Endothelial and Cardiovascular Effects of Naringin

DavidPS

I was quite surprised by the wide range of naringin concentration in the different varieties of citrus. The mandarin orange has over 161X as much naringin as the valencia orange.

Endothelial and Cardiovascular Effects of Naringin: A Systematic Review (2025)
https://www.mdpi.com/2072-6643/17/16/2658#

Methods: The review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Scopus, EMBASE, and Web of Science databases was performed using key terms including “naringin”, “cardiovascular”, “endothelial function”, “atherosclerosis”, and “ischemia-reperfusion.” A total of 62 studies were included and categorized into three domains: cellular models, animal studies, and human trials. Risk of bias assessments were conducted for each study type using appropriate tools.

Results: Naringin consistently exhibited antioxidant, anti-inflammatory, and vasoprotective effects across all study types. Mechanistic studies highlighted the modulation of key signaling pathways, including PI3K/Akt, NF-κB, Nrf2, the renin-angiotensin system (RAS), and enhancement of KATP channel expression, as well as its ability to inhibit apoptosis, autophagy, and ferroptosis. In animal models, naringin improved endothelium-dependent vasorelaxation, reduced infarct size, and preserved myocardial function. Although limited, human trials reported beneficial effects on lipid profiles, arterial stiffness, and adiponectin levels.

Conclusions: Naringin demonstrates strong potential as a dietary adjunct for cardiovascular protection, especially in the context of ischemic injury and vascular dysfunction. Further well-designed clinical trials are needed to define optimal dosing strategies and improve its bioavailability in humans.

otto

Not all oranges are created equal.

LucH

@DavidPS
Hi,
I know that citrus is a good source of antioxidants, well appreciated for nephro-, hepato-, neuro-problems, etc. Right. I have no problem with these statements.
But after reading the whole study (1) and analyzing the pdf, an alarm bell went off when I read that we weren't just talking about naringin, but also furocoumarin. It's well established that grapefruit is very rich in coumarin. Coumarin has an impact on the management of the detox pathway. It's a question of quantity and frequency.
High amount of naringine in mandarins
If we observe the amount of naringine (2) from the same study, I’ll highlight these usual fruits, often consumed in a high frequency and sometimes in high level when taken in cure. Mind if in a smoothie (combination with celery + other flavonols). Still a question of frequency.
1 Citrus (x.) sinensis 21.3 mg/ml (orange fruit, navellina type)
2 Citrus clementina 8 (Clementine)
3 Citrus reticulata 3383.6 (mandarin)
4 Citrus paradisi 230 (grapefruit)

NB: Observe the quantity of naringin found (mg/ml) in grapefruit / citrus paridisi (230 mg/ml), and especially between clementine / citrus clementina (8 mg) and mandarin / Citrus reticulata (3383.6 mg).
3383 mg/ml naringin in a mandarin !!!
I, who avoided the orange fruit for breakfast and had one or two clementines or a mandarin, depending on what I could find while shopping (less histamine reaction with a mandarin (H2) than with an orange (H3 and L3), I will review my approach (impact on the Cyp450 pathway, in case of detox). Now, more alternation has to be planned (because of the extended half-life, longer than I thought).
Note that everyone won’t react on the same way, depending on processing capacity (liver and kidneys).
Duality Explained
Naringin prevents / interferes with an enzyme during the metabolism of many medications, resulting in an increase in their concentration in the blood...
One grapefruit (fruit) a week will do the trick. Not if it's a glass of fruit juice, when you're taking certain medications. And the list of molecules is quite long. See reference (3) and details on my forum (4) for a more thorough analysis.
Detox pathway CYP450: shortly explained
Our body metabolizes (breaks down) foreign substances that enter it, whether by consuming natural plant toxins contained in food (with reaction of the defense system, as with lectins, for example) or when we are exposed to toxic substances (pesticide residues, air pollution, or skin care products).
Our detoxification genes operate at different rates due to genetic variations. This means that we are not all equal when it comes to eliminating toxins. Please understand that we do not eliminate at the same rate.
Diagram of toxin elimination pathways (2 main phases) (5)
Phase 1: Preparation & Neutralization of the molecule's toxicity
Phase 2: Conjugation / modification to facilitate elimination (improved fluidity => more hydrophilic).
Certain nutrients are required to optimize these two phases to facilitate excretion by the body, mainly by the kidneys via urine and by bile in the feces.

Sources and References:

Meticulous parade on naringin respecting its pharmacological activities and novel formulations. DOI : 10.22038/ajp.2022.20001 AJP India, 2022. Mahboob Alam et al.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9516400/pdf/AJP-12-457.pdf
Figure: Table 1. Total content of naringin in different citrus fruits. Alam et al. 2014
S.N. Citrus species Naringin content (mg/ml) Reference
Amount of naringin in different species of the citrus family
1 Citrus (x.) sinensis 21.3 (orange, navellina, white, or blood orange varieties). Navellina and amara are the best known.
2 Citrus bergamia 22.3 (lemon)
3 Citrus clementina 8 (Clementine, hybrid between orange and mandarin)
4 Citrus reticulata 3383.6 (mandarin)
5 Citrus paradisi 230 (grapefruit)
6 Citrus aurantium 19.7 (orange, amara variety)
7 Fruit juices/citrus juices (Naringin) 15.6
8 Grapefruit, raw, red and pink (C. paradisi) (naringenin) 32.6
9 Grapefruit, pure juice 30-50
10 Pummelo, pure juice 84.8
11 Tangelo (hybrid between mandarin and grapefruit). High levels of neohesperidin and, to a lesser extent, naringin.
12 Minneola (hybrid of a grapefruit and a tangerine). Less naringin than sour oranges but more than sweet oranges.
Source: From the same reference N° 1. DOI : 10.22038/ajp.2022.20001 (for 1-10)
Table Drugs & CyP450 interference
http://www.anaesthetist.com/physiol/basics/metabol/cyp/Findex.htm
Is your Breakfast Hiding a Detox Disruptor? (in French, translator needed, but with English sources).
Citrus Fruits & Enzymes: When 2 Mandarins Are Enough to Disrupt Your Liver!
https://mirzoune-ciboulette.forumactif.org/t2126-agrumes-enzymes-quand-2-mandarines-suffisent-a-brouiller-votre-foie#30299
Background:
Citrus naringin impacts the Cyp450 detox pathway, thus influencing enzymatic efficacy, which can contribute to exacerbating the toxicity due to accumulation (half-life) of certain medications or supplements, or even simply the elimination of caffeine or theine.
Moreover, regularly eating two mandarins for breakfast could trigger melanoma in people sensitive to UV rays.
NB: This is just a teaser. The goal is to make you aware that you should alternate the type of citrus fruit you eat, if not limited to the winter season.
Detox pathway explained (In French)
https://mirzoune-ciboulette.forumactif.org/t1609-voie-de-detoxification-cyp450?highlight=Detox+pathway
See figure “Liver detoxification” for useful nutrients (in English)

Phase 1: Foods and Nutrients useful for balancing, in phase I (neutralization).
Phase 2: Foods and Nutrients useful for evacuating, in phase II (feces and urine).

Luke

@otto said in Endothelial and Cardiovascular Effects of Naringin:

Not all oranges are created equal.

Sounds like comparing mandarin oranges to valencia oranges is like comparing apples to oranges.

DavidPS

@LucH - thanks for your analysis. I tend to underthink some of these studies and often I do not make connections to other studies.

I stopped eating grapefruit moths ago but I had not given a second thought to eating mandarin oranges. I am goig to rethink my dietary sources of Vitami C.