Apigenin (from Citrus grandis Fruit Extract)

Apigenin Common Name


Top Benefits of Apigenin

  • Supports mitochondrial function and cellular energy*
  • Supports exercise performance*
  • Supports metabolism*
  • Supports healthy weight*
  • Supports antioxidant defenses*
  • Supports healthy cellular responses*
  • Supports cardiovascular function*
  • Supports brain function*
  • Supports kidney health*
  • Supports healthy gut microbiota* 

What is Apigenin?

Apigenin belongs to the flavone class of flavonoids. It is one of the more common flavones in the diet, found in many fruits and vegetables, including celery and parsley. It is found in very high amounts in the flowers used to make chamomile tea. Apigenin has been reported to support cardiovascular, brain, and kidney function, and metabolic benefits. It indirectly boosts NAD+ by modulating the activity of the CD38 NAD+-consuming pathway. Apigenin is also supportive of antioxidant defenses and the mitochondrial cellular energy network.

Neurohacker’s Apigenin Sourcing

Citrus grandis (i.e., pomelo) fruit extract was selected as an ingredient to provide a standardized amount of apigenin. Pomelo is one of the original ancestral citrus fruits from which all modern cultivated citrus varieties originated. They are consumed as a fruit throughout Southeast Asia. A pomelo is somewhat similar in appearance to a large grapefruit. This is because grapefruits originated as a back-cross of pomelo and sweet orange. Peels of pomelo (or grapefruits) are often used to produce the apigenin found in dietary supplements.

Apigenin Dosing Principles and Rationale

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. Because of this, we don’t think of flavones like apigenin as being “more is better” ingredients. Instead we think it’s better to use them following hormetic dosing principles (see Neurohacker Dosing Principles). Because of this we use a low dose of apigenin. 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).

Apigenin Key Mechanisms 

Mitochondrial biogenesis

  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) [1]
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (TFAM) [1]
  • Upregulates mitochondrial size/density/number  [1]

Mitochondrial function

  • Protects from mitochondrial dysfunction [1,2]
  • Upregulates electron transport chain and oxidative phosphorylation proteins/genes (supports ATP production) [1,3]
  • Protects from complex I-V inhibition [2,4]
  • Supports NAD+ generation - inhibits CD38 [5]
  • Upregulates citric acid cycle proteins/genes [3]

Signaling pathways

  • Upregulates AMP-activated protein kinase (AMPK) [1,6–11]
  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) [5,8,23 12,13]
  • Upregulates liver kinase B1 (LKB1) [9]

Exercise performance (ergogenic effect)

  • Supports endurance performance [1] 
  • Supports muscle structure/function [1]


  • Supports healthy blood glucose levels [1,3,5,12,14]
  • Supports healthy insulin sensitivity [1,3]
  • Upregulates fatty acid metabolism proteins/genes [3]
  • Supports β-oxidation (fatty acid metabolism) [5]

Body weight 

  • Downregulates fat accumulation and blood/liver lipid levels [1,3,6,13,14]
  • Downregulates adipocyte differentiation and lipid accumulation [7]
  • Downregulates adipogenesis - downregulates peroxisome proliferator-activated receptor gamma (PPARγ) [3]
  • Upregulates lean mass [1]

Cellular signaling 

  • Downregulates the expression of proinflammatory cytokines – tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), IL-6 [1,3,13,15,16]
  • Downregulates nuclear factor NF-κB signaling [4,13–15]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [12–14,16–19]
  • Downregulates the generation of reactive oxygen species [2,8,17]
  • Replenishes glutathione (GSH) levels [12,13,17,18]

Cardiovascular function

  • Supports ECG parameters, hemodynamics, and left ventricular function [12]
  • Protects from cardiac injury and dysfunction [4,12,20]
  • Protects from vascular damage [2,14]
  • Supports healthy vascular function [6,8]
  • Supports healthy blood pressure  [8]
  • Supports healthy cholesterol levels [6,14]

Brain function

  • Neuroprotective effects [16,17]
  • Protects cognitive function [18]
  • Downregulates amyloid-beta accumulation [18] 

Gut microbiota

  • Regulates the composition of the gut microbiota [21,22]
  • Modulates gut microbial gene expression [22]

Healthy aging and longevity

  • Upregulates SIRT-1  [8]
  • Downregulates mTOR signaling [9,11,15,20,23,24]
  • Upregulates insulin-like growth factor-1 (IGF-1) signaling [25,26]


[1] Choi WH, et al. Mol Nutr Food Res. 2017;61(12). doi:10.1002/mnfr.201700218
[2] Duarte S, et al. Int J Mol Sci. 2013;14(9):17664-17679. doi:10.3390/ijms140917664
[3] Jung UJ, et al. Nutrients. 2016;8(5). doi:10.3390/nu8050305
[4] Cardenas H, et al. Int J Mol Sci. 2016;17(3):323. doi:10.3390/ijms17030323
[5] Escande C, et al. Diabetes. 2013;62(4):1084-1093. doi:10.2337/db12-1139
[6] Wong TY, et al. Biomed Pharmacother. 2017;96:1000-1007. doi:10.1016/j.biopha.2017.11.131
[7] Ono M, Fujimori K. J Agric Food Chem. 2011;59(24):13346-13352. doi:10.1021/jf203490a
[8] Wei X, et al. Clin Sci . 2017;131(7):567-581. doi:10.1042/CS20160780
[9] Tong X, et al. Mol Carcinog. 2012;51(3):268-279. doi:10.1002/mc.20793
[10] Zang M, et al. Diabetes. 2006;55(8):2180-2191. doi:10.2337/db05-1188
[11] Bridgeman BB, et al. Cell Signal. 2016;28(5):460-468. doi:10.1016/j.cellsig.2016.02.008
[12] Mahajan UB, et al. Int J Mol Sci. 2017;18(4). doi:10.3390/ijms18040756
[13] Wang F, et al. Chem Biol Interact. 2017;275:171-177. doi:10.1016/j.cbi.2017.08.006
[14] Ren B, et al. Eur J Pharmacol. 2016;773:13-23. doi:10.1016/j.ejphar.2016.01.002
[15] Kim A, Lee CS. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(3):271-283. doi:10.1007/s00210-017-1454-4
[16] Zhang F, et al. Neurol Sci. 2014;35(4):583-588. doi:10.1007/s10072-013-1566-7
[17] Han Y, et al. J Clin Neurosci. 2017;40:157-162. doi:10.1016/j.jocn.2017.03.003
[18] Zhao L, et al. Molecules. 2013;18(8):9949-9965. doi:10.3390/molecules18089949
[19] Nielsen SE, et al. Br J Nutr. 1999;81(6):447-455.
[20] Yu W, et al. Evid Based Complement Alternat Med. 2017;2017:2590676. doi:10.1155/2017/2590676
[21] Li L, Somerset S. Nutrients. 2018;10(9). doi:10.3390/nu10091264
[22] Wang M, et al. Molecules. 2017;22(8). doi:10.3390/molecules22081292
[23] Stump TA, et al. J Pharm Pharmacol. 2017;69(7):907-916. doi:10.1111/jphp.12718
[24] Yang J, et al. Biomed Pharmacother. 2018;103:699-707. doi:10.1016/j.biopha.2018.04.072
[25] Babcook MA, Gupta S. ACurr Drug Targets. November 2012. PMID: 23140291.
[26] Shukla S, et al. Pharm Res. 2012;29(6):1506-1517. doi:10.1007/s11095-011-0625-0