Nutraceuticals Against the Silent Killers: Role of Secondary Metabolites in the Prevention and Management of Hypertension and Hyperlipidemia

Muhammad Qamar¹ , Eisha Ismail², Muhammad Zulqarnain Khan¹, Bushra Irum Fatim¹,
Maryam Jalal Ud Din¹ and Malik Waseem Abbas³
1. Department of Food Science and Technology, Faculty of Food Science and Nutrition, Bahauddin Zakariya University, Multan, Pakistan
2. Multan Medical and Dental College, Multan, Pakistan
3. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan
Correspondence to: Muhammad Qamar, muhammadqamar@bzu.eu.pk; muhammad.qamar44@gmail.com

DOI: https://doi.org/10.70389/PJC.100013

Additional information

• Ethical approval: N/a
• Consent: N/a
• Funding: No industry funding
• Conflicts of interest: N/a
• Author contribution: Muhammad Qamar: Conceptualization; Muhammad Qamar, Muhammad Zulqarnain Khan, Eisha Ismail, Bushra Irum Fatim, Maryam Jalal Ud Din and Malik Waseem Abbas: Investigation and resources; Muhammad Qamar, Muhammad Zulqarnain Khan: Writing — original draft preparation; Muhammad Qamar: Project administration. All authors have read and agreed to the published version of the manuscript
• Guarantor: Muhammad Qamar
• Provenance and peer-review:
  Unsolicited and externally peer-reviewed
• Data availability statement: N/a

Keywords: Quercetin, Epigallocatechin-3-gallate, Anthocyanins, ace inhibition, cetp inhibitions.

Peer Review
Received: 16 August 2025
Last revised: 10 September 2025
Accepted: 10 September 2025
Version accepted: 3
Published: 23 September 2025

Plain Language Summary Infographic

List of Abbreviations:

• CVD: Cardiovascular diseases
• EGCG: Epigallocatechin-3-gallate
• LDL-C: Low-density lipoprotein cholesterol
• HDL-C: High-density lipoprotein cholesterol
• ACE: Angiotensin-converting enzyme
• CETP: Cholesteryl ester transfer protein
• HTN: Hypertension
• SBP: Systolic blood pressure
• DBP: Diastolic blood pressure
• TC: Total cholesterol
• SCAP–SREBP2–LDLr: SCAP (SREBP cleavage-activating protein)-SREBP2 (sterol regulatory element-binding protein 2)-LDLr (low-density lipoprotein receptor)
• TNF-α: Tumor necrosis factor alpha
• CRP: C-reactive protein
• TAG: Triacylglycerols
• VCAM-1: Vascular cell adhesion molecule 1

Introduction

Cardiovascular diseases (CVDs) account for nearly 31% of global mortality,¹ with hypertension and hyperlipidemia serving as major modifiable risk factors.^2,3 These “silent killers” often remain asymptomatic until advanced stages, contributing to atherosclerosis, stroke, and myocardial infarction.⁴ Dyslipidemia, marked by elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides, affects over 100 million Americans alone,⁵ while hypertension impacts 1.3 billion globally, with rising prevalence in aging populations.⁶ Both conditions synergistically accelerate vascular damage,⁷ yet underdiagnosis persists, particularly in younger adults.⁵ Conventional therapies, i.e., use of aspirin, beta-blockers, statins, and angiotensin-converting enzyme inhibitors, though effective, face limitations like adverse effects and poor adherence,^8–10 driving interest in nutraceuticals as preventive and adjunctive therapy.¹¹

Bioactive secondary metabolites are found to demonstrate cardioprotective potential by improving lipid metabolism, endothelial function, and oxidative stress.^12,13 For instance, quercetin, epigallocatechin-3-gallate (EGCG), and anthocyanins are reported to reduce LDL-C and blood pressure (BP) in a range of clinical trials.^14–16 Functional foods enriched with these compounds may offer scalable, cost-effective solutions, aligning with lifestyle interventions. This review explores the role of plant-derived nutraceuticals in the management of hypertension and hyperlipidemia, emphasizing mechanistic insights, clinical evidence, and future translational potential to curb CVD progression.

