Don't miss out! Be sure to attend the Down Syndrome Track at the prestigious AutismOne Conference Wednesday, May 22 – Sunday, May 26 at the Intercontinental Hotel O'Hare Chicago in Rosemeont IL. Register Today!
Want free registration? Help us man the DS OPTIONs booth!
The entire Speaker Schedule for AutismOne is available online, but here's the schedule for the Down Syndrome Track:
Wednesday May 22, 2013
9:00 am - 10:00 am
Action Plan for Parents of Children with Down Syndrome
Andi Durkin
10:30 am - 12:30 pm
GAPS™ - Gut And Psychology/Physiology Syndrome
Kristin Gustafson
1:30 pm - 2:30 pm
The Biochemistry of Down Syndrome: Opportunities for Intervention
Kent MacLeod
3:00 pm - 3:55 pm
Let's Learn - Reading Math and Fun Stuff
Alison Wimmer
4:00 pm - 5:00 pm
Glutamate: How to monitor and mediate its effects in Down Syndrome
Erica Peirson, ND
5:00 pm - 6:00 pm
Balance tips for a busy household & Lydia presents her life
Jane Winans
Lydia Winans
Thursday May 23, 2013
9:00 am - 10:00 am
Biomedical and Thyroid Basics: Where to Begin
Norm Schwartz, MD
10:30 am - 11:20 am
Feeding Options and Oral Motor Methods: Paving the Way for Optimal Speech
Jill Rabin M.S. CCC-SLP/L IBCLC
11:30 am - 12:30 pm
Predictive Biomarkers in T21
Russell Jaffe, MD, PhD, CCN
1:30 pm - 2:30 pm
Down Syndrome: Evidence of a Susceptible Subgroup for Vaccine Injury
Laurette Janak
3:00 pm - 3:55 pm
Health Risks for Down Syndrome Moms and What to Do About It
Laurette Janak
4:00 pm - 4:55 pm
Boost Cognition Potential
Anju Usman, MD
5:00 pm - 6:00 pm
Neuroepigenetic Regulation and Down Syndrome
Richard Deth, PhD
7:00 pm - 7:50 pm
Enzymes and Gut Health
Devin Houston, PhD
Hope to see you there!
Please enjoy this collection of notes, research and information to help you best care for your loved one who has a little "extra"! Questions and comments are welcome.
Friday, May 3, 2013
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
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 Albaherbal.com: Royal jelly mental clarity at any age
Products
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.
10-Hydroxy-Trans-2-Decenoic Acid isolated from royal jelly for sale: $114
Says for research purposes only
http://www.scbt.com/datasheet-296572.html
Dosage
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.
Free full text here.
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Full text here
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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.
Abstract
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
University
5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
Summary
Patients suffered 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.1.46.3.05
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
Abstract
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:
Sources
http://weeksmd.com/2009/02/royal-jelly-and-neural-regeneration/
http://www.albaherbal.com/herbal-research/royal-jelly-mental-clarity-at-any-age/
Related Posts
Gingko: The Hows and Whys for Down Syndrome
Longvida Curcumin
Jett's Complete Supplement List
Vitamin C Plays Important Role in Brain Function
Ashwagandha: Good for Brain
Roobios Tea Protects Brain Against CNS Damage
Noggin and BDNF Promotes Neurogenesis
Phosphatidylserine
Ginseng: Benefits to the Brain
Wild Blueberry Extract
EGCG Green Tea Extract For Memory
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
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 Albaherbal.com: 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.
References
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): 800Blum, M.S., Novak A.F. and Taber III, 5. (1959). 10-Hydroxy-decenoic acid, an antibiotic found in royal jelly. Science, 130 : 452-453
Products
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.
10-Hydroxy-Trans-2-Decenoic Acid isolated from royal jelly for sale: $114
Says for research purposes only
http://www.scbt.com/datasheet-296572.html
Dosage
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.
Source
Laboratory of Molecular Biology, Gifu Pharmaceutical University.Abstract
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.
Source
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu 502-8585, Japan.Abstract
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.
Source
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan.Abstract
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.
