, including 5-caffeoyl, 3-caffeoyle, 4-caffeoyle, 3-ferulyl, 4-ferulyl and 5-ferulyl quinic acids, and approximately 90 mg of caffeine. The coffee has 9 kcal (37.7 kJ) of energy composed of 0.5 g of protein, 0 g of fat and 1.9 g of carbohydrate per can. coffee across all ages suggests a potentially substantial impact from substituting one cup of coffee a day with chlorogenic acid-enriched coffee.

Introduction
Obesity is a serious health problem worldwide [1,2] and abdominal obesity is considered a fundamental cause of metabolic syndrome [3][4][5][6], which leads to insulin resistance and a reduction in insulin secretory function, resulting in the complications of hyperglycaemia, hypertension and hyperlipidaemia.
Abdominal obesity [7] is defined as an accumulation of abdominal body fat, which is determined by the balance between energy intake and expenditure [8].
In recent years, many people have struggled to manage this balance because of the increased availability of palatable and hedonic foods, such as high-sugar and/or high-fat foods [9], leading to a potential increase in the need for anti-obesity foods.
The prevalence of obesity is not high in the Japanese population compared with Europe or America [10].
However, a recent meta-analysis suggested that compared with Caucasians, a small decrease in insulin secretory function in East Asians can lead to a large decrease in the threshold level of insulin resistance, above which the onset of type 2 diabetes occurs [11]. East Asians including Japanese tend to be diagnosed with type 2 diabetes without severe obesity.
Chlorogenic acid is a major component of coffee polyphenols. Coffee enriched with chlorogenic acid and with reduced hydroxyhydroquinone, an oxidant component, has been studied. It was shown that its metabolites improved vascular endothelial function, and consequently it reduced blood pressure in rodents [12] and in humans [13,14]. Furthermore, consumption of chlorogenic acid increases fat utilization in rodents [15,16] and in humans [17]. Nagao et al. reported that the continuous consumption of chlorogenic acid-enriched coffee reduced body fat, particularly abdominal fat, together with body weight through increased fat utilization in humans [18].
Chlorogenic acid-enriched ready-to-drink (canned) Nutrafoods (2014) 13:103-111 could record health-related information such as pedometer count, body-fat percentage estimated by bioimpedance measurement, exercise activities and consumption of anti-obesity beverages other than the coffee to maintain their motivation for recording. However, these data were not analysed in the present study. During the 30-day period, participants were sent eight e-mails to remind them to drink the coffee and to record the parameters.

Participants
Participants were those participants who registered the date of receipt of the coffee. The following participants were excluded from the analysis: participants with particularly low or high weights (<40 kg or ≥140 kg for men, and <30 kg or ≥130 kg for women) [23], participants with a percentage weight change ≤−25% or ≥+25%, participants without baseline weight data and participants with no weight data other than baseline weight.
A flow chart of the data-gathering procedure is shown in Fig. 2. All participants agreed to the use of their data for academic studies through a web page on the online system.

Statistical analysis
The weight-recording system remained accessible after the end of the 30-day monitoring period and the daily records in the system were evaluated for a total of 12 weeks after Day 1. We defined the period from Day 1 to Day 28 as the 'ad libitum consumption period', and from Day 29 to Day 84 as the 'add-on consumption period'. Baseline weight was defined as the average weight on Days 1-3.
The weekly average was defined as the average weight for the subsequent 7-day periods. Where no weight data were available to calculate the weekly average, the data were considered as missing. Statistical analysis was carried out using the data set defined in Fig. 2.
Using all the available data, the probability of Web recording of behaviour (P REC ), conditional probabilities of Web recording with coffee consumption

Study design
Participants were recruited from the general population, securing a wide variety of Japanese consumers, using several marketing approaches, including poster advertisements in trains, flyers on shop shelves and banner advertising on the product's website. Over 50,000 participants enrolled on the designated website. All participants were provided with one free carton (30 cans) of chlorogenic acid-enriched coffee. Participants were asked to register the day they received the coffee by clicking a button on the web-based weight-recording system provided (Fig. 1). The date of receipt was considered as Day 1 of the 30-day official monitoring period.
Participants were asked to consume the chlorogenic acid-enriched coffee every day for 30 days and to record their weight and coffee consumption using the web-based weight-recording system. The system Nutrafoods (2014) 13:103-111 1 3  We analysed how these variables were mutually related using graphical modelling [24].
Statistical analysis was carried out using R statistical analysis software (Version 3.0.2) [25]. p values <0.05 were considered as significant in two-tailed statistical tests. Asymptotic confidence intervals (CI) were indicated as error bars.