Methodology and Quality of Evidence

The articles were retrieved from the electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar. The investigation employed specific search strings with Boolean operators: “quercetin” AND (“blood pressure” OR “hypertension” OR “lipid profile”); (“epigallocatechin gallate” OR “EGCG”) AND (“cholesterol” OR “hyperlipidemia” OR “blood pressure”); and “anthocyanins” AND (“hypertension” OR “dyslipidemia” OR “clinical trial”). The search was limited to publications from the year 2000 through April 2024.

The criteria for inclusion in the narrative review were: peer-reviewed clinical trials or randomized controlled trials (RCTs) that specifically investigated antihypertensive or lipid-lowering effects in mmHg or lipid concentrations (mmol/L or mg/dL). Excluded works were non-English publications, studies conducted solely on animals or in vitro, case reports, and conference abstracts for which a full text was unavailable. The selection process involved a sequential screening of titles and abstracts, followed by a thorough examination of the full-text articles. Studies were excluded at the full-text stage if they lacked a control group or failed to provide measurable cardiovascular outcomes. The strength of evidence varied across compounds, wherein overall certainty for quercetin in hypertension and hyperlipidemia is moderate, for EGCG is moderate-to-high, and for anthocyanins is low-to-moderate.

Evidence-Based Antihypertensive and Antihyperlipidemic Effects of Nutraceuticals

The BP- and LDL-C-lowering impact of quercetin, EGCG, and anthocyanins can be seen in Tables 1 and 2, respectively. The values presented below are compared to baseline, i.e., within-group.

Table 1: Nutraceuticals and their antihypertensive potential.
Citation	Subjects	Dose and Duration	Results
Quercetin
Egert et al.15	150 mg/day for 6 weeks vs baseline	93 overweight or obese individuals	↓ SBP: 2.9 mmHg in hypertensive subjects; p < 0.01 ↓ SBP: 3.7 mmHg in younger adults; p < 0.01
Lee et al.17	100 mg/day for 10 weeks vs baseline	n = 49	↓ SBP: 3 mmHg; p < 0.01 ↓ DBP: 3 mmHg; p < 0.01
Zahedi et al.22	500 mg/day for 10 weeks vs baseline	72 women with type 2 diabetes	↓ SBP: 8.8 mmHg; p < 0.04 ↓ DBP: 1–2 mmHg; p < 0.19
Edwards et al.21	730 mg/day for 4 weeks vs baseline	19 men and women with prehypertension 22 stage 1 hypertension	↓ SBP: 7 mmHg; p < 0.01 ↓ DBP: by 5 mmHg; p < 0.01 ↓Arterial pressure by 5 mmHg; p < 0.01
Larson et al.19	1095 mg/day for 1 week vs baseline	12 stage 1 hypertensive 5 normotensive men	↓ SBP: 7 mmHg; p < 0.01 ↓ DBP by 3 mmHg; ns
EGCG
Bogdanski et al.32	208 mg/day for 3 months vs baseline	56 obese, hypertensive patients	↓ SBP: −4 mmHg; ns↓ DBP: −4 mmHg; ns
Brown et al.38	400 mg twice daily (800 mg/day) for 8 weeks vs baseline	40 overweight/obese men (age 40–65)	↓ SBP: −2.85 mmHg; p = 0.096↓ DBP: −2.68 mmHg; p = 0.014
Chatree et al.34	300 mg/day for 8 weeks vs baseline	30 obese adults	↓ SBP: −7 mmHg; p < 0.05↓ DBP: −4 mmHg; p < 0.05
Hsu et al.37	302 mg/day for 12 weeks vs baseline	78 obese women	↓ SBP: −3.6 mmHg; ns↓ DBP: −1.2 mmHg; ns
Chen et al.35	856.8 mg/day for 12 weeks vs baseline	115 women with central obesity	↓ SBP: −2 mmHg; ns↓ DBP: −1 mmHg; ns
Anthocyanins
Broncel et al.42	300 mg/day for 2 months vs baseline	25 patients with metabolic syndrome	↓ SBP: −12.2 mmHg; p < 0.001↓ DBP: −5 mmHg; p < 0.05
Igwe et al.48	369 mg/day for 2 weeks vs baseline	12 older adults (65+ years) and 12 younger adults (18–45 years)	↓ SBP in older adults: −12.83 mmHg; p = 0.001
Cook et al.47	300 mg/day for 6 days vs baseline	14 older adults (69 ± 4 years)	↓ SBP: −6 mmHg; p < 0.05↓ DBP: −6 mmHg; p < 0.05
Okamoto et al.16	300 mg/day for 7 days vs baseline	14 older adults (73.3 ± 1.7 years)	↓ SBP: −9 mmHg; p = 0.001↓ DBP: −3 mmHg; ns
Johnson et al.46	469 mg/day for 8 weeks vs baseline	48 postmenopausal women with pre-/stage 1 hypertension	↓ SBP: −7 mmHg; p < 0.05↓ DBP: −5 mmHg; p < 0.01
Basu et al.45	742 mg/day for 8 weeks vs baseline	48 obese adults with metabolic syndrome	↓ SBP: −7.8 mmHg (prehypertensive); p < 0.05↓ DBP: −2.5 mmHg (prehypertensive); ns
SBP = Systolic blood pressure; DBP = Diastolic blood pressure.

