Ginkgo: The Hows and Whys for Down Syndrome

Supplementing with Ginkgo Biloba is the first step to getting your child's brain chemistry in order. In experiments with a mouse model with Down syndrome, researchers at Stanford University discovered the main culprit to brain dysfunction in people with DS. They found that the GABA receptors, which regulate inhibition in the brain, are over-active. This means the receptors are ON continuously. As a result, the nerves in the memory and learning area of the brain aren't able to fire correctly. In other words, the nerves are shut down. To compensate for increased activity of the GABA receptor, they successfully used Ginkgo, a GABA antagonist, to turn it down.

Symptoms of GABA overexpression
Compiled by Teresa Cody. I think you'll find these surprisingly familiar!

Organ -- Symptom

Central Nervous system (Brain) -- sleepiness, drowsiness, sedative
Airway Epithelium --  Produces mucous; decreases smooth muscle tone
Stomach -- can cause stomach upset
Small intestine -- control NO-related spontaneous relaxations of the antrum and duodenal circular muscle 
Large intestine -- numerous functions including autocrine, paracrine, excitatory and inhibitory 
Bladder --  inhibitions of urination with increases in bladder capacity
Pancreas -- insulin secretion possibly effected, can inhibit secretion of the blood-glucose-elevating hormore glucagon
Liver -- acts as an inhibitory signal for hepatic cell proliferation
Lungs -- shortness of breath
Skin -- tickling, itchy
Eyes -- eye growth and refractive development 
Retina -- development
Esophagus -- Reflux (acid and nonacid)
Laryngeal motorneurons -- decreases laryngeal moror neurons, inhibits adductor and abductor
Type II Alveolar Epithelium (Lung) -- accelerates fetal lung development, likely through an enhanced cell proliferation and/or fluid secretion.
Muscle -- decreases muscle tone
Sleep -- increase NREM/ Decrease REM       

Lots of details of the effects of ginkgo: http://www.hyperhealth.com/demo/ginkgo_biloba.htm#lnk00000051

Sleep & Ginkgo

In most kids w/DS, ginkgo will help restore their REM sleep, which is important for memory retention. Untreated people with DS show a significant reduction in percentage of REM sleep, a marked delay in first REM latency and a statistically significant decrease in high-frequency rapid eye movements during REM sleep. The percentage of REM sleep in humans can be considered as an index of brain "plasticity" and the high-frequency REMs can represent an index of the brain ability to organize information, which is vital for learning and memory.

The average REM of a typical one year old child is 30%. When Jett is on ginkgo, his REM is at 22.3%, which is remarkable. His doctor said that Jett's sleep study results were the best he had ever seen in a person with DS in his eleven years of experience.

Products

Use only standardized products, as their level of Ginkgolic Acid is reduced to under 5 ppm (parts per million). Non standardized products can cause serious allergic skin reactions due to higher amounts of Ginkgolic Acid content. Look for these two statements show that the product you are using is standardized: "24% Ginkgo flavone glycosides and 6% terpene lactones" or "Ginkgo special extract EGb 761."

Standardized products also guarantee a fixed amount of terpene lactones, including Bilobalide, which is the active component in the therapy for Down Syndrome. If you are using a product that doesn't state one of the two above mentioned things, contact the manufacturer to verify (and share their response with us) or discard it right away.

To make sure you purchase safe ginkgo, consider this:
 
All ginkgo is from China. IMO, China can not be trusted to self-regulate. Therefore, the supplement company has to self-regulate and test the ginkgo for any heavy metals. 

So, not only do we have to look for products with:
 
1) Correct ratio: (most ginkgo meets this criteria)
Flavone glycosides   24%
Terpene lactones   6%
 
2) Must have less than 5 ppm of ginkgolic acid  

BUT ALSO
 
3) The company must spot-test, on a regular basis, random batches of their gingko to make sure it is not tainted with heavy metals. (Ginkgold for sure, does this and Nature's Way as a company, does this. Such testing also needs to be done for fish oils. Source Naturals is good. Rainbow Light is hit or miss.
Metagenics is reliable as well. Companies from Utah seem to be the most reputable and most in California because they have stricter laws. I'm not done researching all of this though.)