Participation
The number of participants at the beginning of the  Obesity and the Japanese Government [27].

Dose-response relationship with weight loss
Consumption of more than 30 cans indicated that the participants had purchased more coffee themselves. The relationship between coffee consump-kg/m 2 is considered 'obese' according to the World Health Organization (WHO) [26], whereas these Nutrafoods (2014) 13:103-111  chlorogenic acid-enriched coffee was therefore assumed to be highly acceptable.
There was a significant dose-response relationship between coffee consumption and weight loss over 12 weeks (Fig. 5). The mean weight change at Week 12 was −1.62 kg in participants who consumed the coffee every day (71-84 cans in 84 days), which was similar to the weight loss of −1.5 kg observed in the earlier 12-week clinical trial [18]. We could not discriminate between the effects of chlorogenic acid and caffeine in terms of weight loss from the results of the present study. However, a placebo beverage used in an earlier study [18] was a caffeinated coffee test beverage, which allows us to infer that the chlorogenic acid was a major contributing factor.
The significantly greater partial correlation coefficient between P REC and P REC |P CONS compared with P REC and P REC |P WEIGH suggests that Web recording was elicited by coffee consumption, rather than by self-weighing in the ad libitum consumption period. However, coffee consumption and self-weighing tion and weight change is shown in Fig. 5. There was a significant dose-response relationship according to the Jonckheere trend test (p<0.001). Greater weight loss was observed with increased coffee con- Subject demographics for each dose group are presented in Fig. 5. There was no significant difference in sex ratio, age or baseline body weight according to the χ 2 test and Kruskal−Wallis test.

Relationships between Web recording, coffee consumption and self-weighing
There was a high correlation between P REC |P CONS and P REC |P WEIGH (0.829; 95% CI: 0.825, 0.832). Partial correlation coefficients were calculated to exclude the effect of pseudo-correlations. The partial correlation coefficients between P REC and P REC |P CONS with P REC |P WEIGH as a covariate, and between P REC and P REC |P WEIGH with P REC |P CONS as a covariate were 0.708 (95% CI: 0.700, 0.716) and 0.605 (95% CI: 0.596, 0.613), respectively.

Discussion
Consumption of chlorogenic acid-enriched coffee was associated with monotonic weight loss during the ad libitum and add-on consumption periods, i.e., −0.51 kg at Week 4, −0.84 kg at Week 8, and −1.06 kg at Week 12. Obese participants lost more weight than normal-weight participants (Fig. 4).
These results suggest that habitual consumption of chlorogenic acid-enriched coffee, together with the use of the weight-recording system, supported weight loss during daily life, especially in obese participants.
Out of the total of 25,441 participants, 16,928 (66.5%) completed the ad libitum consumption period, suggesting good acceptability of the coffee for everyday use, which is an important factor from a public health perspective. Japanese adults drink an average of around 11 cups of coffee a week [28], and substituting one cup of coffee a day with  [32]. Moreover, Japanese people tend to be diagnosed with type 2 diabetes without associated severe obesity [11].

Conclusions
The habitual consumption of chlorogenic acid-enriched coffee together with the use of a weight-  [29].
There were some demographic differences between the ad libitum and add-on consumption periods.
The percentage of women was smaller during the add-on period, resulting in a higher baseline weight and BMI. This suggests that the motivation for and dedication to weight loss might differ between men and women, possibly associated with the fact that men have a higher prevalence of metabolic syndrome [30].
One of the limitations of the present study was compliance monitoring, owing to the difficulty of confirming data for such a large number of participants.
However, imprecision in measurement of weight is not likely to be a serious issue [31] compared with most biochemical or physiological measurements.
Furthermore, digital bathroom-type scales are commonly used at home in Japan, thus the precision is much higher than with the use of spring-type scales, which were popular before 2000. A further limitation was the lack of a control group. However, adopting the single-arm study design approach enabled us to enroll a large number of participants from a wide population, because it was much easier to obtain their informed consent compared with a randomised controlled trial design approach.
The observed weight loss within 12 weeks could be considered to be relatively small (−1.06 kg).
However, a meta-analysis of 25 randomised control trials has estimated that a decrease of 1 kg in body Nutrafoods (2014) 13:103-111