以人體試食試驗評估柑橘幼果萃取物與8小時限時進食法在改善肥胖成年人體重與體脂肪之功效：一項隨機對照臨床試驗

當今飲食型態易導致國人攝取過多的精緻糖與油脂，再加上每日活動量不足的情況下，導致現代人的過重與肥胖盛行率逐年上升，乃不容忽視的健康問題之一。過重與肥胖可藉由服用膳食補充劑與採用間歇性斷食法進行改善。先前研究指出，柑橘幼果富含黃酮類與多酚類，其擁有的植化素含量與抗氧化能力更勝成熟柑橘。另外，8小時進食搭配16小時空腹的間歇性斷食法，亦稱為8小時限時進食法 (8-hour time-restricted eating, 168)，也有研究顯示能夠有效降低體重，並促進健康。本研究將以自身對照的方式，評估柑橘幼果萃取物 (immature ponkan extract, IPE) 對於過重與肥胖人群在改善體重與體脂肪的功效。本實驗將300位20-60歲身體質量指數 (body mass index, BMI) ≥ 24 kg/m2或體脂肪 > 30%的男女性隨機分配至三組 (n = 100)：(1) 柑橘幼果萃取物組 (IPE)、(2) 柑橘幼果萃取物搭配8小時限時進食法組 (IPE + 168) 及 (3) 安慰劑組 (placebo)，試驗為期八週，每日飲用一包25毫升之安慰劑或柑橘幼果萃取物。於服用前、服用後4和8週進行體位測量、飲食問卷、體感問卷及血液與糞便檢體採集，進一步分析其腸道菌相及短鏈脂肪酸含量。試驗結果顯示，與第0週相比，服用4週後，受試者的體重、身體質量指數與體脂肪率皆顯著降低；IPE + 168組別在8週後，其體重、身體質量指數、腰圍與臀圍皆顯著下降。體內氧化壓力的分析結果指出，IPE組的相對總抗氧化能力呈現顯著增加。糞便短鏈脂肪酸含量結果顯示，介入8週柑橘幼果萃取物後，糞便中乙酸、丙酸和總短鏈脂肪酸含量較介入前顯著增加。此外，腸道菌相結果表示，IPE + 168組在介入8週後，較介入前顯著增加Bacteroridete、 Bacteroidia、 Bacteroidales和Bacteroidaceae和Bacteroides之相對豐富度，亦明顯減少Firmicutes、 Lachnospiraceae、 Ruminococcaceae的相對豐富度。另外，服用柑橘幼果萃取物8週後亦可顯著降低Firmicutes/Bacteroridete之比值、Clostridia、 Betaproteobacteria、 Bacilli、 Clostridiale、 Burkholderiale、Lactobacillales、Blautia和Faecalibacterium之相對豐富度。體感問卷結果指出，試驗期間服用柑橘幼果萃取物可顯著改善體態問題 (大肚腩和體態鬆軟不結實) 與腸胃道症狀 (便祕和腹脹)，而搭配8小時限時進食法則可改善體態問題 (身體沉重感、大肚腩和體態鬆軟不結實)、調節食慾 (飲食過量和容易嘴饞)。總結上述結果可知，服用柑橘幼果萃取物與8小時限時進食法後，可有效改善肥胖相關指標、提升抗氧化力，以及具有調節腸道菌相之作用。

The contemporary dietary patterns are conducive to excessive consumption of refined sugars and fats. In conjunction with the lack of daily physical activity observed in modern society, leading to a rise in the prevalence of overweight and obesity, which represents a significant public health concern. The management of overweight and obesity can be achieved through the use of dietary supplements and intermittent fasting. Previous studies have pointed out that immature citrus fruits are rich in flavonoids and polyphenols, and their phytochemical content and antioxidant capacity are superior to those of mature citrus. Additionally, intermittent fasting with 8 hours of eating and 16 hours of fasting, also known as 8-hour time-restricted eating (168), has been shown to effectively reduce body weight and promote health. The objective of this study is to evaluate the efficacy of immature ponkan extract (IPE) in improving body weight and body fat in overweight and obese individuals using a self-controlled study. In this study, 300 participants aged 20-60 years with a body mass index (BMI) ≥ 24 kg/m2 or body fat > 30% were randomly assigned to three groups (n = 100): (1) immature ponkan extract (IPE) group, (2) immature ponkan extract with 8- hour time-restricted group (IPE + 168), and (3) placebo group (placebo). Participants were administered a 25 mL sachet of placebo or immature ponkan extract daily for 8 weeks. Anthropometric measurements, dietary questionnaires, health questionnaires, and blood and fecal samples were aquired at week 0, 4, and 8. Furthermore, the intestinal microbiota and short-chain fatty acid content will be analyzed after the 8-week trial. The results demonstrated a significant reduction in body weight, BMI, and body fat percentage following four weeks of IPE consumption compared to those of the week 0. Meanwhile, the body weight, BMI, waist circumference, and hip circumference were decreased significantly after 8 weeks of IPE + 168 treatment. The analysis of antioxidant capacity indicated that the relative TEAC was significantly increased in the IPE group. Analysis of fecal short-chain fatty acid (SCFA) content revealed a significant increase in acetic acid, propionic acid, and total SCFA content in the feces after 8 weeks of IPE intervention. Additionally, the results of the gut microbiota showed that the relative abundance of Bacteroridete, Bacteroidia, Bacteroidales, Bacteroidaceae, and Bacteroides were significantly increased as well as the relative abundance of Firmicutes, Lachnospiraceae, and Ruminococcaceae were decreased after 8 weeks of IPE group and IPE + 168 group compared to those of week 0. The 8-week IPE treatment significantly reduced the Firmicutes/Bacteroridete ratio, Clostridia, Betaproteobacteria, Bacilli, Clostridiale, Burkholderiale, Lactobacillales, Blautia, and Faecalibacterium. According to the results of the health questionnaire, the body-shape problems (pot-belly and flabby body) and gastrointestinal symptoms (constipation and flatulence) were significantly improved after IPE intervention. Additionally, IPE + 168 further significantly reversed the body-shape problems (heaviness, pot-belly, and flabby body) and regulated the appetite (overeating and discretionary snacking). In conclusion, immature ponkan extract and 8-hour time-restricted eating can markedly ameliorated obesity-related indicators and enhance antioxidant capacity, as well as reverse the gut microbiome dysbiosis.