How to Use the B12 Protocol (Part 3): Vitamin B12 and Folate

This blog post is the final part of a three-part series on how to use the B12 Protocol.  It is recommended that you implement Part 1 and Part 2 before continuing with this post.  In this series, we have been covering the steps involved in fully implementing the B12 Protocol as a means of improving the Trifecta of health.  I will be repeating some information from previous parts where appropriate.

While there is no single correct order of implementing the vitamin B12 Protocol to repair methylation capacity, redox capacity, and mitochondrial health, this series has emphasized the most common order of doing it.  Doing the steps in a different order is more likely to result in temporary, but unpleasant, side effects as a result of increasing demand for metabolic processes that may require some preparatory steps to be in place.

If you implement all of the steps of the B12 Protocol, it should not have any different result in the end, and in that context, the order is not significant from a final result standpoint.  However, to reduce or avoid negative symptoms while improving the components of the Trifecta, it is imperative that you make changes by listening to what your body (and lab testing) tells you.  This order is the well-traveled path, if you will.

Here is a succinct biochemical conclusion of what was accomplished by implementing Step 1 and Step 2 of the B12 Protocol:

Step 1)  Thyroid function has been optimized by addition of iodide and selenium, which upregulates the activation of vitamin B2 into flavin mononucleotide (FMN).  This is one of the two active forms of the vitamin.  FMN acts as a coenzyme in several key reactions in the body, including Complex I of the electron transport chain, which is essential for converting food into usable energy.

Step 2)  The second step involves further optimization of functional vitamin B2 status by providing molybdenum and additional vitamin B2.  The second active form of vitamin B2 is called flavin adenine dinucleotide (FAD) and requires a molybdenum-containing enzyme for its production in the body.

While FAD acts as a coenzyme for many important reactions in the body, one of the primary functions of optimizing FAD is for increasing activity of the MTHFR enzyme.  This enzyme is heavily involved in the regulation of cellular methylation capacity.

So with the above biochemistry in place, we are now ready to implement the final step of the B12 Protocol.

 

How Do I Know if I'm Ready for Step 3?

Optimally, addition of iodide, selenium, molybdenum, and vitamin B2 will prepare the body for Step 3.  There are some situations where lab testing informs us that the previous steps require more adjustment in dosing before we have optimized thyroid output and vitamin B2 activation.  Does that mean we need to wait for labs to be in ideal ranges before progressing to the final step?  In most cases, no.

In some people, the body may need several months of nurturing before they will notice correction of the labs involved with the first two steps.  Even still, it is usually best to get started implementing Step 3 while waiting for these processes to adjust.  You may need to extend the duration of implementation of Step 3 when that is the case.

Advancing to Step 3 should only be avoided altogether if it causes intolerable side effects or regression without counterbalancing progress.  If that is the case, adjust your doses of Step 1 and Step 2 components, allow the body to re-establish baseline, and attempt Step 3 again.

When the first two steps have not been adequately addressed, it does not mean that your body is incapable of processing vitamin B12 and folate.  It simply means that the effects of these vitamins will not be maximized until those conditions are better satisfied.

 

Step 3: Reactivating the Methylation Cycle with Vitamin B12 and Folate

With the above preparatory work in place, the body is now more capable of utilizing folate and vitamin B12, allowing the full potential of these nutrients to be unleashed.  The third and final step, therefore, involves introduction of vitamin B12 and folate.

At Spectrum Sciences, we emphasize that vitamin B12 serves both CoEnzymatic Roles and Pharmacological Roles.  More on that distinction later, but for now, we will focus on one of the coenzymatic roles.

 

The Synergy of Vitamin B12 and Folate

With the activity of MTHFR primed for optimal function by following the first two steps of the protocol, the body is capable of producing methylfolate from dietary folate and supplemental folate.

This is a necessary condition for the body to make use of vitamin B12.  With folate’s methyl group, vitamin B12 is able to serve its coenzymatic function in the reaction catalyzed by methionine synthase (MTR), which is to transfer this methyl group to homocysteine, forming methionine.  Let me explain the importance of this reaction through analogy.