Abstract
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
University
5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
Summary
Patients suffered 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.1.46.3.05
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
Abstract
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]
Related citations
Sources
http://weeksmd.com/2009/02/royal-jelly-and-neural-regeneration/
http://www.albaherbal.com/herbal-research/royal-jelly-mental-clarity-at-any-age/
Related Posts
Gingko: The Hows and Whys for Down Syndrome
Longvida Curcumin
Jett's Complete Supplement List
Vitamin C Plays Important Role in Brain Function
Ashwagandha: Good for Brain
Roobios Tea Protects Brain Against CNS Damage
Noggin and BDNF Promotes Neurogenesis
Phosphatidylserine
Ginseng: Benefits to the Brain
Wild Blueberry Extract
EGCG Green Tea Extract For Memory
Monday, March 25, 2013
Cerebral folate deficiency in Down syndrome
What is Cerebral folate deficiency (CFD)?
CFD occurs when the amount of the active form of folate in the brain is less than the amount that is in the rest of the body. CFD could be from either a broken process of the folate transport system or from increased folate turnover within the central nervous system. (Cerebral folate deficiency. Ramaekers VT, Blau N.) Symptoms from lack of folates in the brain appear at around four to six months of age.
What are the symptoms?
Source: http://virtualmdpractice.com/CerebralFolateDeficiency.html
If you see these symptoms in your child, bring this information to your child's physician. There are tests that can be done to check for CFD.
What is the Treatment?
And what kind of folate is best for those with the MTHFR variation?
What about folate for those with DS?
Mom and high school science teacher, Linley, pointed out that, in Down syndrome, studies have shown that large doses of calcium folinate produced significant improvement in young ones with DS -- and some of those in the study surely had the MTHFR variation since it's common among those with DS. So it is possible that the l-5MTHF type of folate that works so well in the typical population, especially for those with the MTHFR variation, may not work as well in the DS population since it may skip a step in the process that our kids may need to get folate to the brain.
[But, I haven't seen a study that used L5-MTHF for our kids….]
And folate for those with DS and the MTHFR variation?
Jett has two of the MTHFR variations and also has DS… So, my best educated guess has me giving Jett this:
Here's the more technical reasoning behind this, as written by Linley:
I was giving him 400 mcg for the longest time, then I went up to 2,500 mcg divided by two doses (am and afternoon) to see if I could see a real difference. I did! I stayed there for 3 days with no ill effects. Then I went up to 5,000 mcg to see what would happen, divided into two doses. Still nothing bad for 3 days. Yesterday, I gave him 7 tablets in the am and 6 tablets in the afternoon. Each time I gave him one of the meth folate just in case. But he had no problems w/the methyl. This morning, he woke up reciting the days of the week (I don't think it was in order, though). He said them all then said, "Days of the week!" He said, "Today is Saturday!" (There's no way he could know it's Saturday... I think he was repeating a sentence he had learned and just happened to get the day right.) Most importantly, I didn't teach him this! But, yesterday morning, he read the "Monday's child fair of face..." poem and he may have seen a short video on Youtube with the days of the week song. But I didn't teach him this because I figured he's too young to understand what it is. It really freaked my husband and I out this morning!! This is the most and quickest he's learned anything. But, I've been giving him the Royal Jelly for two days as well now.... Crazy! We are going to try to do a video of him soon. Because it's pretty unbelievable. I'm thinking of recording him reading a welcome message on my blog.
My Results
About five months after starting...
Because the large amount of folate may have causes Jett to skip his afternoon nap on occasion, I decreased the dose to 2,400 mcg in the morning and 1,600 mcg in the early afternoon. This dose seems to be working for him because: At almost 3 years old, Jett's head is finally in proportion to his body! Yeah! His height, weight and head size are all that of a typical 17 month old. (Okay, so I'm working on this.) This change to perfect proportion -- the first time since before I started monitoring at 12 months -- could be due to finally taking the proper folate, at the right dose.
Usually he gets both kinds of folate, but sometimes he just gets one or the other at the same dose, not on purpose, but because of running out of this or that.
He continues to progress. At 3 years old, he says many multi-word sentences a day, mixed in with one word "demands" and his coordination is improving with better, more confident walking, etc. Yesterday, we had to stop on our way home because he had to use the potty and when we walked into the bathroom he said, "What a mess! Toilet paper is everywhere!" I've used other therapies and added more supplements since increasing his folate. But it's just a note that he is not stalling, but continuing to progress.
