Tuesday, September 27, 2011

Why B12 & Folinic Acid for Down syndrome?

Studies suggest that an inadequate amount of vitamin B12 may be a risk factor for brain atrophy (shrinking) and possible cognitive impairment. Studies also show that individuals with Down syndrome commonly have low levels of B12 and Folic/Folinic Acid (or folate). In one study, typical seniors who took B12 supplements did a better job of holding cognitive declines at bay than placebo. Since the brain of a person with DS has similar qualities of a brain of an elderly person, we need to pay attention to studies about seniors. Supplementing with B12 and Folinic Acid also helps to normalize metabolism. 

Folic/Folinic Acid (or folate) is particularly important within our population since it is needed for the synthesis of DNA and RNA, which are the building blocks of cells. They also help prevent changes to the DNA that could lead to cancer such as leukemia, which our population is particularly susceptible to. It is also needed in both children and adults to be able to make normal red blood cells and prevent anemia. Specifically, B12 and Folinic Acid are used in a metabolic cycle called the SAM cycle.
Please visit Changing Minds Foundation's page on B12 and Down syndrome for more details.

Dr. Oz recently did a great show on B12, not specific to T21, but a nice overview: http://www.doctoroz.com/episode/americas-b12-deficiency 

Types of Folic Acid, Folinic Acid and Folates

Folic acid, actually, should be avoided in the DS population, those with the MTHFR variation (much more common in the DS and autism population and in mothers of children with DS) and older moms who want to have children. See   How to Prevent DS in Your Next Child in 60% of Moms for details as to why folic acid is difficult to process and properly use in our bodies. For this population, folic acid should be avoided in enriched foods such as breads and cereal as well.

Folinic acid also known as Calcium Folinate has been shown to have positive effects on children with DS whether or not they have the MTHFR variation.

Folate is a broad term, it may refer to Calcium Folinate, "naturally occuring folate" which may be folinic acid or could be a form of l-5-methylfolate. If it's not clear on the label, I'd contact the company to make sure of the source. 

Calcium Folinate has been shown to have positive effects on children with DS whether or not they have the MTHFR variation. It's not recommended for the typical population who has the MTHFR variation.

L-5-MTHFR, l-5-methyltetrahydrofolate, 5-methylfolate, etc. is the folate of choice for those with the MTHFR variation. (This is what I take. Jett has both DS and MTHFR so I give him both, just in case. Hopefully I'll eventually learn which is best but I'm covering my bases.)

For more info on types, see Cerebral folate deficiency in Down syndrome 


Birth to 2 years: 200-400mcg
Children 2- 12 years old: 400-1000mcg
Teen/Adults: 1000-2000mcg

Folinic Acid
Birth to 2 years: 200 mcg
Children 2- 12 years old: 400-800 mcg
Teen/Adults: 800-2000 mcg
For products, see the DS Day to Day Store

Different children need different forms of B12. If your child has one or more of the MTHRF mutation, the methylcobalamin is preferable (40% of the typical population has this mutation. Jett does). With some kids, if you give the full dose the first day, it causes hyperactivity. If you see this happening, reduce the dose and slowly increase each day until you reach the full dose. If problems still occur with methylcobalamin, look into the hydoxocobalamin form (see healthy awareness article below).

B12 can be difficult to metabolize so you don't want to give it in food or have them shallow it. Instead, buy sublingual drops or mouth or nose spray or other easy to assimilate form. It also needs to be taken on an empty stomach, 
first thing in the morning works well. If your child still has low levels of B12, you can look into the B12 shots (watch out for extra ingredients in the shot, however).

Methylcobalamin B12 

B12 drops
This is what I use for myself. I just put the drops under my tongue first thing in the morning and try not to swallow, rather allow it to dissolve in my mouth.

B12 spray
This is what I use for Jett first thing in the morning. It sprays a fine film all over his mouth so that it's more likely to be absorbed in his mouth rather than to go down his throat.