It would be great if each of us (you) could email or call your ginkgo company to find out their company's policy and post the answers to save us all a lot of time.

In short, we want to be giving our children SAFE products. At the very least, do no harm...

Brands that fit this criteria:

 

Life Extension Ginkgo http://www.lef.org/Vitamins-Supplements/Item00778/Ginkgo-Biloba-Certified-Extract.html?source=search&key=ginkgo%20biloba

Prothea Brand Ginkgo

Doctor's Best Extra Strength Ginkgo -- 120 mg - 120 Capsules $7.52Doctor's Best Extra Strength Ginkgo -- 120 mg - 360 Vegetarian Capsule $20.24

SW892 Swanson Premium Ginkgo Biloba Extract does list <5 ppm ginkgolic acid on the label.  This product is also standardized to 24% flavone glycosides, and 6% terpene lactones. However, item SWU033 Swanson Ultra Timed-Release Ginkgo does not specifically list the amount of Ginkgolic Acid.  

Link to the brand that they used in the actual study: Nature's Way Ginkgold If you buy the Ginkgold tablets, you'll have to crush the tablet.

I don't recommend the Vitacost brand Ginkgo because they can't verify the level of ginkgolic acid in their product. 

Honeycombs is a trusted brand but the liquid ginkgo is harder to dose because the strength is not equal to the solid form. Teresa Cody does not recommend that you use it. If you do, however, make sure it's alcohol free. Honeycomb has an alcohol free liquid version (that I used with Jett until I found out about the dosage). If your infant is not eating solid foods yet, you may want to use the liquid version.
Ginkgo liquid: http://www.nutrivene.com/view_item.php?id=244
For liquid dosage, you can go here: http://www.riverbendds.org/index.htm
On the left side of the screen, click the folder "Supplements & Drugs" and then the folder "Ginkgo" and then the folder "Dosage."

Time Released Ginkgo that Teresa Cody uses: Natural Sunshine.

Word of caution: if your child is suffering from epilepsy or another seizure disorder, talk with your health care provider first. See side effects below. If you email me, I can get you in contact with several moms whose babies had seizures (unrelated to ginkgo) but are now taking it with no problems.

Dosage Minimum dose is 3.0 mg per pound to see results. (Yes, this has recently increased.) 3mg x 18 lbs = 54 mg. Each capsule is 120 mg. So you'll be giving him 1/2 a capsule in the morning, 1/2 in the afternoon and then 1/2 in the evening. Your goal is to get him taking this 3x a day, about 7 hours apart, with the largest amount before bed. Once he's old enough to swallow pills, you'll move him to the time released tablet that he can take it once in the morning.

This is a conservative introduction. You can modify it as you wish. But wait at least a week before you introduce anything else.

Week 1- give him 1/4 of a capsule (30mg) in the morning. (Always introduce a new thing in the morning so that you can best notice & deal with any side effects.)

Week 2- give him 1/4 of a capsule in the morning & 1/4 of a capsule 7 hours later. (GB has a half life of 7 hours.)

Week 3- give him 1/4 of a capsule in the morning & 1/4 of a capsule before bedtime. (During this period, your child may have a change in sleeping patterns, but it will get back into a normal pattern in a week or so.)

Week 4- 1/4 of a capsule in the morning, 1/4 of a capsule 7 hours later & 1/4 of a capsule 7 hours after that. (That's 90 mg.) If you see that he is easily bruising, then cut back on the amount.

Once you get to week 5, you can increase it as he gains weight.

Jett hasn't experienced any adverse effect of the ginkgo and he's been taking it since at least 4 months of age.