Table 2: Nutraceuticals and their antihyperlipidemia potential.
Citation	Population	Dosage and Duration	Total Cholesterol	Triacylglycerol	LDL-C	HDL-C	Adverse Effects
EGCG
Mielgo-Ayuso et al.39	Obese women (n = 83)	300 mg/day (12 weeks) vs baseline	↓ (4.81 → 4.42 mmol/L) p < 0.05	↓ (2.52 → 2.21 mmol/L) p > 0.2	↓ (2.78 → 2.68 mmol/L) p < 0.05	↓ (1.42 → 1.29 mmol/L) p < 0.05	No adverse effects
Wu et al.40	Postmenopausal women (n = 103)	400 mg/day (2 months) vs baseline	↓ (218 → 207 mg/dL) p = 0.012	↓ (107 → 106 mg/dL) p = 0.012	↓ (129 → 119 mg/dL) p = 0.007	No change
Samavat et al.13	Postmenopausal women (n = 936)	843 mg/day (6–12 months) vs baseline	↓ (206 → 199.4 mg/dL) p < 0.001	↑ (93 → 94.6 mg/dL) ns	↓ (118 → 112.3 mg/dL) p = 0.0001	↓ (70 → 68.7 mg/dL) ns	Not reported
Chen et al. (2015)	Obese women (n = 115)	856.8 mg/day (12 weeks) vs baseline	↓ (198.8 → 183.9 mg/dL) p = 0.005	↑ (129.9 → 132.0 mg/dL) ns	↓ (124.7 → 112.1 mg/dL) p = 0.006	↓ (49.2 → 47.0 mg/dL) ns	No adverse events reported
Hsu et al.37	Obese women (n = 336)	400 mg/day (12 weeks) vs baseline	↓ (211.3 → 202.7 mg/dL) ns	↓ (141.4 → 135.7 mg/dL) p = 0.01	↓ (150.6 → 134.5 mg/dL) p < 0.001	↑ (42.5 → 44.1 mg/dL) p < 0.05	3 had mild constipation and 2 had abdominal discomfort
Lu and Hsu38	Women with acne (n = 80)	856 mg/day (4 weeks) vs baseline	↓ (174.5 → 163.8 mg/dL) p < 0.05	↓ (88.7 → 80.2 mg/dL) ns	↓ (93.9 → 90.3 mg/dL) ns	No change	1 had mild constipation and 3 had abdominal discomfort
De Morais Junior et al.14	Healthy women (n = 14)	800 mg (acute, postprandial) vs baseline	↓ (151 → 139.9 mg/dL at 120 min) ns	↑ (89.9 → 126.0 mg/dL) p < 0.05	↓ (73 → 61.1 mg/dL) ns	↓ (60 → 53.5 mg/dL) ns	No adverse effects reported
Kajimoto et al.41	Hypercholesterolemic patients (n = 63)	197.4 mg ×2/day (12 weeks) vs baseline	↓ (228 → 220 mg/dL) p < 0.01	↓ (133.3 → 125.0 mg/dL) ns	↓ (145.9 → 137.0 mg/dL) p < 0.01	↑ (55.3 → 58.2 mg/dL) ns	No adverse effects reported
Quercetin
Egert et al.24	Overweight ApoE3 (n = 93)	150 mg/day (6 weeks) vs baseline	↓ (5.66 → 5.53 mmol/L) ns	↑ (1.70 → 1.68 mmol/L) ns	↓ (3.56 → 3.40 mmol/L) p < 0.05	↓ (1.35 → 1.28 mmol/L) p < 0.01	No adverse effects
Lee et al.17	Male smokers (n = 92)	100 mg/day (10 weeks) vs baseline	↓ (193.5 → 185.2 mg/dL) p < 0.05	↓ (163.5 → 156.9 mg/dL) ns	↓ (113.2 → 106.5 mg/dL) p < 0.01	↑ (44.3 → 51.4 mg/dL) p < 0.001	No adverse effects
Burak et al.23	Healthy (n = 67)	190 mg/day + ALA (8 weeks) vs baseline	↓ (4.68 → 4.35 mmol/L)	↓ (1.24 → 1.02 mmol/L)	↓ (2.62 → 2.39 mmol/L)	↑ (1.59 → 1.60 mmol/L)	No adverse effects
Nishimura et al.29	Elderly (n = 50)	60 mg/day (12 weeks) vs baseline	↑ (219.6 → 222.7 mg/dL) ns	↑ (110.7 → 119.3 mg/dL) ns	No change	↓ (68.8 → 67.4 mg/dL) ns	No adverse effects
