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Citrus Viride

Q: Is Citrus viride supplementation safe?

Yes, based on extensive data for citrus flavonoids, it is generally considered safe with a low incidence of mild side effects, primarily gastrointestinal discomfort.

Q: How long before benefits appear?

Improvements in endothelial function and reductions in inflammation have been observed within weeks to a few months of consistent supplementation.

Q: Can it replace medications?

No, Citrus viride or its flavonoids should not replace prescribed medications. It may serve as an adjunctive supplement to support health.

Q: Are the benefits dose-dependent?

Yes, research indicates a dose-response relationship, particularly for improvements in endothelial function, with higher doses showing greater effects within safe limits.

Also known as: Citrus viride, lime, sour orange, citrus flavonoids, polyphenolic plant extracts, hesperidin, nobiletin

Overview

Citrus viride is a species within the Citrus genus, closely related to other citrus fruits like bitter orange and sweet orange. It is rich in bioactive flavonoids, primarily hesperidin and nobiletin, found in its peel and pulp. Supplements derived from Citrus viride or its isolated flavonoids are categorized as citrus flavonoids or polyphenolic plant extracts. They are primarily investigated for their potential to reduce cardiovascular disease risk factors, improve endothelial function, exert anti-inflammatory effects, and support liver health. While direct research on Citrus viride as a whole is limited, extensive high-quality evidence, including systematic reviews and meta-analyses, supports the benefits of its key flavonoid components, hesperidin and nobiletin, for their antioxidant, anti-inflammatory, and metabolic regulatory properties.

Benefits

Citrus viride, primarily through its flavonoid content, offers several evidence-based benefits. For cardiovascular health, hesperidin supplementation significantly reduces cardiovascular disease risk factors. A meta-analysis of RCTs (n=596) showed citrus flavonoid supplementation increased flow-mediated vasodilation (FMD) by 2.75% (95% CI: 1.29, 4.20; p < 0.001), a clinically meaningful improvement in endothelial function. Each 200 mg/day increase in citrus flavonoids improved FMD by 1.09%. Hesperidin also demonstrates anti-inflammatory and metabolic effects, reducing blood pressure and inflammatory markers in type 2 diabetes patients. Nobiletin, another key flavonoid, shows promise in preclinical studies for improving liver function by reducing oxidative stress, inflammation, and insulin resistance, and modulating Nrf2 and AMPK pathways, though clinical trials are still needed. These benefits are most studied in populations with cardiovascular risk factors, type 2 diabetes, and liver disease models. Most RCTs range from weeks to a few months, indicating benefits can appear relatively quickly.

How it works

The beneficial effects of Citrus viride are primarily mediated by its flavonoid compounds, hesperidin and nobiletin, which act through multiple biological pathways. They exert antioxidant and anti-inflammatory effects by modulating key signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB). These flavonoids improve endothelial function by enhancing nitric oxide bioavailability, leading to better vascular health. They also influence lipid and glucose metabolism and protect hepatocytes from oxidative damage. Nobiletin, in particular, modulates AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-α), contributing to its metabolic and liver-protective actions. Citrus flavonoids have moderate bioavailability and are often metabolized by gut microbiota into active compounds.

Side effects

Citrus viride, through its flavonoid components, is generally considered safe with a low incidence of adverse effects in clinical trials. Mild gastrointestinal discomfort has been reported in some studies, but not consistently across all research. There are no significant reports of uncommon (1-5%) or rare (<1%) side effects, and no serious adverse events have been documented. Potential drug interactions may exist with medications metabolized by cytochrome P450 enzymes due to the broad effects of flavonoids, though specific data for Citrus viride are lacking. Individuals on anticoagulants or with known citrus allergies should exercise caution. There are no established contraindications, but data on safety in pregnant or lactating women are limited, so use in these populations should be approached with caution.

Dosage

Meta-analyses suggest that benefits from citrus flavonoids, such as those found in Citrus viride, can be observed at minimum effective doses starting around 200 mg/day. Optimal dosage ranges for hesperidin or equivalent citrus flavonoids used in clinical trials with positive effects typically go up to 500 mg/day. While a maximum safe dose is not well established, doses up to 800 mg/day of hesperidin have been used safely in trials. Supplementation is generally recommended daily, and the timing relative to meals is not considered critical, though it may influence absorption. For best results, extracts standardized for hesperidin or nobiletin content are preferred. Co-administration with vitamin C or other antioxidants may potentially enhance the bioavailability of these flavonoids, though no specific cofactors are strictly required.

FAQs

Is Citrus viride supplementation safe?

Yes, based on extensive data for citrus flavonoids, it is generally considered safe with a low incidence of mild side effects, primarily gastrointestinal discomfort.

How long before benefits appear?

Improvements in endothelial function and reductions in inflammation have been observed within weeks to a few months of consistent supplementation.

Can it replace medications?

No, Citrus viride or its flavonoids should not replace prescribed medications. It may serve as an adjunctive supplement to support health.

Are the benefits dose-dependent?

Yes, research indicates a dose-response relationship, particularly for improvements in endothelial function, with higher doses showing greater effects within safe limits.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC11399677/ – This systematic review and meta-analysis evaluated the effects of hesperidin extracts on cardiovascular risk factors. It found significant improvements in endothelial function, specifically an increase in flow-mediated vasodilation (FMD) by 2.75%, and identified a dose-response relationship. The study highlights the moderate to high quality of evidence, though notes limitations such as heterogeneity and short intervention durations.
https://pubmed.ncbi.nlm.nih.gov/38561995/ – This source likely refers to the same meta-analysis as the previous one, focusing on the impact of citrus flavonoid supplementation on cardiovascular health. It reinforces the finding of improved endothelial function (FMD) and suggests that citrus flavonoids can be beneficial for reducing cardiovascular disease risk factors.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1354809/full – This review article summarizes preclinical evidence for nobiletin, a flavonoid from citrus peel, in the context of liver disease. It identifies multiple molecular targets and beneficial effects on liver function, including reduction of oxidative stress, inflammation, and insulin resistance, while emphasizing the need for high-quality clinical trials to confirm these findings in humans.
https://pdfs.semanticscholar.org/4ab9/41317936026014b47467f1de0d298d258e80.pdf – This source, likely a review or research paper, contributes to the broader understanding of citrus flavonoids. It likely discusses their general safety and efficacy in improving vascular function and reducing inflammation, consistent with findings across various populations with cardiovascular risk factors, while also acknowledging limitations like variability in flavonoid sources and doses.