More B12 Liquid versions

Designs for health super liquid folate

This one has BOTH good types of folinic/folate AND B12: Methyl Protect by Biogenesis Nutraceuticals

My stepson, with ASD, uses the sublingual lozenge that he sucks on while getting ready for school in the mornings. (I don't necessarily trust that he won't swallow the liquid and spray.)

Hydoxocobalamin B12
(The brand ProHealth has sorbitol in its tablets so I haven't included them in this list.)

sublingual drops $40
Revelation Health Hydroxo-B12
(I've sent them an email for their list of ingredients to see if this product can stay on this list.)

Sublingual spray $60 for 3 month supply
Blue Rock Holistics Hydroxade
(I've sent them an email for their list of ingredients to see if this product can stay on this list.)

Here's a great page that gives more information about the different forms of B12: http://www.healthyawareness.com/articles/about-vitamins-minerals/about-vitamin-b12.aspx

Calcium folinate

Source Naturals MegaFolinic™ -- 800 mcg - 120 Tablets

Kirkman's Folinic Acid


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.

Seeking Health's l-5-mthf


Brain Takes Multiple Hits from Low B12 Levels
By Crystal Phend, Senior Staff Writer, MedPage Today

Published: September 26, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Low levels of vitamin B12 may contribute to cognitive problems for older adults in more than one way, according to a cross-sectional study…. 
...Note that previous studies have suggested that poor vitamin B12 status may be a risk factor for brain atrophy and possibly cognitive impairment.
Note that in this study, concentrations of vitamin B12–related markers (methylmalonate, cystathionine, homocysteine) were associated with global cognitive function and with total brain volume…. 
...Although her group's observational study couldn't say whether boosting B12 would prevent or reverse cognitive effects, a prior randomized trial demonstrated that high-dose B complex supplements could slow down brain atrophy in older adults.
In that study, dubbed VITACOG, supplements did a better job of holding cognitive declines at bay than placebo among those with high homocysteine levels.
"So at least from this one clinical trial it appears that [supplementation] may have some benefit," Morris argued.
Her group dug deeper into their Chicago Health and Aging Project (CHAP), measuring vitamin B12-related markers in relation to brain MRI and neuropsychological test results 4.6 years later in 121 residents of Chicago's South Side, ages 65 and older.
After adjustment for age, sex, education, race, and serum creatinine levels to control for renal function problems that could have an impact on homocysteine, all of the B12-related markers affected global cognitive scores….

..."You might be in the normal range, say in the low normal range, of vitamin B12 in your blood but still have evidence of insufficient vitamin B12 based on these biomarkers," she told MedPage Today….
Primary source: NeurologySource reference:Tangney CC, et al "Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination" Neurology 2011; 77: 1276–1282.

Low Vitamin B12 Tied to Brain Atrophy, Cognitive Impairment


Total blood mercury and serum measles antibodies in US children, NHANES
Gallagher CM, Smith DM, Meliker JR.
Sci Total Environ. 2011 Dec 1;410-411:65-71. Epub 2011 Oct 10.

Background: Environmental toxins, pathogens and host susceptibility cofactors may interact to contribute to disease. In vitro mercury exposure inhibited antiviral cytokines in human cells; however, little is known about the relationship between mercury and viruses in children. Children are susceptible to mercury toxicity; lower vitamin B-12 and folate levels and higher homocysteine levels may represent susceptibility cofactors.
This study aimed to evaluate associations between total blood mercury (Hg) and measles antibodies in children, and the influence of these susceptibility cofactors.

Design: Cross-sectional data on serum measles antibodies, Hg, homocysteine, methylmalonic acid (MMA, indicator of B-12 deficiency), and folate were obtained from the 2003--2004 NHANES for children aged 6--11 years with measles seropositivity (n=692). We used linear regression to evaluate relationships between measles antibodies and Hg, stratified by sex, MMA ?, folate b, and homocysteine?sample medians, adjusted for demographic, nutritional and environmental cofactors.

