Written by Tabish Mehraj, PhD, Science Writer. This study evaluated the tolerability and efficacy of a food supplement containing citrus lemon extracts in individuals with impaired fasting glycemia (IFG). The treatment group showed significant improvements in fasting-state glycemia after 3 months, with normalization of glucose levels (p<0.001 vs T0), unlike the placebo group. Improvements were also observed in the overall lipid profile. 

Impaired fasting glycemia (IFG) is a significant metabolic condition which is associated with an increased risk of developing certain cardiovascular diseases and type 2 diabetes. The main interventions to reverse and mitigate disease progression are lifestyle modifications, including diet and physical exercise. Food supplements offer a great way to manage metabolic risk factors with fewer side effects compared to conventional pharmacological treatments. This study investigates the efficacy and tolerability of a specific food supplement (FS) containing extracts from Citrus limon L. Osbeck and Vitis vinifera L., hesperidin from Citrus sinensis L. Osbeck, and chromium, in combination with an isocaloric diet, on lipid metabolism and glucose in individuals with IFG.

This study, conducted by Alessandro and team at the Department of Pharmacy, University of Napoli Federico II, Naples, Italy, used a single-center, controlled, randomized, parallel-arm, double-blind clinical trial. 62 subjects (aged 18–75 years) with IFG (fasting glucose levels between 100–125 mg/dL) were divided into two groups: a treatment group receiving the food supplement and a placebo group (n=31 per group). The enrolled participants took two tablets daily containing 250 μg of chromium and 560 mg of flavonoids: 480 mg hesperidin, 75 mg eriocitrin, and 5 mg of other flavonoids. The biochemical parameters related to lipid metabolism and glucose, as well as markers of kidney and liver functionality, were analyzed at baseline (T0), after 3 months (T1), and after 6 months (T2). A number of parameters were assessed following the treatment, the primary outcome being the clinical efficacy of the FS in reducing fasting plasma glucose levels, fasting insulin (INS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), body mass index (BMI), waist circumference (WC), blood pressure (DBP, SBP), and inflammatory markers (WBC, ESR, CRP). Safety was monitored through liver (AST, ALT) and kidney (CRE) function tests. Statistical analysis used a random-intercept linear mixed model (LMM).

The significant findings are as follows:

• Glucose Metabolism

The treatment group demonstrated a significant improvement in fasting glycemia after 3 months, with glucose levels normalizing to an average of 95 mg/dL (p < 0.001 vs. T0) and remaining stable at T2. HbA1c levels decreased significantly in the treatment group, with an overall reduction from T0 to T2 (p = 0.0036). The HOMA-IR index showed a significant decrease in the treatment group between T0 and T2 (p = 0.010), unlike in the placebo group, suggesting improved insulin sensitivity.

• Lipid Metabolism

The food supplement showed a positive impact on lipid profiles. Total cholesterol (TC) levels significantly decreased in the treatment group between T0 and T1 (p < 0.001), returning to the normal range (average 149 mg/dL) and remaining stable. LDL-C levels decreased significantly in the treatment group between T0 and T2 (p < 0.001), reaching an average of 73 mg/dL, which was significantly lower than in the placebo group at both T1 and T2. Triglyceride (TG) levels significantly decreased in the treatment group between T0 and T1 (p = 0.0096) and remained stable, resulting in a significant overall decrease from T0 to T2 (p = 0.011).

One of the primary strengths of this study is its randomized, double-blind, placebo-controlled design, which reduces bias and strengthens the internal validity of the findings. The use of a well-defined population (individuals with IFG) and a standardized dietary intervention (an isocaloric DASH diet) increases the reliability of results. Monitoring safety parameters, such as liver and kidney function, throughout the study is important for understanding the supplement’s safety profile.

Despite its strengths, the study has several limitations. The absence of a post-intervention follow-up limits conclusions about the long-term stability of the observed beneficial effects. It is unclear whether the improvements in glucose and lipid metabolism would be sustained after cessation of the supplement. Secondly, a relatively small sample size (n=31 per group) might limit the generalizability of the findings. Thirdly, the study was single-center, which may introduce specific population characteristics. Finally, the study focused on individuals with IFG and normal HbA1c levels, meaning the findings may not be directly applicable to individuals with more advanced stages of prediabetes or diagnosed T2DM.

This clinical trial provides promising evidence that a food supplement combining Citrus limon, Vitis vinifera extracts, hesperidin, and chromium, when paired with an isocaloric diet, significantly enhances lipid metabolism in subjects with impaired fasting blood glucose. The supplement led to normalization of fasting glucose, reduction in HbA1c and LDL-C, and increases in HDL-C, alongside improved insulin sensitivity. These findings suggest that this combination of bioactive ingredients offers a valuable strategy for managing early metabolic dysregulation and potentially delaying the progression to T2DM and cardiovascular complications. However, larger, multi-center studies with longer follow-up periods are warranted to confirm these results and further elucidate the long-term efficacy and broader applicability of this food supplement.

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Posted April 16, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi. 

References:

1. Di Minno, A., Morone, M. V., Buccato, D. G., De Lellis, L. F., Ullah, H., Borromeo, L., … & Daglia, M. (2025). Impact of a food supplement containing Citrus limon L. Osbeck and Vitis vinifera L. extracts, hesperidin and chromium in combination with an isocaloric diet on glucose and lipid metabolism in subjects with impaired fasting blood glucose: a single-center, controlled, randomized, parallel-arm, double-blind clinical trial. Frontiers in Nutrition, 12, 1671102.