By the time you read this, I will be basking in the sunshine of Valencia at the ECU’s 2024 conference.
Whenever I lecture to new groups, I am always looking to take previous lectures and make them even more simple, more straight line to clinical actions and solutions.
We are shortly going to have a vitamin B12 flow chart available to order as part of our infographic series, plus on the flip side of that A4 sheet will be a B12 blood level and symptom guide.
So let’s take a look at the latter in all its glory.
One of the challenges with diagnosing B12 functional deficiencies is that blood testing is simply not a reliable way to rule out deficiency.
From NHS guidance:
It can rule deficiency in, but not out.
This is in direct opposition to vitamin D where we have a reliable blood test, AND as the blood levels go down, symptoms strongly go up, it is a relatively linear response.
If patients are below 25 noml/L 25(OH) D3, they will be symptomatic (pain, stiffness, fatigue, depression/anxiety) and they will know they are not well.
The challenge is for B12, a “normal” blood test (anything over 148 pmol/L ish but under 500 pmol/L can still be deficient on a cellular level.
Remember, a B12 blood test tells you what is in the blood, but the point of B12 in the blood is to transport it into the CELL.
B12 holds a rate limiting effect on two key enzymes that work within the energy cycle and the methylation cycle (Remember methylation is how we make new molecules, like myelin, creatine, DNA for news cells and break down or converts others things like hormones, toxins, serotonin to melatonin etc).
So, if a total B12 blood test is under 148 pmol/L (200 ng/L), then this confirms deficiency and FYI they will be symptomatic at this level, albeit the forms of symptoms and severity varies.
But there is a grey/intermediary zone that exists (148-500 pmol/L ish), where patients may be deficient on a cellular level (in energy cycle and methylation) and wildly symptomatic including overt bilateral neurological symptoms, cognitive symptoms, severe fatigue (usually in the absence of anaemia) etc.
This is not my opinion, this is part of NHS guidance.
Where exactly grey zone finishes we do not know, but we have chosen 500 pmol/L (677 ng/l).
So at any point in this range, if the patient has symptoms, we always treat.
The reason?
Missing B12 deficiency can be lethal and give permanent disability.
Just ask this young lady, who is currently suing the NHS for ending up in a wheel chair most of the time.
Patients can have NHS “normal” blood levels in the 200-500 pmol/L and have gross deficiency with overt symptoms of demyelination.
Hence the chart:
So, to the protocol.
I now advise starting all patients on B12 liposomal in the HYDROXOCOBALAMIN form, 500 mcg (0.5 ml) in the AM.
This is for a number of reasons, chiefly to keep it simple.
Also, because as a liquid, if the patient has anxiety, you can start with lower doses – a few drops daily and slowly build up to 500 mcg daily in the AM over a few weeks.
Also, hydroxocobalamin binds the gas nitric oxide, which is part of inflammation and increases blood flow during inflammation – especially important in migraine.
Note HYDROXOCOBALAMIN is the same INACTIVE form used in NHS injections.
Our body will usually convert this into the two active forms, METHYLCOBALAMIN (for use in the METHYLATION cycle) and ADENOSYLCOBALAMIN for use in the energy cycle.
Previously we went straight for the active forms, because of concerns about poor conversion, and while this is still a consideration, I think this occurs in a minority of patients.
So, for simplicity’s sake and for the dosing flexibility of a liquid, we start with HYDROXOCOBALAMIN liposomal and then if we fail to get a response, then we can switch to the directly active forms using our ACTIVE B12 SUBLINGUAL.
One other benefit is LIPOSOMAL B12 is encapsulated within a fatty globule, then is passively absorbed into the blood from the gut,
AND even more importantly, also goes straight into the cell, bypassing any B12 cellular transporter issues.
This is an issue for a minority of very ill patients, who have lovely high blood levels, because they cannot get it into the cell to spin the wheel of energy and methylation – thus are highly symptomatic but have “normal” blood levels.
Then we look at the patients’ symptoms, and we make a decision about whether we want to primarily support METHYLATION or ENERGY or bit of both.
KEY POINT: there is no right or wrong here, there is only clinical judgment and trial period of supplementation. If it doesn’t move the needle within 2 weeks (at a push 4 weeks), we change and try again.
If the symptoms are neurologically dominant (pins and needles, pain, cognitions, depression), or cell turn over (mouth ulcers, sore tongue, poor healing), then we use METHYL B HERO, which as the name suggests is specific to methylation – B12 in methyl form 600 mcg, active folate 800 mcg, B6, B2 and Tri-methyl glycine (TMG) – all for increasing methylation.
If the symptoms are fatigue dominant, then I tend to use the ONE A DAY ESSENTIAL MULTI, which has all the B vitamins needed to spin the energy wheel.
Note, it includes B12 methyl form 400 mcg, active folate 400 mcg , B6 35 mg and B2 50mg, (but no TMG) so it does support methylation, but less.
Thus, if the patient has a combination of symptoms across methylation and energy, I generally try ONE A DAY ESSENTIAL MULTI first.
Again, if that doesn’t move the therapeutic needle, change it.
Now you might be thinking well if they have B12 in the METHYL B HERO or ONE A DAY ESSENTIAL MULTI, why do they need the HYDRXO B12 liposomal?
The answer is because if the reason they are deficient is that they cannot absorb B12 from diet, then giving them supplements that need absorbing in the gut is not going to work well.
You could argue that with huge dose you might get enough in, but “might” isn’t something I would not want as part of my healthcare if the consequences are permanent disability.
We now have the technology of LIPOSOMALS and SUBLINGUALS, so we do not need to risk a non-response to the swallowed caps – they go directly into the blood stream.
Within 2 weeks, most people will feel a significant change, 4 weeks at a push if very poorly.
If they do, then you can hold them at that dose let symptoms settle, and then you can begin to withdraw the B12 liposomal down to x2 a week, and assess if the clinical changes are maintained.
If they are, try dropping the B12 HYDRXO liposomal completely and if they still maintain the changes, then it wasn’t a big absorption issue and they are fine to take the METHYL B HERO or ONE A DAY ESSENTIAL MULTI long term.
If with the initial drop from daily to x2 week or from x2 week to none, they lose some changes, then simply push it back up, regain the benefits and the absorption issue is confirmed.
If you get a partial response or non-response to either the METHYL B HERO or ONE A DAY ESSENTIAL MULTI, then simply swap.
Same also with the HYDROXO B12 lipsomal with the ACTIVE B12 SUBLINGUALS.
For those anxious patients
Here is the full protocol, we will have these available to order free of charge soon
