Sweet Orange | Blood orange
Supports body clock function (i.e., circadian system)
Supports healthy weight *
Supports mitochondrial biogenesis, structure, and function *
Supports healthy metabolism and insulin signaling *
Supports cellular responses and antioxidant defenses *
Supports brain function *
Supports the protection of organs and systems *
Supports healthy gut microbiota *
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.*
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.
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 Neurohacker 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 dosage (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 dose accordingly.*
Supports circadian rhythms*
Nobiletin and tangeretin are clock amplitude-enhancing small molecules (CEM) — modulate the circadian system [1,2]
Nobiletin and tangeretin support circadian rhythm protein Period 2 (PER2) [1–3]
Promotes metabolic function through a circadian-dependent mechanism [1,4]
Supports mitochondrial biogenesis*
Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling [4–7]
Supports nuclear transcription factors of mitochondrial biogenesis (nuclear respiratory factor 1 [NRF1], NRF2, mitochondrial transcription factor A [TFAM]) [6,8–10]
Supports mitochondrial structure and function*
Supports mitochondrial function [11,12]
Supports complex I-V function [4,13]
Supports ATP production 
Supports mitochondrial membrane potential 
Supports signaling pathways*
Supports AMP-activated protein kinase (AMPK) signaling [4,8,15,16]
Supports peroxisome proliferator-activated receptor alpha (PPARα) and delta PPARδ [6,8,17–19]
Supports PPARγ signaling [6,15,17–20]
Influences glycogen synthase kinase 3 beta (GSK-3β) [4,13,21]
Influences mTOR signaling 
Supports SIRT1 signaling [4,6]
Supports healthy metabolic function*
Supports healthy blood glucose levels [1,5,7,17,18,22]
Supports healthy insulin sensitivity [1,4,5,7,18,19,22]
Supports GLUT1 and GLUT4 glucose transporter function [17,18]
Supports a balanced respiratory quotient 
Supports the urea cycle 
Promotes healthy body weight*
Supports healthy body weight [1,5,7,17,22]
Supports healthy blood and liver lipid levels [1,5,7,19,22,24]
Supports healthy blood triglyceride and cholesterol levels [7,19,24,25]
Supports adiponectin levels [17,18]
Promotes the differentiation of brown adipose tissue [6,22]
Supports UCP-1 and UCP-2 [6,7,17,22]
Promotes thermogenesis 
Supports cellular signaling*
Supports healthy immune signaling [7–10,17–21,26–28]
Supports immune cell activity [7,29]
Supports antioxidant defenses*
Supports antioxidant defenses [8,9,12,27]
Counters the generation of reactive oxygen species (ROS) [4,8,11,12,27]
Replenishes glutathione (GSH) levels [8,9,12,27]
Supports heme oxygenase-1 (HO-1)levels [10,20]
Supports brain function*
Supports neuroprotective functions [9,11,12,21,30–32]
Supports cognitive function [3,13,33]
Supports emotional memory 
Supports healthy neural cytokine signaling [26,28]
Supports hippocampal mitochondrial bioenergetics 
Supports BDNF signaling [31,35]
Supports healthy organ and system function*
Supports healthy cardiovascular structure and function [5,7,36–38]
Supports healthy liver structure and function 
Supports healthy gastrointestinal structure and function 
Supports a healthy gut microbiota*
Supports a healthy gut microbiota composition [39–42]
Supports healthy gut microbial metabolism 
Supports gut barrier function 
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, cure, or prevent any disease.
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