I would love to switch to time release, but Jett can't take tablets yet & grinding would defeat the purpose. So, I'm giving it about every 7 hours. When he awakens early in the am, I give it then because it usually is about 7 hours after I last gave it. It seems to allow him a little more calm sleep for the rest of the morning. (Plus, the less he thrashes, the more I sleep!)

I do give Jett more than the minimum of GB. At 16.8 lbs, he is getting a full capsule a day, 120 mg. I slowly working him up to the full potency of one of my capsules: 120 mg spread throughout the day. Teresa Cody, of CMF, said once you see easy bruising, you have to back down on the dosage.

Explanations of how/why this works:

http://changingmindsaboutdownsyndrome.blogspot.com/2011/03/sleep-part-i.html

http://changingmindsaboutdownsyndrome.blogspot.com/2011/02/can-sleep-be-as-easy-as-gb.html

Research

Here is a great study about the relationship of GABAa (Ginkgo helps restore proper use of GABA) and the production of REM. The full text is available at this link
http://jn.physiology.org/content/92/4/2198.full
The idea that are kids are asleep and not having proper REM state is pretty profound. One needs REM at night to consolidate memory.

GABAA Receptors Inhibit Acetylcholine Release in Cat Pontine Reticular Formation: Implications for REM Sleep Regulation

Jacqueline Vazquez and Helen A. Baghdoyan
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109

Submitted 2 February 2004; accepted in final form 10 June 2004

ABSTRACT

receptor This study used in vivo microdialysis in cat (n = 12) to test the hypothesis that gamma aminobutyric acid A (GABAA) receptors in the pontine reticular formation (PRF) inhibit acetylcholine (ACh) release. Animals were anesthetized with halothane to hold arousal state constant. Six concentrations of the GABAA receptor antagonist bicuculline (0.03, 0.1, 0.3, 1, 3, and 10 mM) were delivered to a dialysis probe in the PRF, and endogenously released ACh was collected simultaneously. Bicuculline caused a concentration dependent increase in ACh release (maximal increase = 345%; EC50 = 1.3 mM; r2 = 0.997). Co-administration of the GABAAagonist muscimol prevented the bicuculline-induced increase in ACh release. In a second series of experiments, the effects of bicuculline (0.1, 0.3, 1, and 3 mM) on ACh release were examined without the use of general anesthesia.
States of wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep were identified polygraphically before and during dialysis delivery of bicuculline. Higher concentrations of bicuculline (1 and 3 mM) significantly increased ACh release during wakefulness (36%), completely suppressed non-REM sleep, and increased ACh release during REM sleep (143%). The finding that ACh release in the PRF is modulated by GABAA receptors is consistent with the interpretation that inhibition of GABAergic transmission in the PRF contributes to the generation of REM sleep, in part, by increasing pontine ACh release.

Possible Side Effects

From Drugs.com:
"There have been published case reports of generalized convulsions and vomiting within several hours after ingestion of large amounts of ginkgo nuts/seeds, including in young children and healthy individuals with no known personal or family history of epilepsy. Many more cases, including fatalities, occurred in Japan in the 1930s to the 1960s during a food shortage when ginkgo nuts served as an important source of food. Some investigators have suggested that the amounts of ginkgotoxin in commercial extracts are too low to exert a detrimental effect. Nevertheless, a case report describes two elderly, previously well controlled epileptic patients who presented with recurrent seizures within two weeks of initiating treatment with a ginkgo extract. Both patients remained seizure-free several months after discontinuing the extract, with no alteration to their anticonvulsant medications."

http://www.drugs.com/drug-interactions/ginkgo-biloba-with-prozac-1115-648-1174-10621.html

The active ingredients in Ginkgo biloba extract account for its antioxidant properties and its ability to inhibit platelet aggregation. Consequently, this herbal product is promoted for use in improving cognitive function and blood flow. To date, however, at least four reports of spontaneous bleeding in association with use of Ginkgo biloba have been published.

