Sunday, April 14, 2013

Royal Jelly for Neurogenesis

I'm always on the lookout for a safe way to help our children generate more brain cells (neurogenesis). It's important to support neurogenesis for this population because, in the aging brains of people with Down syndrome, it's been found that self-destruction of brain cells (apoptosis) occurs more quickly than it should (some apoptosis is okay and normal).

Apoptosis has been associated with the gradual loss of neurons (nerve and brain cells) called neurodegeneration. Neurodegeneration causes impairments in general growth and involves disturbances with immunity, in the heart and increases some cancer risks. (See Apoptosis in Down's syndrome for details.)

Apoptosis occurs in those with DS because they produce too many glial cells. The glial cells are
non-neural cells that perform "housekeeper" functions such as clearing out debris and excess materials -- too much of them kills too many brain cells. Meanwhile, neuronal cells regenerate brain cells. So, we want to look for something that increases neuronal cells while decreasing glial cells... And that's what Royal Jelly does! (Unlike fluoxetine/Prozac, which increases glial cells... perhaps causing more neuronal death?)
I've been using Wild Blueberry Extract, Longvida Curcumin and Gingko to support Jett's neurogenesis. Recently, Royal Jelly caught my eye and I found a lot of studies supporting its use for regenerating neurons. Next, I will be researching the probiotic, bifidobactrium and the mineral, lithium for their neurogenerating properties.

Some Benefits
  • improves memory
  • invigorates mental acuity
  • increases neurogenesis 
  • improves impaired cognitive learning and motor function
  • has neurotrophic and/or neuroprotective roles 
  • promotes healthier socialization 
You can read lots (19 pages) about the great benefits of RJ here:

My Notes

Do watch for any allergic reaction since many people are sensitive to bees and bee products. First, I put it on the inside of my wrist and my husband's wrist to see if we had any reaction. Then we both tried it orally and had no reaction. I then put it on Jett's wrist and when no reaction was present, I gave him a tiny bit and increased it until I got to the full dose (see dosage below).

I give it on an empty stomach, first thing in the morning and then again right after his nap. I mix it in water with the other supplements he needs on an empty stomach. I put the royal jelly, which is in honey, on the lip of the cup so that when he drinks, the water catches the honey. He calls it "honey water" and even requests it in the morning.   

After Jett's was on RJ for a month, I don't know the specific changes that I can attribute directly to it, but I can say that Jett is continuing to progress cognitively very well. At 2 1/2, he can read anything, as fast as you can; knows his colors and shapes; recognizes number 0-100; counts spontaneously and correctly; seems to know the value of number 1-7; can "write" the correct letter shapes in the air, not completely from memory; and we recently discovered that he can tell you what a word is (up to 5 letters) if you spell it out loud.

At three years old, about three months on RJ, his language and sociability have increased greatly. He's speaking in full sentences (She's standing on her own!") some paragraphs ("Mommy's dress. It's pretty! It has snakes and alligators...") (Actually, it was a nightgown and it had paisley and squiggly lines.) and while still using one word sentences such as when requesting a "drink." In the past two months, he's started to hug and kiss us spontaneously. He didn't do this before. 

How it Works

The first study, see below (Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro), shows that royal jelly and its components (10-hydroxy-2-decenoic acid [HDEA], in particular) promote the generation of neuronal but decreased glial generation and may stimulate neurogenesis in the mature brain. (A part of the Royal Jelly does stimulate some glial cells.)

The central nervous system which includes brain and spinal cord is composed of three kinds of cells: neurons, astrocytes and oligodendrocytes. Neural stem cells have a self-renewal capacity and the ability to change into neurons, astrocytes and oligodendrocytes during brain development. Besides being present in the developing embryonic brain, neural stem cells are also found in the adult forebrain where they constantly produce smaller (progenitor) cells, and turn into neurons, suggesting that the injured brain has the capacity for self-repair. 

Excerpt from Royal jelly mental clarity at any age
RJ also contains acetylcholine which may be responsible for improving memory and invigorating mental acuity. Acetylcholine is a major neurotransmitter that determines brain processing speed and memory. It encourages brain growth by stimulating neural stem cells, and glial cells (1), which protect the brain’s neurons. Glial cells make up 90 percent of the brain's cells and perform many important functions, including: digestion of parts of dead neurons, manufacturing myelin for neurons, providing physical and nutritional support for neurons, and more(2).

