Citrus sinensis L. Fruit Extract (40% nobiletin)

Citrus × sinensis, which includes sweet oranges and blood oranges, is regularly consumed in the diet. The peels and fruit are a rich source of the polymethoxylated flavones nobiletin and tangeretin. They also contain the flavanone hesperidin and lesser amounts of other citrus bioflavonoids. Citrus bioflavonoids were once called vitamin P and have been used to support healthy blood vessels and veins. Flavonoids tend to promote antioxidant defenses and a balanced cellular response. Citrus flavonoids share these properties. This citrus bioflavonoid extract has been concentrated for the unique polymethoxylated flavone nobiletin, a clock-enhancing small molecule used to support body clock function and metabolic health.*

Top Benefits of Citrus bioflavonoids

Supports body clock function (i.e., circadian system)*

Supports healthy metabolism*

Supports brain function*

Supports healthy gut microbiota*  

Qualia’s Citrus bioflavonoids Sourcing

A Citrus × sinensis extract standardized for 40% nobiletin was selected because this unique polymethoxylated flavone is a modulator of clock function (i.e., circadian system). 

The immature dried fruit of Citrus × sinensis is used as a source for nobiletin. In addition to a standardized amount of this polymethoxylated bioflavonoid, the dried fruit contains a range of other citrus bioflavonoids.

This standardized extract is supplied by Brewster Nutrition, a leader in citrus bioflavonoids since 1950. The 40% standardized extract is their highest concentration for nobiletin. It’s an expensive ingredient, but worth it.

Citrus bioflavonoids Formulating Principles and Rationale

Many flavonoid molecules are part of plants’ protective responses to mild environmental stress. Consuming them tends to produce adaptive functional responses, upregulating pathways that provide stress resistance. We think of polymethoxylated flavones like nobiletin and citrus bioflavonoids in general as having threshold effects. When combined with other flavonoids we think it’s better to use them following hormetic dosing principles (see Qualia Dosing Principles). Flavonoids are additive, and often complementary with other polyphenol compounds, so the combination of all polyphenols in a formulation should be considered when determining serving size (not the amount of a single polyphenol molecule in isolation). When we dose Citrus × sinensis we consider the content of other polyphenols in the formulation and adjust the serving accordingly.*

Citrus bioflavonoids Key Mechanisms

Supports circadian rhythms*

Supports the activity of the circadian system* [1–3]

Supports metabolic function through a circadian-dependent mechanism* [1,4]

Supports mitochondrial function*

Supports healthy mitochondrial function [5,6]

Supports electron transport chain activity and ATP production* [4,7,8] 

Supports the activity of transcription factors of mitochondrial biogenesis (PGC-1α)* [4,9–11]

Supports signaling pathways*

Supports AMPK signaling* [4,12–14]

Influences mTOR signaling* [15]

Supports SIRT1 signaling* [4,10]

Supports PPARα, PPARδ, and PPARγ signaling* [10,12,14,16–19]

Influences GSK-3β activity* [4,7,15]

Promotes healthy metabolism*

Supports maintenance of healthy blood glucose levels* [1,9,11,16,17,20]

Supports healthy body composition* [1,9,11,16,20]

Supports maintenance of healthy blood and liver fat levels* [1,9,11,18,20,21]

Supports maintenance of healthy blood triglyceride and cholesterol levels* [11,18,21,22]

Supports adiponectin levels* [16,17]

Supports the differentiation of brown adipose tissue and thermogenesis* [10,20]

Supports UCP-1 and UCP-2 activity* [10,11,16,20]

Helps balance the respiratory quotient* [1]

Supports a healthy urea cycle* [23]

Supports antioxidant defenses*

Supports antioxidant defenses* [6,14,24,25]

Counters ROS production and oxidative stress* [4–6,14,25]

Supports Nrf2 signaling and phase II antioxidant defenses* [14,19,24,26]

Supports brain function*

Supports neuroprotective functions* [5,6,15,24,27–29]

Supports cognitive function (in animals)* [3,7,30,31]

Supports neural immune signaling* [32,33]

Supports hippocampal mitochondrial bioenergetics* [8]

Supports BDNF signaling* [28,34]

Supports healthy stress hormone levels* [35–42]

Promotes general health*

Supports healthy cardiovascular structure and function* [9,11,43–45]

Supports healthy liver structure and function* [14]

Supports healthy gastrointestinal structure and function* [25]

Supports healthy immune cell activity* [11,46]

Supports healthy immune signaling* [11,14–19,24–26,32,33]

Supports a healthy gut microbiota*

Supports healthy gut microbiota composition* [47–50]

Supports healthy gut microbial metabolism* [49]

Supports gut barrier function* [47]

Complementary ingredients*

Citrus bioflavonoids support bioavailability and the accumulation of vitamin C in some tissues* [51–55]

Citrus bioflavonoids may be needed to support some of Vitamin C’s functional benefits* [56–58]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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