One report described a 70-year-old man who presented with bleeding from the iris into the anterior chamber of the eye one week after beginning a self-prescribed regimen consisting of a Ginkgo biloba concentrated extract (Ginkoba), in a dosage of 40 mg twice daily. His medical history included coronary artery bypass surgery performed three years previously. His only medication was aspirin, in a dosage of 325 mg per day, which he had taken since his bypass surgery. After the spontaneous bleeding episode, he continued to take aspirin but discontinued the ginkgo product. Over a three-month follow-up period, he had no further bleeding episodes. Interaction of the ginkgo product and aspirin was considered the cause of his ocular hemorrhage.

Drug interactions

(Aspirin, warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix), dipyridamolePersantine)

Ginkgo biloba may also interact with warfarin (Coumadin). A 78-year-old woman who had been taking warfarin for five years after coronary bypass surgery suffered a left parietal hemorrhage after using a ginkgo product for two months.5 No change was noted in her prothrombin time. The intracerebral bleeding was attributed to the antiplatelet effects of ginkgo.

In another reported case,6 a 33-year-old woman was diagnosed with bilateral subduralhematomas after almost two years of ingesting Ginkgo biloba, in a dosage of 60 mg twice daily. Her other medications were acetaminophen and an ergotamine-caffeine preparation, which she used briefly. While she was taking Ginkgo biloba, her bleeding times were 15 and 9.5 minutes. Within 35 days after she stopped taking the ginkgo product, her bleeding times were normal (three to nine minutes).

An additional case of spontaneous intracerebral hemorrhage was reported in a 72-year-old woman who had been taking Ginkgo biloba, in a dosage of 50 mg three times daily, for approximately six months.7 No history of head trauma could be elicited.

Until further information is available, patients who are taking garlic, vitamin E,8 warfarin, aspirin or other drugs with antiplatelet or anticoagulant effects should be cautioned about potential interactions with ginkgo products. Patients who are taking ginkgo products should be counseled to inform their physician about unusual bleeding or bruising, new-onset headaches or vision changes.

------

Jett is on the complete protocol plus heart meds (Digoxin & Enalapril) and suffers no side effects. His recent CBC shows his platelet count is a little low. My pediatrician is not concerned, but agrees that I should be watching carefully for any bruising, which I haven't seen.

------
First, ginkgo has been used for over 5000 years.

Second, ingestion of too many Ginkgo seeds has been known to cause seizures. The ginkgo we, in the US use, is not in that form. The reports of seizures have are from Japan, because they consider the Ginkgo seed a delicacy. The methylpyridoxine has been cleaned out of the extracts sold in the US.

Third, herbs are highly regulated. A high quality Ginkgo product such as Ginkgold, or Nature's Way products would be the smartest route.

Fourth, to be on the safe side, patients treated with agents that can lower the seizure threshold should preferably avoid the use of products containing ginkgo biloba.

From Drugs.com:
"There have been published case reports of generalized convulsions and vomiting within several hours after ingestion of large amounts of ginkgo nuts/seeds, including in young children and healthy individuals with no known personal or family history of epilepsy. Many more cases, including fatalities, occurred in Japan in the 1930s to the 1960s during a food shortage when ginkgo nuts served as an important source of food. Some investigators have suggested that the amounts of ginkgotoxin in commercial extracts are too low to exert a detrimental effect. Nevertheless, a case report describes two elderly, previously well controlled epileptic patients who presented with recurrent seizures within two weeks of initiating treatment with a ginkgo extract. Both patients remained seizure-free several months after discontinuing the extract, with no alteration to their anticonvulsant medications."

http://www.drugs.com/drug-interactions/ginkgo-biloba-with-prozac-1115-648-1174-10621.html
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Ginkgo page on the Einstein Syndrome Website

Sources http://www.umm.edu/altmed/articles/dementia-000046.htm

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