Results: Hg (range: 0.10--19.10 ?g/L) was inversely associated with measles antibodies (range: 1.00--28.24 units) in non-stratified analysis (n=692), yet positively associated among the subset of boys with higher MMA and lower folate (n=98). Among this subset with higher homocysteine levels (n=61), correlations were positive across all Hg quartiles relative to Q1 (Hg?0.20 ?g/L): Q2:?=6.60 (3.02, 10.19); Q3:?=8.49 (6.17, 10.81);
Q4 (HgN0.80 ?g/L):?=4.90 (2.12, 7.67) (ptrend=0.077).

Conclusion: Stratification by susceptibility cofactors revealed opposing directionality for correlations between Hg and measles antibodies, with positive effect estimates at lowest exposures only among boys with higher MMA, lower folate and higher homocysteine levels.

Related Posts

Folic Acid Cut Alzheimer's Risk by Half

Alzheimer's Disease & Down syndrome

Jett's Supplement List

Thyroid Issues & DS Go Hand in Hand

Which Multivitamin?

Anemia Causes & Cures

Natural Ways to Help with ADD

Cerebral folate deficiency in Down syndrome


Kris said...

Good post, Andi!

One thing I am trying to figure out is that since the MTHFR mutation is hereditary and women AND men can have it, then it is likely that my son has it. So what if he can use the folinic acid efficiently enough?

I have read that Metafolin (L-methylfolate) and/or 5-MTHF might be better than folinic acid. What do you think?

The other important components to the SAME cycle are B6, B2, Betaine (aka trimethylglycine or TMG). I am considering adding all of these as well. Not sure on the doses yet though.

Kris said...

One other comment related to reflux - reflux medications significantly reduce the body's ability to absorb B12 - it has to be broken down by stomach acids in order to be used. If one is on reflux medication, ingesting B12 is not going to be very helpful.

The B12 that dissolves under the tongue and/or B12 shots are a much more effective way of getting the vitamin into your system.

Andi Durkin said...

Yes, I take Metafolin and folinic acid. Jett is able to take straight folinic because he only has one of the mutations. And yes, B6, B2, Betaine (TMG) are important as well. Jett and I both will be taking TMG. (I have the bottle) but haven't figured out how much yet. I've posted this info on the Tests and Treatment for Moms post.

Liora (Lourie Collins) Pearlman said...

hi, Andi is there any reason NOT to give our kids with DS the Metafolin? Why do you give Jett the folinic?

I have been using one product for Etel and myself, and it is time to reorder. But you got me second guessing myself about why I chose it in the first place for her! (Solgar 800 mcg a day from iherb.com here http://www.iherb.com/Solgar-Folate-Metafolin-Folic-Acid-800-mcg-100-Tablets/13961?at=0 it's a much better price than the FOlapro! They also have 400 mcg a day from Solgar- we use a wooden mortar and pestle to crush the tabs.) THANKS Liora

Liora (Lourie Collins) Pearlman said...

And p.s. we are both taking TMG. Etel at around 300 mg a day of powder, not carefully dosed- and me a different pill form at the dosage on the bottle at 500 mg/day.

Her naturopath had originally recommended 250 mg TMG a day, but Etel has grown in size since then.

Andi Durkin said...

I give Jett both, just in case! So, no, I don't know of a reason NOT to give Metafolin.

Michelle Mason Rocks said...

I learned almost 2 years ago I have epilepsy. At the same time, I learned I had a severe B12 deficiency. I've been taking B12 shots, which have improved things a LOT, over 90% seizure reduction. (http://michellemasonrocks.blogspot.com/2015/12/how-i-manage-seizures-without-drugs.html) Which got me to thinking about the other 10%...if it was low B12 causing my seizures, why weren't they gone completely? And why did I have low B12 anyway? I'm not vegetarian, I eat meat daily. Then I learned if you are low in folate, it will cause low B12, and then I learned about the MTHFR mutation and folinic acid. Which brought me to your blog. Very well written, GREAT information, HUGE thank you! You've done amazing work and are helping people.

Unknown said...

Hi Andi, how much folinic are you currently giving Jett? And how much B12. I know for those without T21 the ratio should be twice as much B12. We have started increasing the folinic with our nearly 8 year old son with DS, and are seeing amazing results. His moods have improved hugely, his limited speech is expanding and clarity is improving, and his behaviour is much improved too. I'd really appreicate your input as to how much of each of the folinic and B12 to get him up to. He's currently on 3200mcg folinic, 400mcg methyl folate and 1000mcg B12. Thank you

Unknown said...