Brüll et al.25	Overweight (n = 70)	162 mg/day (6 weeks) vs baseline	↓ (5.44 → 5.38 mmol/L) ns	↑ (1.81 → 1.83 mmol/L) ns	↓ (3.45 → 3.41 mmol/L) ns	↓ (1.39 → 1.36 mmol/L) ns	No adverse effects
Egert et al.15	Overweight/obese (n = 93)	150 mg/day (6 weeks) vs baseline	↓ (5.72 → 5.63 mmol/L) ns	↑ (1.82 → 1.94 mmol/L) ns	↓ (3.59 → 3.46 mmol/L) p < 0.05	↓ (1.35 → 1.28 mmol/L) p < 0.001	No adverse effects
Conquer et al.26	Healthy (n = 27)	1000 mg/day (4 weeks) vs baseline	↓ (5.08 → 4.90 mmol/L) ns	↓ (1.27 → 1.15 mmol/L) ns	↓ (2.84 → 2.82 mmol/L) ns	↑ (1.50 → 1.57 mmol/L) ns	Not reported
Zahedi et al.22	T2DM women (n = 72)	500 mg/day (10 weeks) vs baseline	↓ (189.2 → 188.6 mg/dL) ns	↓ (198.4 → 186.1 mg/dL) ns	↓ (106.1 → 105.9 mg/dL) ns	↓ (45.2 → 41.8 mg/dL) ns	No adverse effects
Nishihira et al.28	Elderly (n = 70)	50 mg/day (24 weeks) vs baseline	↑ (233 → 235 mg/dL) p < 0.05	↑ (106 → 112 mg/dL) ns	↑ (139 → 140 mg/dL) ns	↓ (76 → 75 mg/dL) ns	No adverse effects
Chopra et al.27	Healthy (n = 21)	30 mg/day (2 weeks) vs baseline	↑ (5.56 → 5.70 mmol/L) ns	↓ (1.19 → 1.18 mmol/L) ns	↑ (3.66 → 3.88 mmol/L) ns	↓ (1.36 → 1.29 mmol/L) ns	No adverse effects
Anthocyanins
Qin et al.49	Dyslipidemic (n = 120)	320 mg/day (12 weeks) vs baseline	↓ (226.2 → 220.5 mg/dL) ns	↓ (197.9 → 189.5 mg/dL) ns	↓ (159.2 → 139.9 mg/dL) p = 0.001	↑ (45.9 → 51.2 mg/dL) p = 0.001	No adverse effects
Zhu et al.51	Hypercholesterolemic (n = 122)	320 mg/day (24 weeks) vs baseline	–	–	–	↑ (5.26 → 5.40 mmol/L) ns	No adverse effects
Okamoto et al.16	Older adults (n = 14)	210 mg/day (7 days) vs baseline	–	↓ (88 → 85 mg/dL) ns	↓ (124 → 120 mg/dL) ns	↑ (73 → 76 mg/dL) ns	Not reported
Zhu et al.44	Hypercholesterolemic (n = 150)	320 mg/day (24 weeks) vs baseline	↓ (6.45 → 6.18 mmol/L) ns	↓ (2.45 → 2.35 mmol/L) ns	↓ (3.36 → 3.01 mmol/L) p = 0.036	↑ (1.22 → 1.37 mmol/L) p = 0.030	No adverse effects
Xu et al.52	Dyslipidemic (n = 176)	320 mg/day (6 weeks) vs baseline	↓ (6.33 → 6.21 mmol/L) p < 0.05	↑ (2.02 → 2.13 mmol/L) ns	↓ (4.33 → 4.16 mmol/L) p < 0.05	↑ (1.47 → 1.55 mmol/L) ns	No adverse effects
Li et al.50	T2DM (n = 58)	320 mg/day (24 weeks) vs baseline	↓ (5.07 → 4.88 mmol/L) p < 0.01	↓ (2.04 → 1.57 mmol/L) p < 0.01	↓ (3.17 → 2.92 mmol/L) p < 0.05	↑ (1.03 → 1.23 mmol/L) p < 0.01	No adverse effects
Lee et al.54	Obese (n = 63)	31.45 mg/day (8 weeks) vs baseline	↓ (227.6 → 178.6 mg/dL) p < 0001	↓ (182.4 → 130.5 mg/dL) p = 012	↓ (122.5 → 98.5 mg/dL) p < 0001	↓ (56.0 → 49.8 mg/dL) p < 0001	No adverse effects
Aboufarrag et al.53	Hyperlipidemic (n = 52)	320 mg/day (28 days) vs baseline	No change	No change	No change	No change	No adverse effects
EGCG = Epigallocatechin-3-gallate; LDL-C = Low-density lipoprotein cholesterol; HDL-C = High-density lipoprotein cholesterol; ns = Nonsignificant.