Liquid versions:
Designs for health super liquid folate and this one has BOTH good types of folinic/folate AND B12: Methyl Protect by Biogenesis Nutraceuticals
Research/Sources for more information
Narumi Y, Shiihara T, Yoshihashi H, Sakazume S, van der Knaap MS, Nishimura-Tadaki A, Matsumoto N, Fukushima Y. Hypomyelination with atrophy of the basal ganglia and cerebellum in an infant with Down syndrome. Clinical Dysmorphology. 2011;20:166-167. Available at: http:/
Title of Research: Down Syndrome Disintegrative Disorder: Possible Hashimoto’s Encephalopathy?
Summary of Proposed Project:
Lay Summary of Proposed Project:
A Milk-Free Diet Down Regulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome, as printed on NIH Public Access, July 2009
Excerpt:
Read the full story here.
Dev Med Child Neurol. 2004 Dec;46(12):843-51.
CFD occurs when the amount of the active form of folate in the brain is less than the amount that is in the rest of the body. CFD could be from either a broken process of the folate transport system or from increased folate turnover within the central nervous system. (Cerebral folate deficiency. Ramaekers VT, Blau N.) Symptoms from lack of folates in the brain appear at around four to six months of age.
What are the symptoms?
Source: http://virtualmdpractice.com/CerebralFolateDeficiency.html
- delayed development
- deceleration of head growth
- low muscle tone (hypotonia)
- muscular coordination failure; irregularity of muscular action (ataxia)
- dyskinesias- a condition marked by abnormal movements of the body that have a combined choreic [ceaseless occurrence of rapid, jerky, involuntary movements] and athetoid pattern [uncontrolled rhythmic writhing movement, esp of fingers, hands, head and tongue]
- hemiballismus- a very rare movement disorder with involuntary flinging motions of the extremities -- often violent and involving one side of the body
- spasticity- stiff or rigid muscles. It may also be called unusual "tightness" or increased muscle tone.
- speech difficulties
- epilepsy
If you see these symptoms in your child, bring this information to your child's physician. There are tests that can be done to check for CFD.
What is the Treatment?
A milk-free diet and oral treatment with the correct kind of folate: 5-formyltetrahydrofolate (5MTHF), may be started in low doses at 0.5-1mg/kg/day, but in some patients higher daily doses of folinic acid at 2-3 mg/kg/day are required to normalize the CSF 5MTHF values. Source: http://cfdresearch.org/Links.html and https://sites.google.com/site/superdownsyndrome/thyroid/hashimotos
According to the study on children with DS (see below), the therapeutic dose is 1 mg of calcium folinate per kg. When I started, Jett weighed over 10 kg, so he needed up to 10 mgs or 10,614 mcgs of folinic acid, that's 13 tablets at 800 mcg each. See my notes below for how I proceeded and my results.
The DS diagnosis, however, complicates the folate issue... Read on:
What kind of folate is best for the typical population?
At present, two types of folates that occur naturally in foods are
available as over-the-counter supplements. One is folinic acid, usually
sold over-the-counter as “calcium folinate.” Calcium folinate is also
available by prescription as Leucovorin®, which, unfortunately, is
considerably more expensive and also contains FD&C yellow #10 and
FD&C blue # 1, neither of which improves clinical results. (From http://tahomaclinicblog.com/
The other over-the-counter naturally occurring folate presently available is 5-methyltetrahydrofolate (5-MTHF). It’s more expensive than over-the-counter calcium folinate, but more likely to be effective for individuals with “hidden” genetic defects in folate metabolism. [He's referring to the MTHFR variation.] (From http://tahomaclinicblog.com/folic-acid/)
What about folate for those with DS?
Mom and high school science teacher, Linley, pointed out that, in Down syndrome, studies have shown that large doses of calcium folinate produced significant improvement in young ones with DS -- and some of those in the study surely had the MTHFR variation since it's common among those with DS. So it is possible that the l-5MTHF type of folate that works so well in the typical population, especially for those with the MTHFR variation, may not work as well in the DS population since it may skip a step in the process that our kids may need to get folate to the brain.
[But, I haven't seen a study that used L5-MTHF for our kids….]
And folate for those with DS and the MTHFR variation?