The progression of metabolic intermediates within the methylation cycle can be compared to the movement of a hand around the face of a grandfather clock. For this analogy, however, let's assume we only have a single hand that tells us the time. For this clock to function well, the hand must move around the clock in a smooth, steady fashion. If the hand gets stuck at any position around the clock, it will not function well. 

In this depiction of the methylation cycle below (courtesy of Genova Diagnostics), each enzyme is represented by a blue rectangle with its abbreviation in white letters.  At the 1 o'clock position is MAT; at the 3 o'clock position is where MT enzymes are represented; at 5 o'clock is AHCY; and at the 9 o'clock position is where MTR (which works in tandem with MTHFR) sits.

Our "methylation cycle clock" is designed in such a way that its hand is susceptible to getting stuck at the 9 o'clock position. This is an intelligent design, but I won't get into those details here - suffice to say we want the hand to move past 9 o'clock smoothly. The enzyme MTR sits at the 9 o'clock position, and this is where the addition of vitamin B12 and folate exert their influence on methylation. The job of MTHFR and MTR is to work in tandem to prevent the hand of the clock from getting stuck at the 9 o'clock position.  This keeps the methylation cycle in constant flux, providing a robust supply of methyl groups for the many biochemical reactions that depend upon this availability.

The clock can get stuck in other positions as well, but as I said before, the design is such that the 9 o'clock position is "stickiest". The way that the B12 Protocol improves methylation can be compared to the way oiling the gears of the clock prevents the hand from getting stuck where we see those tendencies. In a bit of humorous metaphor, by oiling your body with B12, you are oiling the gears of your methylation cycle clock.

 

What are the functions of methylation reactions in the body?

Methylation capacity is essential for many chemical reactions in the body to occur, including but not limited to:

• Epigenetic regulation of gene expression
• Embryonic development
• Regulation of cell life cycle (goes awry in cancer)
• Energy production and regulation, including synthesis of phospholipids, carnitine, and creatine
• Redox regulation

This list includes all non-negotiable items for the continuance of life.  If methylation capacity suffers, our body's ability to stave off disease associated with dysfunction in these processes is diminished.  It also determines, in part, the ability of a pregnant mother to sustain the life and health of the unborn child.

Vitamin B12 and folate are essential components of maintaining this cycle.

 

So which is first, Vitamin B12 or Folate supplementation?

Before answering this question, it is important to revisit the necessity of transdermal vitamin B12 for serving this purpose.  Because vitamin B12 has a very limited capacity for absorption in the human gut, dietary provision and oral supplements provide only meager amounts (especially in a person with a damaged gut) when we are looking to maximize coenzymatic activity of this vitamin.  To achieve supraphysiological levels of active B12, a transdermal formulation is the only convenient, non-invasive way of achieving that.

Furthermore, at Spectrum Sciences, we believe that a significant portion of the benefit from supraphysiological doses of vitamin B12 comes from what we call Pharmacological Roles of vitamin B12, and these effects can only be attained from very large doses – much more than what the body can ever obtain from the oral route.

The answer to whether you should begin with vitamin B12 or folate depends on how much folate you are intending to use.  In a study that analyzed the folate metabolism of children with autism, it was determined that a majority of them are seriously disadvantaged by the presence of autoimmunity directed at the folate receptor.  With this system damaged, as little as 1% of circulating folate can enter the cell.  In these cases, pharmacological doses of reduced folate are needed to correct the intracellular levels of folate.  However, this has to be done carefully to prevent a biochemical situation known as methyl trapping.

To simplify the concept of methyl trapping, we can understand it as a situation where methylfolate is trapped in a portion of the folate cycle, making it unavailable for other critical functions like DNA synthesis.  This can lead to symptoms of functional folate deficiency (listed below).  Taking high doses of folate supplements without vitamin B12 can hinder methylation, so we usually suggest that vitamin B12 be implemented before supplementing higher doses of folate.  Nutritional doses of folate (that which can be obtained from diet, or the amount contained in the recommended dose of Protocol Support), is not likely to cause these problems with methyl trapping.  However, it is advised that you avoid higher doses of folate until the functional vitamin B12 deficiency situation has been corrected, which includes the first two steps of the B12 Protocol and the vitamin B12 portion of Step 3.  Seek the advice of your personal physician for the order that suits your individual situation.