Quercetin

Quercetin, a dietary flavonol abundant in onions, apples, and leafy vegetables, has been extensively studied for its vascular health benefits.^15,17 The mechanism involved (Figure 1) is potentially able to augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.¹⁸ Additionally, quercetin inhibits angiotensin-converting enzyme (ACE), thereby reducing angiotensin II-mediated vasoconstriction, and mitigates oxidative stress by scavenging reactive oxygen species in vascular tissue.^19,20

Across RCTs, quercetin supplementation has demonstrated dose-dependent BP reductions, particularly in individuals with established hypertension.^{15,17,19,21,22} Egert et al.¹⁵ reported that 150 mg/day for 6 weeks reduced systolic BP (SBP) by 2.9 mmHg in hypertensive participants and 3.7 mmHg in younger adults, with no adverse effects. Similarly, Lee et al.¹⁷ found that 100 mg/day for 10 weeks reduced both SBP and DBP by 3 mmHg. At higher doses, Zahedi et al.²² observed a marked SBP reduction of 8.8 mmHg after 10 weeks of 500 mg/day in women with type 2 diabetes. Edwards et al.²¹ also showed that 730 mg/day for 4 weeks lowered SBP by 7 mmHg, DBP by 5 mmHg, and mean arterial pressure by 5 mmHg in stage 1 hypertensive patients, with no effect in prehypertensive individuals. Importantly, a high dose for short a duration (1095 mg/day for 1 week) caused a substantial reduction in SBP by 7 mmHg and DBP by 3 mmHg in stage 1 hypertensive men.¹⁹ Clinical evidence consistently shows that quercetin is most effective in individuals with stage 1 hypertension, with SBP reductions ranging from 2.9 to 8.8 mmHg depending on dose and duration.^15,21,22 Effects are modest in prehypertensive subjects, suggesting baseline BP influences responsiveness.²¹ Across studies, quercetin was well tolerated, with no significant adverse effects, reinforcing its potential as a safe adjunct to conventional antihypertensive therapy.

Overall, clinical evidence on quercetin’s effects on lipid profiles shows mixed but generally modest benefits, with outcomes influenced by dose, duration, population, and source. Moderate doses of 100–200 mg/day for 6–10 weeks in at-risk groups such as overweight individuals or smokers consistently reduced total cholesterol, LDL-C, and triglycerides, with occasional high-density lipoprotein cholesterol (HDL-C) increases.^23,24 Some of the clinical trials showed that quercetin intake influenced the lipid profile positively but in a nonsignificant manner.^25,26 Additionally, very low doses (<60 mg/day) often produced negative but negligible changes, especially in elderly or diabetic populations.^27–29 Combining quercetin with alpha-linolenic acid–enhanced triglyceride-lowering effects.