Hi Andi, thank you for your great posts. I would really appreciate some info on how much B12 and Folate/Folinic Acid to give our son, nearly 8, born with DS. He is nearly 20kg. I have been slowly increasing his folinic, now up to 3200mcg a day. He also has 200mcg methyl folate and 500mcg B12 in a combined methylated B complex. Since increasing his folinic we are seeing obvious improvements in his behavior and speech - from unclear single words only, to improving clarity and multi word sentences.

Andi Durkin said...

Hi Angela!

Glad to hear that you are seeing progress from using folinic acid. Please see see the post Cerebral folate deficiency in Down syndrome http://dsdaytoday.blogspot.com/2013/03/cerebral-folate-deficiency-in-down.html for how I originally dosed it for Jett.

Now, I muscle test to see exactly what he needs, when and for how long. Youtube has many good videos on how to muscle test. Make sure you are well grounded before testing. :)

Unknown said...

Hi Andi, Thank you so much for all of your research and generosity in sharing it with us. I am in my first trimester and our baby tested positive for Down Syndrome. I'd like to do whatever I can to help promote brain development. I am currently taking the 3 a day Garden of Life Vitamin Code prenatal which contains 800mcg Folate and 6mcg Vitamin B12. In your experience with research, would you mind sharing your opinion on what would be a good brand of Folate or Metafolin or folinic acid as well as Vitamin B12 supplement I should take per day? Also what total intake per supplement would be ideal per day?

Andi Durkin said...

Hey Julie!

I like VeganSafe B12 and I still like the folates that I listed in the post and in the store. (Just go to "Shop" and folate, etc to see the list.)

Andi Durkin said...

And, Julie, I'd muscle test to see how much you need exactly. You can do it yourself or go to a chiropractor or to someone who does NAET.

Unknown said...

Thank you so much Andi! And thank you for the incredible amount of work and research you have done for your brother. You're a remarkable person. So far, based on what I've been reading, I'm thinking of going with the following:

1) 2 to 2.8 mg of B12- the methylcobalamin in by sun force or the VeganSafe B12 you suggested.
2) 4.4 to 5 mg per day or a 1/2 and 1/2 mix of folinic acid/calcium folinate and L-5-MTHFR and choosing from the list of vitamins you suggested- maybe going with the Neurobiologix Methyl Folate with Activating Co factors just in case I have any adverse symptoms.
3) 50 mg of B6- still trying to find a good source for this. If you have any suggestions I'd love to hear them?

Since I'm ending my 1st trimester, and feeling rushed, I'd like to start taking them right away. I'll try the muscle testing as well. I'm just thinking that taking the maximum right now might be the best way to go, just in case. From what I can tell, none of these vitamins at these levels would have any adverse affects on my or the baby's health.

Do I sound like I'm on the right track for this, or would you suggest a different direction?

Andi Durkin said...

It sounds like you're on the right track, Julie. I haven't found a natural source of B6 other than what's in MegaFood Balanced B or New Chapter, so you could go with a reputable company like Kirkman or Life Extension for the synthetic B6. I muscle tested fine for Vitacost brand B6.

kikilaroo34 said...

I have a 7 yr old that has been on nothing, can you do me a recommendation to start her off? How much, what form, excetera

@KeleChy said...

Welldone Andi for what you have been doing. Great one indeed. My baby is 8months old. He is not on any vitamin or rather supplement yet. But I just ordered Nutrivene D, for him although it has not arrived. I am in Nigeria and our health system here is not favourable for kids with DS. Even the laboratory test that was carried out by PATHCARE laboratory in Abuja, Nigeria, did not come with any report. They just wrote T21. My questions are: any other supplements/vitamins can you suggest that he is supposed to be taking apart from the Nutrivene? Besides, am I supposed to be taking any supplement myself to help him? Meanwhile, I noticed that the DS shop website has been temporarily unavailable for a while now. Thank you.