When we do begin to introduce vitamin B12 and folate, it is still important to wait 1-2 weeks between dosing adjustments as suggested in previous steps based on how long it takes most people to feel the effect of a particular nutritional change on their mind and body.  By allowing enough time to become conscious of the effect of a change, it gives the user a better understanding of how each product impacts them, which can be used to inform dosing.  While most people find that 8-9 drops of Activated B12 is sufficient to correct a functional vitamin B12 deficiency, use lab testing to help inform your optimal dosing.  The organic acids test and methylation panel are your best lab options for assessing vitamin B12 and folate status.  Correcting vitamin B12 insufficiency is almost always the more challenging component.  Sometimes, functional folate deficiency is corrected without specifically focusing on supplementing folate.  Leafy greens, eggs, and liver are the best dietary sources of folate and may provide adequate amounts for some people.  As mentioned before, however, vitamin B12 cannot usually be repleted through diet alone.  Therefore, we provide some examples of how you might go about implementing Step 3 of the B12 Protocol.

Please note that the term “folate” includes any form that fulfills the vitamin role of this substance, including dietary folate (dihydrofolate), folic acid (synthetic supplement), folinic acid (reduced form of folate), and methylfolate (another reduced form of folate).

Spectrum Sciences has concluded that folinic acid (not folic acid) is the best supplemental form of folate to include in the B12 Protocol.  Folinic acid is a highly bioavailable, reduced form of folate that does not interfere with folate uptake by cells.  Folic acid, on the other hand, does not occur in nature, and though healthy people can use up some of their body’s reduction potential to convert folic acid into useable folate, many people with complex health challenges related to methylation capacity and redox capacity are taxed by folic acid supplementation.  Practitioners who specialize in helping children with autism have noted that folic acid is inferior to folinic acid, and in some cases, causes worsening of functional folate deficiency symptoms.  Folic acid may downregulate the enzyme that reduces dietary folate (DHFR) and it may also compete with reduced folate for the reduced folate carrier (RFC), potentially blocking active folate uptake.  The moral of the story is to avoid folic acid.

While methylfolate supplements are also a bioavailable, reduced form of folate, and offer a potential alternative option for some, experience has taught us that many children do not respond favorably to methylfolate supplementation.  This may be especially true if it is given before their functional vitamin B12 deficiency has been corrected.  The negative effects are usually dose-dependent.

For these reasons, Spectrum Sciences has included folinic acid (NOT folic acid or methylfolate) in our Protocol Support multivitamin.  The dosage per capsule is only 67 mcg, which allows the user to avoid high doses of this vitamin that would likely lead to methyl trapping if utilized before the functional vitamin B12 deficiency situation has been corrected.  If you choose to include folate as a single supplement, we suggest you source folinic acid.

Your progression with Step 3 can take on a few different approaches, depending on personal needs, preference, and individual response.  As was done for previous steps involved in this blog post series, some examples are tabulated below.  Assume that Week 1 is referring to any week after you have completed the introduction phase of Step 2.

 

Simplest B12-only approach #1 (full introduction of Activated B12 with no supplemental folate):

	Activated B12 (drops)	Folinic Acid (mcg)
Week 1 and thereafter (daily)	8	0

This approach works well for people who do not typically have difficulty with dosage adjustments.  It is only recommended as an option for those who have optimized their thyroid output and vitamin B2 activation as evidenced in their labs.  For more sensitive people, and for those who have implemented the first two steps but may not yet have their biochemistry optimized, the other approaches that follow might be better choices.

 

B12-only approach #2 (Titration of Activated B12 with no supplemental folate):

	Activated B12 (drops)	Folinic Acid (mcg)
Week 1 (daily)	2	0
Week 2 (daily)	4	0
Week 3 (daily)	6	0
Week 4 and Thereafter (daily)	8	0

This approach may work better for more sensitive people, and for those who have implemented the first two steps but may not yet have their biochemistry optimized.  Like the previous example, supplemental folate is not included, because not all people need to include it.  The organic acid test and red blood cell folate can inform whether supplemental folate is needed.