Interestingly, royal jelly is the only natural rich source of pure acetylcholine (1 mg per gram). Optimal levels of acetylcholine in the brain are associated with improved memory, fluidity of thought, and enhanced cognitive function. Its high concentration of phospholipids assists people dealing with impaired cognitive learning, motor function, and awareness to better short-term memory and learning processes...

...An acetylcholine deficiency can result in attention deficit disorder, dementia, dry mouth, dry skin, learning disorders, speech problems, slow movement, mood swings, difficulty concentrating, carelessness, decreased creativity, verbal memory problems, memory lapses, and eventually could lead to Alzheimer’s and Parkinson’s diseases.


1 Hattori, N.; Nomoto, H.; Fukumitsu, H.; Mishima, S.; Furukawa, S. (October 2007). "Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro". Biomedical research (Tokyo, Japan) 28 (5): 261–266.
2  Hashimoto, M.; Kanda, M.; Ikeno, K.; Hayashi, Y.; Nakamura, T.; Ogawa, Y.; Fukumitsu, H.; Nomoto, H. et al (April 2005). "Oral administration of royal jelly facilitates mRNA expression of glial cell line-derived neurotrophic factor and neurofilament H in the hippocampus of the adult mouse brain Bioscience, biotechnology, and biochemistry 69 (4): 800
Blum, M.S., Novak A.F. and Taber III, 5. (1959). 10-Hydroxy-decenoic acid, an antibiotic found in royal jelly. Science, 130 : 452-453


I like these:
YS Eco Bee Farms Alive Bee Power Royal Jelly Paste -- 36000 mg - 20.3 oz

YS Eco Bee Farms Pure Royal Energizer -- 21 oz 1 teaspoon = 675 mg of royal jelly

YS Eco Bee Farms Royal Jelly Plus Bee Pollen -- 650 mg - 24 oz

But any organic product would be worth a try.

If it has actual honey in it, it's not suitable for those under age 2. But Royal Jelly is given to preemies with good results, without the honey. 

Be sure to get $10 off your first VitaCost vitamin order.

10-Hydroxy-Trans-2-Decenoic Acid isolated from royal jelly for sale: $114
Says for research purposes only


In one study, doses of 100 mg/kg to mice, lead to structural changes of the nerve. The daily dose for adults used in other studies varies between 10 and 500 mg of fresh royal jelly per day, with most human studies utilizing doses of 20 to 200 mg daily.

For the
therapeutic/medicinal use of honey bee products (apitherapy), higher doses are recommended: children 20-100 mg/day; adults: 200-500 mg/day.

Studies for Further Research
Biomed Res. 2007 Oct;28(5):261-6.

Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro.


Laboratory of Molecular Biology, Gifu Pharmaceutical University.


Neural stem/progenitor cells (NSCs) proliferate vigorously as neurospheres in medium containing basic fibroblast growth factor (FGF-2), but start differentiating into neurons, astrocytes or oligodendrocytes in FGF-2-free medium. An extract of royal jelly (RJ) 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. These results highlight a novel and outstanding property of the RJ, i.e., that it facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes). On the other hand, 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid characteristic of RJ, increased the generation of neurons and decreased that of astrocytes from NSCs. These observations suggest that RJ contains plural components that differently influence neuronal and/or glial lineages and that HDEA is one of such components of RJ that facilitates neurogenesis by NSCs.

Free full text here.
Biosci Biotechnol Biochem. 2005 Apr;69(4):800-5.

Oral administration of royal jelly facilitates mRNA expression of glial cell line-derived neurotrophic factor and neurofilament H in the hippocampus of the adult mouse brain.


Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu 502-8585, Japan.


Royal jelly (RJ) is known to have a variety of biological activities toward various types of cells and tissues of animal models, but nothing is known about its effect on brain functions. Hence, we examined the effect of oral administration of RJ on the mRNA expression of various neurotrophic factors, their receptors, and neural cell markers in the mouse brain. Our results revealed that RJ selectively facilitates the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that RJ shows neurotrophic effects on the mature brain via stimulation of GDNF production, and that enhanced expression of neurofilament H mRNA is involved in events subsequently caused by GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain through GDNF.