²³ For lipid modulation, the most promising approach appears to be purified quercetin at 100–200 mg/day for at least 8 weeks in individuals with elevated cardiovascular risk, ideally alongside dietary and lifestyle interventions, while monitoring HDL-C responses. Quercetin exhibits antihyperlipidemic effects by modulating the SCAP–SREBP2–LDLr pathway, upregulating LDL-C receptor expression to enhance cholesterol clearance.³⁰ Additionally, it modulates gut microbiota composition, boosting short-chain fatty acid synthesis and inhibiting intestinal cholesterol absorption.31 Together, these mechanisms improve serum lipid levels and restore lipid homeostasis (Figure 1).

EGCG

The reviewed studies collectively demonstrate that EGCG, the primary bioactive polyphenol in green tea, exerts modest but consistent BP-lowering effects in individuals with obesity, hypertension, or metabolic syndrome. The mechanisms underlying EGCG’s antihypertensive effects are multifaceted. Primarily, EGCG enhances endothelial function by upregulating nitric oxide (NO) synthase activity, thereby promoting vasodilation.³² Additionally, it suppresses endothelin-1, a potent vasoconstrictor,³³ reduces oxidative stress via its antioxidant properties, and lowers mean arterial pressure.34 Studies also report reductions in proinflammatory biomarkers (e.g., TNF-α, CRP) and improvements in lipid metabolism, which may indirectly contribute to BP regulation.^34,35 The observed reductions in SBP (ranging from −2.85 to −7 mmHg) and DBP (−1.2 to −4 mmHg) across multiple RCTs suggest that EGCG supplementation may serve as a supportive intervention for improving cardiovascular health.32,34,36 Notably, these effects were evident at varying doses (208–856.8 mg/day) and durations (8–12 weeks), with no clear dose-dependent trend, implying that even lower doses (~200–300 mg/day) may suffice for BP modulation.^35,37 EGCG supplementation represents a potential adjunct therapy for mild BP reduction, particularly in metabolically compromised individuals.^32,34

EGCG demonstrates modest but consistent benefits in improving lipid profiles, particularly in reducing total cholesterol and LDL-C. Several RCTs support this effect, with reductions in LDL-C ranging from 3 to 10%.^13,38–40 The mechanisms behind these improvements likely involve the inhibition of cholesterol absorption, Upregulation of LDL-C receptors, and antioxidant effects. However, the effects on HDL-C and triacylglycerols (TAG) are less consistent. Some studies report HDL-C reductions,³⁹ while others show increases or no change.^37,38,41 These discrepancies may stem from differences in baseline metabolic health, dosage, or study duration. Notably, acute high-fat meal studies¹⁴ found that EGCG worsened postprandial TAG, possibly by delaying lipid clearance, i.e., a concern for individuals with metabolic syndrome.

