Individuals with elevated serum cholesterol levels were included in this study, which was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (No. [2017]325–03) and registered at the China Clinical Trial Registration Center (Registration No. ChiCTR1800015904). All participants were informed of the purpose, content, and risks involved with study participation; written informed consent was collected prior to the commencement of the trial.

Inclusion criteria: (1) Cholesterol: Total Cholesterol (TC) ≥ 5.2 and < 7.2 mmol/L, and/or Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 3.4 and < 4.9 mmol/L; (2) Age: 35–65 years; (3) Cholesterol elevation without prior or recent lipid-lowering treatment.

Exclusion criteria: (1) Platelet count <100 × 10^9/L; (2) Coagulation disorders; (3) Recent use of aspirin or other platelet/coagulation modifiers; (4) Consumption of fish oil or evening primrose oil supplements within the last month; (5) Regular consumption of tomatoes and their products (≥ 5 days/week); (6) Tomato allergy; (7) Pregnancy or lactation; (8) Major cardiovascular, hepatic, renal, or endocrine disorders; (9) Non-consent.

The study was conducted as a prospective, randomized, double-blind, placebo-controlled clinical trial design. Sixty participants were sequentially allocated random codes by an independent third party. The study lasted for 60 days, including a 45-day intervention period followed by a 15-day follow-up. Throughout the intervention phase, participants were administered the trial product, which was either WSTC or a placebo, orally with meals at a dose of 300 mg twice daily. Administration was discontinued during the follow-up period. Each 300 mg tablet of WSTC contained 150 mg of Fruitflow, including flavonoids, adenosine, and chlorogenic acid, sourced from DSM (China) Co., Ltd. The remaining half of the tablet weight was made up of excipients, such as microcrystalline cellulose, lactose, and magnesium stearate, and was coated with a sugar film. The placebo consists of the same excipients as Fruitflow (including microcrystalline cellulose, lactose, and magnesium stearate), formulated into 300 mg tablets and sugar-coated. Its shape, size, color, and taste are indistinguishable from Fruitflow tablets.

Assessment and Measurement of Relevant Indices at Pre-Intervention (Day 0), Post-Intervention (Day 45), and End of Follow-Up (Day 60).

Physical activity is quantified using the Chinese version of the International Physical Activity Questionnaire (iPAQ) Short Form (16), with weekly activity levels expressed in MET-minutes/week. Dietary intake of vegetables and fruits is assessed through the Food Frequency Questionnaire (FFQ), and daily energy intake is calculated according to the China Food Composition (2nd Edition).

Randomization is conducted by non-research personnel, with study implementation and data collection handled by the research team. Blinding is lifted post-study, and analysis is performed solely on data from participants who completed the study. Normal distribution data are presented as mean ± standard deviation (xˉ ± s), while non-normal data are expressed as median (interquartile range) M (P25, P75). Group comparisons for parametric data use independent sample t-tests, and paired t-tests for within-group temporal comparisons. Non-parametric data employ rank-sum tests. Analyses are conducted using SPSS 23.0, with two-sided tests and a significance threshold set at p < 0.05.

The study enrolled 60 participants, evenly divided with 30 in the Fruitflow Group (FFG) and 30 in the Placebo Control Group (PCG). All 60 subjects completed the intervention, with 59 completing the follow-up (as illustrated in Figure 1). Detailed demographic and baseline characteristics, presented in Table 1, show no significant differences between the FFG and PCG across measured indicators (p > 0.05).

In the FFG, a 4.2% reduction in systolic blood pressure (SBP) was observed after 45 days of intervention (p < 0.001), which was significantly lower than in the PCG (p = 0.041). The follow-up period showed a 1.5% increase in SBP (p = 0.032), yet it remained below the baseline level. Diastolic blood pressure (DBP) decreased by 3.8% (p = 0.015). In contrast, no significant changes in SBP and DBP were observed in PCG during the intervention and follow-up. Detailed data can be found in Table 2.

Further stratified analysis based on hypertension status revealed significant reductions in SBP in FFG after the 45-day intervention (p < 0.05), regardless of hypertension status, with a minor decrease in DBP (p > 0.05). In non-hypertensive FFG subjects, SBP was significantly lower than that in controls. In PCG, no significant changes in SBP or DBP were observed during the intervention and follow-up. Detailed findings are presented in Table 2.

After a 45-day intervention, the FFG showed a significant increase in HDL-C by 6.5% (p = 0.018). However, levels of TG, TC, and LDL-C did not change significantly. In the PCG, there were no significant changes observed in these lipid parameters. Additionally, no significant differences were observed between the groups. Detailed information is provided in Table 3.

As shown in Table 3, baseline levels of hs-CRP showed no statistical difference between the FFG and the PCG (p = 0.271). FFG exhibited a decreasing trend in hs-CRP levels, in contrast to an increasing trend in PCG. At the end of the follow-up, hs-CRP levels in FFG were significantly lower than those of PCG (p = 0.022). Both groups experienced significant reductions in Hcy levels during the intervention (FFG: -5.4%, p = 0.028; PCG: -13.4%, p = 0.006), with FFG continuing to decrease (−8.5%, p < 0.001) and PCG showing an increase (+4.8%, p < 0.001) at follow-up, resulting in significantly lower Hcy levels in FFG compared to PCG (p = 0.008). For FBG, no significant difference was observed between FFG and PCG at baseline (p = 0.169). Post-intervention, FBG levels decreased in FFG, while remaining stable in PCG. By the end of the follow-up, FBG levels in FFG were significantly lower than those of PCG (p = 0.029).