Full text here
Biomed Res. 2007 Dec;28(6):295-9.

AMP N1-oxide potentiates astrogenesis by cultured neural stem/progenitor cells through STAT3 activation.


Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan.


We earlier identified adenosine monophosphate (AMP) N1-oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth from cultured rat pheochromocytoma PC12 cells. In the present study, the effects of AMP N1-oxide on the proliferation and/or differentiation of cultured neural stem/progenitor cells (NSCs) were examined. As for cell proliferation, low micromolar concentrations of AMP N1-oxide or its parent compound, AMP, similarly enhanced the NSC proliferation-inducing activity of basic fibroblast growth factor (FGF-2), although neither compound tested alone affected cell proliferation. Conversely, high concentrations of AMP N1-oxide (over 20 microM) markedly suppressed cell growth even in the presence of FGF-2. However, this suppression was not observed with AMP. As for cell differentiation, AMP N1-oxide, but not AMP, increased the generation of astrocytes in a dose-dependent manner when the cells were cultured in medium lacking FGF-2. The generation of neurons or oligodendrocytes was not influenced by AMP N1-oxide. Furthermore, AMP N1-oxide increased the phosphorylation of STAT3 (signal transducer and activator of transcription 3), a transcription factor that mediates the expression of astrocytespecific genes. These results suggest that AMP N1-oxide is one of the components that facilitates astrogenesis by NSCs through activation of STAT3.
Royal Jelly Facilitates Restoration of the Cognitive Ability in Trimethyltin-Intoxicated Mice

Noriko Hattori,1,2 Shozo Ohta,1 Takashi Sakamoto,1 Satoshi Mishima,1 and Shoei Furukawa2Nagaragawa Research Center, API Co., Ltd, Nagara, Gifu 502-0071,  Japan
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Daigaku-nishi 1-25-4, Gifu 501-1196,  JapanReceived 5 July 2008; Accepted 16 March 2009Copyright © 2011 Noriko Hattori et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Trimethyltin (TMT) is a toxic organotin compound that induces acute neuronal death selectively in the hippocampal dentate gyrus (DG) followed by cognition impairment; however the TMT-injured hippocampal DG itself is reported to regenerate the neuronal cell layer through rapid enhancement of neurogenesis. Neural stem/progenitor cells (NS/NPCs) are present in the adult hippocampal DG, and generate neurons that can function for the cognition ability. Therefore, we investigated whether royal jelly (RJ) stimulates the regenerating processes of the TMT-injured hippocampal DG, and found that orally administered RJ significantly increased the number of DG granule cells and simultaneously improved the cognitive impairment. Furthermore, we have already shown that RJ facilitates neurogenesis of cultured NS/NPCs. These present results, taken together with previous observations, suggest that the orally administered RJ may be a promising avenue for ameliorating neuronal function by regenerating hippocampal granule cells that function in the cognition process.
Stimulatory Effects of Royal Jelly on the Generation of Neuronal and Glial Cells
- Expectation of Protection Against Some Neurological Disorders

Shoei Furukawa
Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical
5-6-1, Mitahora-higashi, Gifu 502-8585, Japan

Patients s
uffered from neurological disorders of the brain such as Alzheimer's disease and
Parkinson's disease have been greatly increasing with the development of an elderly society. We tested royal jelly as a practical alternative medicine for these diseases, because it is the source of the queen honey bee’s marvelous vitality and fertility, and widely known as a health food. We examined its activity on neural stem cells cultured from rat embryonic telencephalon. The royal jelly promoted generation of all three types of cells composing the central nervous system, neurons, astrocytes and oligodendrocytes. The action of 10-hydroxy-2-decenoic acid (decenoic acid), an unusual fatty acid of the royal jelly, and AMP N1-oxide, a compound newly found in the royal jellyby authors, were also examined, and we found that decenoic acid promoted neurogenesis and AMP N1-oxide, astrogliosis. These results demonstrate that several components of royal jelly differently affect the fate of neural stem cells, suggesting the unique activity of royal jelly as a whole is responsible for the summing up of the activities of its components. Therefore, royal jelly may be promising for the activation of neural stem cells in a mature brain expected to differentiate into neurons or glial cells. Recent investigations clarified a relationship between the neurogenesis in the dentate gyrus of the hippocampus and the symptoms of depression, expecting efficient use of royal jelly to activate neurogenesis. Reduction of neuronal death and an increase of neurogenesis in Alzheimer's disease and Parkinson's diseases may be also supported by royal jelly, although a detailed animal experiment is necessary.