Anthocyanins: Antihypertensive and Antihyperlipidemic Effects

Anthocyanins, a class of bioactive flavonoids found in deeply pigmented fruits including Aronia melanocarpa (chokeberry), blueberries, blackcurrants, and plums, have demonstrated significant BP-lowering effects in clinical studies. The BP-lowering effects are mediated through multiple pathways. Anthocyanins improve endothelial function by enhancing nitric oxide production, decreasing arterial stiffness by inhibiting vascular cell adhesion molecule 1 (VCAM-1), and reducing endothelin-1 levels.^16,42–44 Their antiinflammatory properties are demonstrated by reductions in proinflammatory cytokines, i.e., C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α),⁴⁵ while their antioxidant activity protects vascular tissues.⁴⁶

A range of clinical trials outlined that anthocyanin intake at doses of 300–742 mg/day for periods ranging from 6 days to 8 weeks shows consistent benefits, particularly in high-risk populations. In metabolic syndrome patients, studies by Broncel et al.⁴² and Basu et al.45 found reductions of 7.8–12.2 mmHg in SBP and 2.5–5 mmHg in DBP with anthocyanin supplementation. Older adults and postmenopausal women appear particularly responsive to anthocyanins. Johnson et al.46 reported 7 mmHg systolic and 5 mmHg diastolic reductions in postmenopausal women after 8 weeks of blueberry anthocyanin supplementation. Notably, even short-term interventions of 6–7 days with blackcurrant anthocyanins produced significant reductions of 6–9 mmHg systolic and 3–6 mmHg diastolic pressure in elderly participants.^16,47 Age-related differences in response were evident, with older adults showing greater BP reductions than younger individuals receiving the same plum juice anthocyanin dose.⁴⁸

Current evidence, while promising, has limitations including short durations (typically ≤8 weeks), small sample sizes (often <50 participants), and variability in anthocyanin sources and doses.^46–48 Future research should address these limitations through longer-term, larger-scale studies with standardized protocols to better establish anthocyanins’ role in BP management. The existing data suggest anthocyanin-rich foods or supplements may be particularly beneficial for hypertensive and older populations, offering a natural approach to cardiovascular risk reduction.

Anthocyanins demonstrate moderate but meaningful improvements in lipid metabolism, particularly in reducing LDL-C and increasing HDL-C. Clinical trials indicate that anthocyanin supplementation (typically at 320 mg/day) leads to 5–20% reductions in LDL-C^44,49 and 5–20% increases in HDL-C.^50,51 The mechanisms behind these effects likely involve inhibition of cholesteryl ester transfer protein (CETP), wherein anthocyanins suppress CETP activity, reducing the transfer of cholesterol esters from HDL to LDL/VLDL, thereby raising HDL-C and lowering LDL-C,⁴⁹ promoting cholesterol efflux, and increasing paraoxonase 1 (PON1) enzyme, i.e., important to protect HDL-C oxidation.^51,52 However, the effects on triacylglycerols (TAG) are inconsistent. While some studies report TAG reductions,^16,50 others show no change or slight increases.^52,53 This variability may stem from differences in baseline metabolic health, anthocyanin source, or study duration. Notably, short-term interventions (≤4 weeks) often fail to show significant lipid changes,⁵³ whereas longer trials (12–24 weeks) demonstrate clearer benefits.^44,50