Jett has two of the MTHFR variations and also has DS… So, my best educated guess has me giving Jett this:
1 mg of calcium folinate per 1 kg,
but, since Jett has two copies of the MTHFR variation, I substitute one tablet of the l-5MTHF type of folate just to make
sure he has that as well in case he needs it. So, he gets 6 tablets of
the calicium folate and 1 tablet of l-5MTHF in the morning and then 5
tablets of the calicium folate and 1 tablet of l-5MTHF in the afternoon (at 800 mcg each).
I came to this dose from reading the studies below. For a baby under 18 months, they capped the dose at 5 mg, regardless of weight. For those above 18 months, the dose is capped at 15 mg. After 6 months of treatment, the dosage needs to be readdressed. After 6 months, Jett is down to 3 tablets in the morning and 2 in the afternoon (at 800 mcg each), still a mix of l-5MTHF and calcium folinate.Here's the more technical reasoning behind this, as written by Linley:
#1) folinic acid doesn't require DHFR to be
converted. So it bypasses DHFR in a sense. #2) by a alternate route,
folinic acid is converted into THF. This is where the bottleneck is
happening with 5-MTHF, because of the low methionine synthase. so
hopefully, with folinic providing THF, then that portion of the cycle
can at least move forward, or some usable form of folate is being
provided to the cycle.
Here is another compounding factor however, that I recently encountered. It has been suggested in research that if there is mitochondrial dysfunction, particularly with Complex 1 of the electron transport chain, then there isn't even enough ATP being produced to provide energy for folate (either 5-MTHF or folinic) to even cross into/be up taken into the central nervous system. This being the case, it seems a moot point which form of folate to use until mitochondrial dysfunction is addressed.
Hmmm… we'll have to address the mitochondrial dysfunction dilemma in a different post… Here's Life Extension's answer for the typical population. (You'll notice that some of the suggestions are already explored on my blog and that Jett is taking some of the steps they recommend.) Here is another compounding factor however, that I recently encountered. It has been suggested in research that if there is mitochondrial dysfunction, particularly with Complex 1 of the electron transport chain, then there isn't even enough ATP being produced to provide energy for folate (either 5-MTHF or folinic) to even cross into/be up taken into the central nervous system. This being the case, it seems a moot point which form of folate to use until mitochondrial dysfunction is addressed.
My notes about Jett and folate
At 2.6 years old, Jett has an usually small head for his age since his body size is that of a typical 16.2 month old, but his head size is at only 10 months. He has some other symptoms of cerebral folate deficiency that are also usually consistent with a child with DS. I've been searching for a reason for quite some time.
The cure is a milk free diet, which he's already been on since before a year old, and the correct dosage of calicium folinate. I was giving him calicium folinate at 400-800 mcg a day as per the CMF protocol since before a year old, and then, when I found out that he had the MTHFR variation and once I understood what that meant (my ped told me what I was doing with him at the time was fine -- which was incorrect), I started giving the l-5 methyltetrafolate at the same dose.
The proper dose is 1 mg of calcium folinate per kg. And
its the folinic not the meth kind of folate. So I started yesterday with 2,500 mcg to
see what would happen. Huge cognitive leaps! He made up his first, original three-word
sentence. (That I can recall.) I was filing my nails and he looked puzzled then said, "Mommy
scratch stick," matter of factly.
While he's known the parts of his body for a long time, he only would say one or two parts at a time. Yesterday, he said, "eyes, mouth, nose, ears, head and body!" and touched them all. So his expressive language improved immediately! Today he sang the entire Mary Poppins song where the children advertise for a new nanny, with my husband. (He did skip some words, of course -- he's 2.6 years old.)
While he's known the parts of his body for a long time, he only would say one or two parts at a time. Yesterday, he said, "eyes, mouth, nose, ears, head and body!" and touched them all. So his expressive language improved immediately! Today he sang the entire Mary Poppins song where the children advertise for a new nanny, with my husband. (He did skip some words, of course -- he's 2.6 years old.)
A few days later...
I have since increased the folinic to 5,000 mcg a day. He's comprehending books and TV shows better and having more specific verbal requests. Like I wrote on the magnadoodle a short "experience story": "Jett sat in the kitchen playing with a box. Jett found a soft, white, fluffy piece of cotton. Jett played with the cotton." Jett read it to himself and smiled and smiled. Then he pointed to the kitchen, went in, and came back with the piece of cotton and laid it on the magna doodle! (It was a shipment box of vitamins and the cotton from a vitamin bottle.) How many kids at his age have that strong of a reading comprehension?? AND, he learned from context clues what "cotton" was -- I didn't pick up the cotton and say "cotton." He figured out what is was by the adjectives I used when writing about it!
