Queen Bee Acid: Facilitates Neurogenesis and Activates AMPK

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Royal Jelly

Royal jelly is a honey bee secretion that is used in the nutrition of larvae and adult queen bees.

It is secreted from the glands in the hypopharynx of worker bees, and fed to all larvae in the colony.  The composition of royal jelly includes:

  • water  67%
  • crude protein  12.5%
  • free amino acids
  • simple sugars (monosaccharides)  11%
  • fatty acids  5%
  • trace minerals
  • enzymes
  • antibacterial and antibiotic components
  • pantothenic acid (vitamin B5)
  • pyridoxine (vitamin B6)
  • vitamin C
  • AMP N1-oxide  1 
  • acetylcholine  2 

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Figure 1.  Developing queen larvae surrounded by royal jelly

Royalactin – Protein in Royal Jelly

The queen bee is fed royal jelly exclusively and as a result causes the queen bee to become larger than the worker bees.  It is speculated that a single protein called royalactin is responsible for the unique development and size of the queen bee.

Researchers determined that only royal jelly with an addition of royalactin caused the larvae to become queen bees.  3 

Royalactin plays a central role in this process by switching on the epidermal growth factor (EGF) receptor signaling pathway which ultimately leads to epigenetic changes and a long-lived queen phenotype.

Recently it was shown that royalactin by itself also extends lifespan in Drosophila melanogaster.  4

A study from 2014 demonstrated that royalactin extends lifespan of this nematode and that both EGF (LIN-3) and its receptor (LET-23) are essential to this process. They showed that royalactin enhances locomotion in adult nematodes, implying that royalactin also influences healthspan, suggesting that royalactin is an important lifespan-extending factor in royal jelly and acts by promoting EGF signaling in C. elegans.  5

Specific Fatty Acids in Royal Jelly

Researchers have identified a number of fatty acids contained in royal jelly, including:

  • 10-Hydroxy-2-Decenoic Acid  (10-HDA; about 2 – 3%)
  • 2-Decendioic Acid
  • 10-Hydroxydecanic Acid
  • 10-Hydroxydecenoic Acid
  • P-Hydroxybenzoic Acid
  • 24-Methylenecholesterol
  • 2-Decendioic Acid
  • 10-Hydroxydecanic Acid
  • 10-Hydroxydecenoic Acid
  • P-Hydroxybenzoic Acid
  • Sebacic acid

10-hydroxy-2-decenoic acid (10-HDA) – Queen Bee Acid

The main fatty acid in royal jelly is 10-hydroxy-2-decenoic acid (10-HDA), consisting of about 2 to 3% by volume. 

It is also known as Queen Bee acid.

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Figure 2.  10-hydroxy-2-decenoic acid molecule  (Source)

Royal Jelly’s Pharmacological Activities

Royal jelly as a whole has been reported to possess a variety of pharmacological activities such as:

  • antibacterial  7
  • antitumor  8 
  • anti-allergic  9
  • anti-fatigue  10 
  • anti-inflammatory  11
  • immunomodulatory  12
  • induces neurite outgrowth  13
  • prevents dermatitis  14
  • prevents hypercholesterolemia  15
  • prevents osteoporosis  16
  • stimulates bone formation  17 
  • antioxidant activity  18
  • inhibitory effects on lipid peroxidation  19
  • antihypertensive effects  20

Specific Health Benefits of 10-hydroxy-2-decenoic acid (queen bee acid)

There are two important health benefits of 10-hydroxy-2-decenoic acid (queen bee acid) that has been identified which include:

  • facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes)
  • activates adenosine monophosphate-activated protein kinase (AMPK)

Facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes)

The birth of new brain cells (neurogenesis) continues throughout life in the brain, in particular the dentate gyrus region of the hippocampus.

The hippocampus produces roughly 700 new brain cells each day.  This corresponds to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging.

Neurogenesis is generated in two regions of the adult brain:

  • The subventricular zone (SVZ) lining the lateral ventricles
  • The subgranular zone (SGZ), part of the dentate gyrus of hippocampus

Neurogenesis can have tremendous functional significance to the healthy adult brain. In the aging adult, hippocampal function declines with potential memory dysfunction. This may due to the fact that neurogenesis is substantially reduced in the hippocampus in the aging adult.

If neurogenesis in the hippocampus continues throughout life, then one would presume that the size of hippocampus would increase in size. However, this is not the case since the rate of neuron death balances out the proliferation.

Researchers have determined that 10-hydroxy-2-decenoic acid (10-HDA) facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes).  21

10-hydroxy-2-decenoic acid (10-HDA) significantly increased the percentage in the total cell population of not only neurons immunoreactive for class III beta-tubulin (Tuj1) but also astrocytes immunoreactive for glial fibrillary acidic protein (GFAP), and oligodendrocytes immunoreactive for 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) generated from NSCs, but decreased that of nestin-positive NSCs.

Resaerchers concluded that 10-hydroxy-2-decenoic acid (10-HDA) facilitates neurogenesis.

Activates adenosine monophosphate-activated protein kinase (AMPK)

AMPK (adenosine monophosphate-activated protein kinase) is an enzyme contained in every cell of the human body that serves as the body’s master regulating switch.

When the AMPK master switch is turned “ON” (by activating AMPK), it inhibits multiple damaging factors of aging and enables cells to become revitalized.  Scientists have found that activated AMPK promotes longevity factors that have been shown to extend life span in numerous organisms.  22 23

There are various studies that show an increase in AMPK supports:

  • Reduced fat storage 24
  • New mitochondria production 25
  • Promotion of healthy blood glucose and lipids already within normal range 26

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Figure 3.  Roles of AMPK in the control of whole-body energy metabolism. Notes: Activation of AMPK (green lines) stimulates the energy-generating pathways in several tissues while inhibiting the energy-consuming pathways (red lines). In skeletal muscle and heart, activation of AMPK increases glucose uptake and fatty acid oxidation. In the liver, AMPK activity inhibits fatty acid and cholesterol synthesis. Lipolysis and lipogenesis in adipose tissue are also reduced by AMPK activation. Activation of AMPK in pancreatic β-cells is associated with decreased insulin secretion. In the hypothalamus, activation of AMPK increases food intake.  Source: AMPK activation: a therapeutic target for type 2 diabetes? Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, and Asish K Saha, Diabetes Metab Syndr Obes. 2014; 7: 241–253. Published online 2014 Jun 24. doi: 10.2147/DMSO.S43731

A study from October 2013 determined that queen bee acid activates AMP-activated protein kinase (AMPK) and enhances glucose uptake in skeletal muscle in in vivo testing in mice, and in vitro testing using myotubes.  27 

Researchers treated L6 myotubes with various medium chain fatty acids and showed that 10-hydroxy-2-decenoic acid (10-HDA) administration resulted in a significant increase in phosphorylated AMPKα. 10-hydroxy-2-decenoic acid (10-HDA) activates AMPK independently of insulin and significantly increased glucose uptake into L6 myotubes following translocation of glucose transporter 4 (Glut4) to the plasma membrane (PM). The activation was induced by the upstream kinase Ca²⁺/calmodulin-dependent kinase kinase β, but was independent of changes in AMP:ATP ratio and the liver kinase B1 pathway.