Safety and Tolerability

In the present review, across trials, the nutraceuticals were generally well tolerated. For example, no adverse events were reported for quercetin even at a high dose of 1000 mg/day for short durations. EGCG doses up to 856 mg/day for 12 months were observed to have no negative impacts and to be well tolerated, other than mild constipation (4 subjects) and abdominal discomfort (5 subjects). Anthocyanin intake was also reported to be safe across randomized trials. Green tea, mainly EGCG, may increase the systemic circulation of several statins and calcium channel blockers and may cause drug toxicity, while reducing the bioavailability of beta-blockers may decrease the drug efficacy.^55–57 Quercetin, on the other hand, can displace warfarin from albumin binding sites, increasing its free fraction with minimal direct CYP2C9 inhibition.⁵⁸ Therefore, patients on these medications must consult their healthcare provider before consuming green tea extracts, concentrated EGCG supplements, or high-dose quercetin to ensure safe and effective treatment.

Translational and Economic Implications

These nutraceuticals are inexpensive and widely available through daily diets (e.g., green tea, onions, berries), suggesting potential for cost-effective integration into public health strategies. While preliminary cost comparisons with pharmacological interventions are encouraging, robust economic modeling is required before firm conclusions can be drawn (Table 3).

Table 3: Comparative overview of nutraceuticals: effective doses, mechanisms of action, and target populations for managing hypertension and hyperlipidemia.
Nutraceutical	Effective Daily Dose	Primary Mechanisms	Target Populations	Key Dietary Sources
Quercetin	100–200 mg (up to 500 mg for hypertension)	• ACE inhibition- SCAP-SREBP2-LDLr pathway modulation- Endothelial NO enhancement- Gut microbiota modulation	• Stage 1 hypertension- Overweight/obese individuals- Smokers	Onions and apples
EGCG	200–300 mg (up to 856 mg in trials)	• eNOS activation- Endothelin-1 suppression- LDL receptor upregulation- Antioxidant effects	• Obesity/metabolic syndrome- Postmenopausal women- Central obesity	Green tea (2–3 cups/day)
Anthocyanins	300–500 mg	• CETP inhibition- NO production enhancement- Cholesterol efflux promotion- Antiinflammatory effects	• Elderly adults- Metabolic syndrome- Postmenopausal hypertension	Berries (blueberries, chokeberries), purple grapes, plums

Conclusion, Limitations, and Future Perspectives

Regular dietary incorporation of EGCG from green tea, quercetin from onions, and anthocyanins from berries provides a promising, natural, and accessible approach to mitigating hypertension and dyslipidemia. These compounds exert complementary mechanisms, i.e., spanning vasodilation, oxidative stress reduction, ACE inhibition, improved lipid clearance, and modulation of inflammatory markers, offering comprehensive cardiovascular protection. Clinical evidence supports meaningful reductions in BP and LDL-C, with anthocyanins showing the most pronounced BP-lowering effect, quercetin delivering consistent benefits in stage 1 hypertensive individuals, and EGCG offering broad metabolic improvements in obese or metabolically compromised populations. Clinical evidence suggests optimal daily doses of 100–200 mg for quercetin, 200–300 mg for EGCG, and 300–500 mg for anthocyanins, with longer durations (≥8 weeks) yielding more consistent benefits.

Importantly, their integration into common dietary items such as breakfast drinks, salads, and juices leverages culturally acceptable eating patterns, potentially enhancing adherence. Economically, these nutraceuticals can be obtained from low-cost, locally available foods, representing a sustainable alternative or adjunct to pharmacotherapy, with the potential to alleviate the economic burden of CVD treatment. Current evidence on these nutraceuticals faces challenges due to inconsistent study designs, including small participant groups and short trial durations (typically under 12 weeks). Additionally, results vary depending on whether compounds were tested as purified supplements or whole-food sources. To establish clear guidelines, rigorous long-term studies with standardized protocols and larger, diverse populations are urgently needed.

References

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Cite this article as:
Qamar M, Ismail E, Khan MZ, Fatim BI, Din MJU and Abbas WM. Nutraceuticals Against the Silent Killers: Role of Secondary Metabolites in the Prevention and Management of Hypertension and Hyperlipidemia. Premier Journal of Cardiology 2025;5:100013

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