I have since increased the folinic to 5,000 mcg a day. He's comprehending books and TV shows better and having more specific verbal requests. Like I wrote on the magnadoodle a short "experience story": "Jett sat in the kitchen playing with a box. Jett found a soft, white, fluffy piece of cotton. Jett played with the cotton." Jett read it to himself and smiled and smiled. Then he pointed to the kitchen, went in, and came back with the piece of cotton and laid it on the magna doodle! (It was a shipment box of vitamins and the cotton from a vitamin bottle.) How many kids at his age have that strong of a reading comprehension?? AND, he learned from context clues what "cotton" was -- I didn't pick up the cotton and say "cotton." He figured out what is was by the adjectives I used when writing about it!
I was giving him 400 mcg for the longest time, then I went up to 2,500 mcg divided by two doses (am and afternoon) to see if I could see a real difference. I did! I stayed there for 3 days with no ill effects. Then I went up to 5,000 mcg to see what would happen, divided into two doses. Still nothing bad for 3 days. Yesterday, I gave him 7 tablets in the am and 6 tablets in the afternoon. Each time I gave him one of the meth folate just in case. But he had no problems w/the methyl. This morning, he woke up reciting the days of the week (I don't think it was in order, though). He said them all then said, "Days of the week!" He said, "Today is Saturday!" (There's no way he could know it's Saturday... I think he was repeating a sentence he had learned and just happened to get the day right.) Most importantly, I didn't teach him this! But, yesterday morning, he read the "Monday's child fair of face..." poem and he may have seen a short video on Youtube with the days of the week song. But I didn't teach him this because I figured he's too young to understand what it is. It really freaked my husband and I out this morning!! This is the most and quickest he's learned anything. But, I've been giving him the Royal Jelly for two days as well now.... Crazy! We are going to try to do a video of him soon. Because it's pretty unbelievable. I'm thinking of recording him reading a welcome message on my blog.
My Results
About five months after starting...
Because the large amount of folate may have causes Jett to skip his afternoon nap on occasion, I decreased the dose to 2,400 mcg in the morning and 1,600 mcg in the early afternoon. This dose seems to be working for him because: At almost 3 years old, Jett's head is finally in proportion to his body! Yeah! His height, weight and head size are all that of a typical 17 month old. (Okay, so I'm working on this.) This change to perfect proportion -- the first time since before I started monitoring at 12 months -- could be due to finally taking the proper folate, at the right dose.
Usually he gets both kinds of folate, but sometimes he just gets one or the other at the same dose, not on purpose, but because of running out of this or that.
He continues to progress. At 3 years old, he says many multi-word sentences a day, mixed in with one word "demands" and his coordination is improving with better, more confident walking, etc. Yesterday, we had to stop on our way home because he had to use the potty and when we walked into the bathroom he said, "What a mess! Toilet paper is everywhere!" I've used other therapies and added more supplements since increasing his folate. But it's just a note that he is not stalling, but continuing to progress.
Products
(You'll need to give B12 with folate.)
Source Naturals MegaFolinic™ -- 800 mcg - 120 Tablets) is the calcium folinate.
Metagenics FolaPro® -- 60 Tablets is the l-5MTHF type of folate.
Neurobiologix Methyl Folate with Activating Co factors
I haven't tried this yet, but it sounds good. It has both
5-methyltetrahydrofolate and folinic acid as well as niacinamide which helps with the symptoms you may get from using a lot of 5-MTHF. I did get the adverse symptoms when I first took l-5-MTHF and this product would have been nice to have then.
Kirkman's Folinic Acid
B12 spray
(You'll need to give B12 with folate.)
Source Naturals MegaFolinic™ -- 800 mcg - 120 Tablets) is the calcium folinate.
Metagenics FolaPro® -- 60 Tablets is the l-5MTHF type of folate.
Neurobiologix Methyl Folate with Activating Co factors
I haven't tried this yet, but it sounds good. It has both
5-methyltetrahydrofolate and folinic acid as well as niacinamide which helps with the symptoms you may get from using a lot of 5-MTHF. I did get the adverse symptoms when I first took l-5-MTHF and this product would have been nice to have then.