 

B12+Folate approach #1 (full introduction of Activated B12 followed by titration of folate):

	Activated B12 (drops)	Folinic Acid (mcg)
Week 1 (daily)	8	0
Week 2 (daily)	8	67 – 200
Week 3 (daily)	8	133 – 400
Week 4 (daily)	8	200 – 600
Week 5 and Thereafter (daily)	8	267 – 800

*the typical doses of Activated B12 and Folinic Acid are the same for adults and children, but defer to the recommendations of your personal physician.  Studies involving children with autism found that 800 – 1600 mcg of folinic acid in conjunction with vitamin B12 were used to normalize methylation parameters.  Here is one of those studies.

This approach may work better for more sensitive people, and for those who have implemented the first two steps but may not yet have their biochemistry optimized.  This example, in contrast to the previous examples, does include supplemental folate, and can provide an additional boost to the methylation cycle for those who need the extra folate. 

 

Optimal Dosing

These examples are based on common usage rates, however, there is no way to predict how many drops of Activated B12 you will require or how much folinic acid is needed to optimize your methylation cycle. Let your symptoms and lab results dictate that.

After maintaining steady doses for at least 4 weeks, then submitting an organic acid test (OAT), we can look for markers of functional vitamin B12 sufficiency and functional folate sufficiency.  That is a detailed topic for a future post.

The symptoms of functional deficiencies in these two vitamins are extremely difficult to differentiate symptomatically.  For practical purposes, we will use the same set of symptoms to assume a functional deficiency in both vitamins.  If we base functional vitamin B12 sufficiency and functional folate sufficiency on symptoms, we should note the absence of, or improvement in the following:

• Neurological symptoms, including numbness, tingling, muscle weakness, balance problems, difficulty walking, confusion, memory loss due to poor nerve myelination, which requires adequate methylation capacity
• Gastrointestinal issues, including constipation or diarrhea due to poor mitochondrial function, in part from poor oxygen delivery and in part from poor Krebs Cycle function
• Psychological effects, including depression, mood swings, irritability, dementia, psychosis related to poor energy production in the brain from the same causes as those that bring on gastrointestinal issues
• Physical symptoms, including fatigue, weakness, pale or yellowish skin, loss of appetite, weight loss, sore or red tongue related to poor red blood cell production (megaloblastic anemia, which is characterized by large, dysfunctional red blood cells that cannot effectively carry oxygen)

Correcting the functional deficiencies will lead to a gradual reversal of these symptoms.  The more severe these symptoms are, the longer they will take to see improvement.  Also, the older the individual suffering these symptoms, the longer they will take to see improvement.

Every person will benefit from correcting their functional vitamin B12 deficiency in somewhat different ways and to differing degrees.  The B12 Protocol exists for anyone with a functional vitamin B12 deficiency, but one of the most stark examples of dysfunction in vitamin B12 metabolism is witnessed in children with autism.

Use of vitamin B12 has been used as a treatment of autism for over 20 years, and much of what we have learned about the vitamin and the metabolic processes it governs comes from studying its use in that context.  Two decades of observation by thousands of parents around the world have reported many similar effects.  The benefits I am about to list just happen to be the most common.  This does not mean every child has experienced all of these (or any of these) or that these are the only benefits that can be attributed to this treatment.  Those commonly reported benefits of vitamin B12 treatment include:

• Improved cognition
• Reduced fatigue
• Increased affection
• Increased alertness
• Improved mood
• Increased appetite
• More assertive
• Increased desire to communicate verbally
• Improved verbal expression, putting more words and/or ideas together
• Improved receptive language
• More age-appropriate behavior
• More appropriate play
• Better eye contact
• Improved motor skills
• Improved bowel function
• Reduced anxiety
• Understanding of cause and effect
• Less rigid about routine
• Less clumsy
• Increased compliance
• Improved comprehension
• Reduced compulsive behavior
• Increased concentration
• More conversational or back-and-forth interaction
• Improved allergy symptoms (such as dark circles under the eyes)
• Better at following directions
• Understanding choices
• Reduction in appearance of skin rashes, including eczema
• More engaged with others and less in their own world
• Begin to have rational fears and begin to let go of irrational fears
• Understanding of feelings
• Calmer and less easily frustrated
• May begin to sing for the first time, or increased interest in singing
• Growth spurt
• Ability to generalize is improved
• Improved gesturing
• Enjoying humor and begining to understand humor better
• More imaginative and creative
• Improved imitation skills
• Improved immune system
• Improved independence
• Initiation of play or interaction with others
• More inquisitive
• Broader interests (less restricted to a singular obsession)
• Learning with reduced requirement for prompts
• Improved memory
• Open to trying new things
• Improved quality of sleep
• Increased formation of opinions
• Pays more attention to people
• Improved reading skills
• Makes more requests
• Quicker response time (less time required to process)
• Improved ability to retain what is learned and build upon previous knowledge
• Less fidgety
• Improved time, place, and space awareness
• Improved prosody or tone inflection (speech is less monotone or robotic sounding)
• Increased answering of questions, including yes and no questions
• Increased asking of questions such as “what, where, who, when, and why” or answers with "because"

 

Here I have listed 58 commonly reported benefits of correcting a functional vitamin B12 deficiency in children with autism.  If you are following this protocol in that context, please do not expect your child to demonstrate all 58 benefits in the first couple months of incorporating the B12 Protocol.  But in five years, should you stick it out, I would be willing to bet that you will look back on where your child was when they began this therapy and where they are now, and can say that most if not ALL of the 58 listed benefits will be witnessed to varying degrees in your child.

If you are an adult living with a functional vitamin B12 deficiency condition, you likewise should feel many of the relevant symptoms gradually resolve as time unfolds.

Improving neurological development with the B12 Protocol is a long-term process, and many good things will be witnessed by those who are patient enough to continue through the seemingly uneventful developmental plateaus.  Rest assured, change is happening during those dull periods, perhaps only at the metabolic level, waiting to manifest physically at the appropriate time.

 

Using Symptoms to Inform Dosing and Pace of Titration

Just as you did when introducing Step 1 and Step 2, note how you feel with each dosage change - if it is positive, you may continue to test the effects of increasing the dosage until you either notice a regression in your health or fail to notice any additional change from increased intake.  At that point, revert to the dose you previously tolerated and noted your last improvement from.  I suggest you keep detailed, written notes in a journal, because memory can be a lousy informant!

It is our goal to maximize the transformative effects of this protocol and would be great if we could avoid any negative "growing pains", however, healing in any capacity often involves some discomfort, and we would be remiss to neglect mention of this possibility.

At Spectrum Sciences, we like to frame any negative adjustments as our body informing us of how to help us heal.  In that sense, negative symptoms can be tremendously informative, though admittedly physically challenging.

If you experience a feeling like you are having a bit of an adrenaline rush that you believe may be due to protocol supplements, you may experience some relief by simply increasing potassium intake.  Since this is usually a wise health choice anyhow, it makes sense to try that approach first before making any adjustments to any of the protocol supplement doses.

It is best to take symptoms and lab testing equally into consideration when deciding on how to dose Activated B12 and Folinic Acid.

 

Final Thoughts

While this blog post has not covered all of the ins and outs of reactivating the methylation cycle with vitamin B12 and folate, it covers a lot of ground in that area.

If you need additional help navigating the use of Activated B12 Oil and Folinic Acid in the context of the B12 Protocol, you can arrange one-on-one coaching.

We hope you have learned something useful from this blog post series.  It will be updated as more is learned about how people respond and as new product offerings become available.  We are excited about what this next year has in store!

Have a topic you would like covered?  Do you have input to give or a story to share?  Please feel free to contact us.  Your input helps us improve our educational material and product offerings.  It also gives us motivation to continue doing what we’re doing.

Thank you for being part of our B12 community.