Post-intervention and during the follow-up, both body weight and BMI showed significant reductions in the FFG and displayed statistical differences compared to the PCG (p < 0.05). The PCG exhibited no significant changes in weight and BMI throughout the intervention and follow-up periods (p > 0.05). Changes in body fat percentage (BF%) were not significant in either group. Details are provided in Table 4.

Neither the FFG nor the PCG showed significant changes in physical activity levels during the intervention and follow-up periods (p > 0.05). Total energy, vegetable, and fruit intakes remained consistent across both groups throughout these periods (p > 0.05).

Before and after the intervention, coagulation, liver, and kidney function parameters remained within normal ranges for participants in both groups.

Our results indicate that Fruitflow effectively decreases blood pressure levels in individuals with hypercholesterolemia, particularly SBP, demonstrating partially sustained efficacy. This significant impact on blood pressure regulation is one of the key highlights of our research. During the intervention period with Fruitflow, notable reductions in both SBP and DBP were observed, with these lower levels being maintained for 15 days post-intervention. Notably, the effect of Fruitflow on reducing blood pressure was observed regardless of the presence of hypertension. Existing research supports our hypothesis that the antihypertensive action of Fruitflow is intrinsically linked to its rich composition of flavonoids, adenosine, and chlorogenic acid.

Based on this, studies have shown that flavonoid-rich plant extracts act as natural inhibitors of Angiotensin-Converting Enzyme (ACE), thereby functioning as natural ACE inhibitors (ACEIs) (17). Specifically, chlorogenic acid, classified as a phenolic acid within the polyphenol category, has been demonstrated to inhibit and downregulate ACE and renin expression (18). This effect contributes to the synthesis of endothelial Nitric Oxide (NO) (19), inducing vasodilation and consequent blood pressure reduction. Furthermore, adenosine, known for its role in immune and inflammatory pathways, can mitigate various inflammatory disorders, thus modulating vascular inflammatory damage (20). Complementing these findings, research by Biswas et al. (21) has revealed that WSTC inhibits ACE activity in rat lungs. Based on these insights, we propose that Fruitflow may exert its antihypertensive effects through anti-inflammatory mechanisms, by enhancing endothelial function, increasing NO release, and reducing ACE and renin levels. Therefore, this study provides substantial clinical evidence supporting Fruitflow’s role in blood pressure management, particularly for hypercholesterolemic populations. However, the precise underlying mechanisms of these effects warrant further detailed investigation.

Apart from its anti-hypertensive properties, our study reveals multiple beneficial effects of Fruitflow in individuals with elevated cholesterol. These effects include: (i) A significant increase in HDL-C levels indicates that Fruitflow is beneficial for reducing the risks of cardiovascular diseases. Since HDL-C is inversely correlated with the risk of coronary heart disease, its beneficial roles extend beyond reverse cholesterol transports (22, 23). These include anti-inflammatory and antioxidant properties, thrombosis inhibition, and the enhancement of endothelial function, collectively mitigating arteriosclerosi. (ii) Reduction in FBG levels. Elevated FBG is a key contributor to arteriosclerosis, primarily due to mechanisms such as advanced glycation end-product formation, insulin resistance, and polyol metabolism abnormalities, leading to endothelial dysfunction, oxidative stress, and the release of pro-inflammatory cytokines, thus accelerating arteriosclerosis (24). (iii) Decrease in hs-CRP levels. As a significant predictor of cardiovascular diseases, high hs-CRP levels are involved in both localized and systemic inflammatory responses, impairing endothelial cells, reducing NO and prostaglandin release, upregulating Angiotensin I receptors, and affecting renin and angiotensin levels, which contribute to endothelial cell proliferation, intimal thickening, and arteriosclerosis progression (25, 26). (iv) Notable reduction in Hcy levels, with this effect persisting for 15 days post-intervention. Hyperhomocysteinemia (HHcy) is associated with oxidative stress, endothelial dysfunction, arterial stiffening, and angiotensin activation (27). Epidemiological studies in Chinese populations have demonstrated HHcy’s significant role in increasing hypertension risk (28, 29) and as an independent risk factor for the one-year recurrence of acute ischemic stroke (30). (v) Substantial reduction in both body weight and BMI. Therefore, Fruitflow exhibits a protective role against arteriosclerotic cardiovascular diseases, achieved by elevating ‘good cholesterol’ levels and reducing FBG, hs-CRP, Hcy, body weight, and BMI, thus proving beneficial for cardiovascular health.

After the intervention with Fruitflow, there were no abnormalities in the coagulation function, liver function, and kidney function of the subjects, and no adverse events occurred during the trial period, indicating that Fruitflow is safe.

In summary, this study indicates that Fruitflow effectively lowers blood pressure in individuals with hypercholesterolemia and positively modulates cardiovascular risk factors, with sustained effects. The limited sample size and brief duration of the intervention in this study may lead to certain underestimations. Specifically, the small sample size could underestimate diet’s impact on the study outcomes. Future studies would benefit from a larger sample size to enable stratified randomization of potential confounding factors. Moreover, the short duration of the trial might result in underestimate the long-term effects of Fruitflow on cardiovascular health, highlighting the need for a longer intervention period. Overall, these improvements will provide a robust scientific basis for using Fruitflow in the precise management of hypertension and contribute to developing novel approaches for utilizing bioactive food components in the prevention and management of cardiovascular diseases.