B12 spray
Liquid versions:
Designs for health super liquid folate and this one has BOTH good types of folinic/folate AND B12: Methyl Protect by Biogenesis Nutraceuticals
Research/Sources for more information
Narumi Y, Shiihara T, Yoshihashi H, Sakazume S, van der Knaap MS, Nishimura-Tadaki A, Matsumoto N, Fukushima Y. Hypomyelination with atrophy of the basal ganglia and cerebellum in an infant with Down syndrome. Clinical Dysmorphology. 2011;20:166-167. Available at: http:/
Title of Research: Down Syndrome Disintegrative Disorder: Possible Hashimoto’s Encephalopathy?
Summary of Proposed Project:
The prevalence of autoimmune
disease is much higher in Down Syndrome (DS) than in the general
population. We have encountered 10 patients in the Duke DS Comprehensive
Clinic who developed cognitive regression, autistic characteristics,
and insomnia beginning in their early teenage years. These patients all
had thyroid autoimmunity without clinical thyroid disease. Cognitive and
developmental regression associated with thyroid autoimmunity has not
previously been described in children with DS. We are naming this
condition DS Disintegrative Disorder (DSDD), because of its similarity
to Disintegrative Disorder in three to five year old typical children.
Hashimoto’s Encephalopathy (HE) is an autoimmune CNS disease associated
with but not caused by thyroid autoimmunity, most commonly reported in
adults, but also reported to occur in some children. Cerebral folate
deficiency is caused by either autoimmunity to a tissue folate receptor
or by abnormalities of folic acid metabolism. In children, cerebral
folate deficiency can also lead to autism, regression, and insomnia.
Chromosome 21 contains many genes for folate metabolism, folate
transport, and for enzymes that require folate for activity (including
N6ANTI).
The purpose of the study is to
characterize the clinical and laboratory findings in DSDD; evaluate
thoroughly all patients with DSDD for known metabolic causes of
regression; to test the hypotheses that antibodies to the tissue folate
receptor and to alpha enolase are present in some subjects; and to
evaluate subjects for evidence of abnormal folate metabolism.
Lay Summary of Proposed Project:
The prevalence of autoimmune
disease is much higher in Down syndrome (DS) than in the general
population. It appears that a subset of adolescent patients in the Duke
Comprehensive DS Clinic have experienced significant regression. We
would like to systematically evaluate these patients by review of
medical records, laboratory evaluations, neuropsychological evaluations,
and speech and language testing, and then compare the patients’ data to
draw conclusions about their similarities. We are going to test these
patients to see if they have a problem using folate correctly, and if
they do, our next step in a future study is to treat the patients with
folinic acid to see if their symptoms, such as learning, social
withdrawal, perseverative thoughts, or trouble sleeping improve with
treatment. Describing this subset of patients in the medical literature
will help other clinicians caring for people with DS identify this dual
diagnosis and monitor or treat these patients appropriately.
A Milk-Free Diet Down Regulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome, as printed on NIH Public Access, July 2009
Excerpt:
In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody cross reactivity with milk FR from different species prompted us to test the effect of a milk-free diet.
Read the full story here.
Dev Med Child Neurol. 2004 Dec;46(12):843-51.
Cerebral folate deficiency. Ramaekers VT, Blau N.