Quantitative determination of trans-10- Hydroxy-2-Decenoic Acid (10-HDA) in Brazilian royal jelly and commercial products containing royal jelly publication date: Sep 30, 2007
Journal ofApicultural Research Vol. 46 (3) pp. 149-153 DOI 10.3896/IBRA.

Article Title Quantitative determination of trans-10- Hydroxy-2-Decenoic Acid (10-HDA) in Brazilian royal jelly and commercial products containing royal jelly

Author(s) Celira Caparica-Santos and Maria Cristina Marcucci


We report the analysis of Brazilian commercial bee products using high performance liquid chromatography, and a faster method, to detect trans-10-Hydroxy-2-Decenoic Acid or 10-Hydroxy-2-E-decenoic acid (10-HDA) in royal jelly. Determination was carried out using aqueous phosphoric acid 0.1% (pH 2.5)/methanol (50/50) as the mobile phase, and a LiChrospher® RP-18 column with detection at 215 nm. A good linearity was shown between the concentration of 10-HDA and peak area in the concentration range of 5.0-50.0 mg/L (r 0.99, n = 5). The within-day and between-day relative standard deviation (RSD) were1 % and 3 %, respectively.


The six studies that mention 10-Hydroxy-Trans-2-Decenoic Acid:
1.  Inhibition of interferon-γ-induced nitric oxide production by 10-hydroxy-trans-2-decenoic acid through inhibition of interferon regulatory factor-8 induction.
Takahashi K, Sugiyama T, Tokoro S, Neri P, Mori H.
Cell Immunol. 2012;273(1):73-8. Epub 2011 Dec 1.
PMID: 22177846 [PubMed - indexed for MEDLINE]
Related citations

2.Inhibitory effect of 10-hydroxy-trans-2-decenoic acid on LPS-induced IL-6 production via reducing IκB-ζ expression.
Sugiyama T, Takahashi K, Tokoro S, Gotou T, Neri P, Mori H.
Innate Immun. 2012 Jun;18(3):429-37. Epub 2011 Sep 26.
PMID: 21948282[PubMed - in process]
Related citations

3.Antidepressant-like activity of 10-hydroxy-trans-2-decenoic Acid, a unique unsaturated Fatty Acid of royal jelly, in stress-inducible depression-like mouse model.
Ito S, Nitta Y, Fukumitsu H, Soumiya H, Ikeno K, Nakamura T, Furukawa S.
Evid Based Complement Alternat Med. 2012;2012:139140. Epub 2011 Jul 24.
PMID: 21799699 [PubMed]
Free PMC Article
Related citations

4.Estrogenic activities of Fatty acids and a sterol isolated from royal jelly.
Suzuki KM, Isohama Y, Maruyama H, Yamada Y, Narita Y, Ohta S, Araki Y, Miyata T, Mishima S.
Evid Based Complement Alternat Med. 2008 Sep;5(3):295-302.
PMID: 18830443 [PubMed - in process]
Free PMC Article
Related citations

5.Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro.
Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S.Biomed Res. 2007 Oct;28(5):261-6.
PMID: 18000339 [PubMed - indexed for MEDLINE]
Free Article
Related citations

6. [Determination of 10-hydroxy-trans-2-decenoic acid (10-HDA) in royal jelly by gas liquid chromatography].
Ji N, Yu RG, Yang QH, Yu PH, Li Y.
Zhong Yao Tong Bao. 1987 Jul;12(9):28-31, 62. Chinese. No abstract available.
PMID: 3449246 [PubMed - indexed for MEDLINE]
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