Source
University Hospital Aachen, Germany. vramaekers@skynet.beAbstract
Cerebral folate deficiency (CFD) can be defined as any neurological syndrome associated with low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), the active folate metabolite, in the presence of normal folate metabolism outside the nervous system. CFD could result from either disturbed folate transport or from increased folate turnover within the central nervous system (CNS). We report on a novel neurometabolic syndrome in 20 children, which we term 'idiopathic CFD'. Typical features became manifest from the age of 4 months, starting with marked unrest, irritability, and sleep disturbances followed by psychomotor retardation, cerebellar ataxia, spastic paraplegia, and dyskinesia; epilepsy developed in about one third of the children. Most children showed deceleration ofhead growth from the age of 4 to 6 months. Visual disturbances began to develop around the age of 3 years and progressive sensorineural hearing loss started from the age of 6 years. Neuroimaging showed atrophy of frontotemporal regions and periventricular demyelination in seven children, slowly progressive supra- and infratentorial atrophy in three children, and normal findings in the remainder. Because active folate transport to the CNS occurs through receptor-mediated folate receptor protein 1 (FR1) endocytosis, DNA sequencing of the FR1 gene was performed and found to be normal. However, CSF protein analysis revealed a non-functional FR1 protein, suspected to result from either post-translational defects of FR1 protein N-glycosylation, the presence of folate antagonists with irreversible binding, or autoantibodies blocking the folate binding site of FR1. Oral treatment with 5-formyltetrahydrofolate (folinic acid) should be started in low doses at 0.5-1mg/kg/day, but in some patients higher daily doses of folinic acid at 2-3 mg/kg/day are required to normalize CSF 5MTHF values. This proposed treatment protocol resulted in a favourable clinical response in patients identified before the age of six years while partial recovery with poorer outcome was found beyond the age of 6 years. Careful clinical and EEG monitoring should be performed 1, 3, and 6 months after the beginning of treatment. After four to six months of folinic acid treatment, CSF analysis should be repeated in order to prevent over- or under-dosage of folinic acid. Secondary forms of CFD have been recognized during chronic use of antifolate and anticonvulsant drugs and in various known conditions such as Rett syndrome, Aicardi-Goutières syndrome, 3-phosphoglycerate dehydrogenase deficiency, dihydropteridine reductase deficiency, aromatic amino acid decarboxylase deficiency, and Kearns-Sayre syndrome. The pathogenic link between these underlying specific disease entities and the observed secondary CFD has not been resolved.
- PMID:
- 15581159
- [PubMed - indexed for MEDLINE]
LinkOut - more resources
Related Posts
Why B12 & Folinic Acid for Down syndrome?
How to Prevent DS in Your Next Child in 60% of Moms
Tests and Treatment for Mom
Folic Acid Cut Alzheimer’s Risk in Half
Saturday, March 23, 2013
Prenatal Supplementation
 |
| 3 year old Jett and Mommy's growing tummy |
Which prenatal multivitamin is best?
The prenatal vitamins for the typical population won't work as well for you. There are only a few prenatals that we have to choose from.
Ones to consider:
NuTriVene's Prenatal Formula
This multivitamin is specially formulated for us, contains folic acid which 45% of the typical population should not take and 60% of our population shouldn't take. If you are sure that you do not have the MTHFR variation, then it would be a fine product to take. For more information on MTHFR and how it relates to having a child with DS, go to the How to Prevent DS in Your Next Child in 60% of Moms post. Has iron, though (see below).
Thorne Research Basic Prenatal
It's a trustworthy brand, since it does regular batch testing to make sure low heavy metals, and has the correct folate, but it has iron in it, which we don't need since our children are sensitive to metals such as iron. Iron can also cause constipation and too much iron can cause problems in our children. See Anemia Causes & Cures for an explanation as to why iron is an issue. If low iron is an issue, take a look at the above posts. I was able to get Jett's iron levels up just with taking extra Vitamin C since it helps the body process iron better. (See the Vitamin C Plays Important Role in Brain Function post for details on how this works and what to take.)
Emerald Labs Prenatal
ELP has the correct folate, but it has the wrong kind of vitamin C (no big deal) more importantly, it has spirulina in it which is great for the typical population, but our kids need to avoid it because of increased SOD. (See Increased superoxide dismutase and Down's syndrome for details.) It also has iron... see note above.
The Vitamin Code Raw Prenatal
This brand has naturally occurring folate but you would need to supplement with Folapro (l-5-methyltetrahydrofolate). It's gluten free and has no spirulina, although it does have raw spinach (also to be avoided since it's a goitrogen and may interfere with thyroid function. See Raw Spinach and the Thyroid). I did take it for a couple of years while breastfeeding Jett. It also has iron.
Seeking Health Optimal Multivitamin
This is the multivitamin I'm presently taking. It's not actually a prenatal vitamin, but everything is great in it--it has high quality choice types of vitamins, minerals and enzymes. It does have a little bit of spirulina in it. It includes EGCG -- which is great for our kids, but can interfere w/folate absorption. I take both kinds of good folate to combat this possibility. However, new research from Tufts Medical Center show benefits to the baby when Moms do take EGCG during pregnancy! Email me and I'll send you the study.
Neevo DHA
You'll need a prescription for this prenatal vitamin that has the correct folate. Good for those with insurance since it will probably be covered. For more information, check out this article at voices.yahoo.com. However, it does contain synthetic dyes with propylene glycol and soy... items you might want to avoid... Read the package insert with the ingredient list.Additional Supplementation
In addition to supporting overall health, our treatment goals are to address the problems particular to our situation.
We need to:
- lower homocysteine and increase methylation (See Maternal homocysteine level and markers used in first-trimester screening for fetal Down syndrome.)
- address the MTHFR variation (see study on MTHFR and Down syndrome pregnancy)
- support brain growth and formation
- reduce oxidative stress (since our kids experience this even in the womb! See Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid)
L-methylfolate 1 mg (check out how much to take and side effects)
Methylcobalamin 2 mg (B12) sublingually or through a shot
Betaine or trimethylglycine (TMG)
Vitamin B6 as P5P
Magnesium
The MTHFR Prenatal vitamin protocol
For those of you with the MTHFR variation, you may want to consider this list:
a good prenatal (one of the above)
additional 1mg 5-L-MTHF 2x/day (see folate recommendations below)
baby aspirin 1x/day
omega 3s 2x/day
B12 1x/day
Vitamin D (5-10,000 iu 1x/day) (controversially large dose)
Learn more at mthfr.net or speak with a doctor who understands the variation.
Folate recommendations
In addition to the prenatals above, extra folate is needed. The best type is the active form of folate called L-5-methyl tetrahydrofolate as Metafolin. Unlike folic acid, this active form of folate requires no additional metabolic steps for the body to use it, making it a preferred choice for many moms. Folate is an essential nutrient for many body processes, including hormone metabolism, DNA synthesis, homocysteine metabolism, and nervous system function. Be sure to check out these articles on how much to take and side effects.
Support Brain Growth and Formation
Choline
DHA
Vitamin C
Tveden-Nyborg P, Vogt L, Schjoldager JG, Jeannet N, Hasselholt S, Paidi MD, Christen S, Lykkesfeldt J.
Maternal Vitamin C Deficiency during Pregnancy Persistently Impairs Hippocampal Neurogenesis in Offspring of Guinea Pigs. PMID: 23119033
Gotu Kola
(not commonly given in relation to one of our pregnancies--I took it during my pregnancy with Jett to prevent varicose veins and only later found out about the great benefits to the brain. Jett has been taking it for a month with great results [better mood, increased sociability, increased sentence length] and I have just started taking it during this pregnancy. I am working on a post about this. I can send you my unfinished post if you'd like -- just FB or email me.)
Antioxidants
Pick your favorite that is okay to take while pregnant. I've chosen ubiquinol.
Products I use
Vitacost's B12
(I will be buying a different B12 next time, see: for the other forms that are acceptable.)
Folate
Source Naturals MegaFolinic™ -- 800 mcg - 120 Tablets $8.07
and Metagenics FolaPro® -- 60 Tablets $19
other suggestions (or ones that I've bought as well)
Thorne Research 5-Methyl-tetrahydrofolate
Jarrows Methyl Folate
Life Extension Optimized Folate
These are the best over the counter choices, but see if your doctor will prescribe Deplin (l-methylfolate) or Metanx at your next appointment so your insurance can cover it.
Jarrow brand TMG
Vitacost brand B6
YS Eco Farms bee pollen for a range of B vitamins (make sure you're not allergic first).
LifeExtension Neur-Mag (magnesium L-threonate)
Also look into iodine supplementation to support proper hormone function.
For DHA/EPA/fish oil, etc. I trust green pastures the most.
Nordic Naturals DHA
Ubiquinol (Coenzyme Q10)
If you are a vegetarian…
Unfortunately, lack of B12… often found in meat, is a key nutrient that you need a lot of… So, take the most bioavailable forms of B12 and try to eat foods high in B12. Some safe foods for those during pregnancy would be the smaller fish (less toxins) like herring (312% DV) and sardines (149%). Eggs are a great source, for choline as well. (Barely cooked yolks w/fully cooked whites from organic pasture raised chickens is what we eat.) And cheeses such as Swiss cheese provide 3.34μg (56% DV) per 100g serving, followed by Gjetost (40% DV), Mozzarella(39% DV), Parmesan (38% DV) and Tilsit (35% DV).
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