Vol. V · ii Foundations 2 min read
Why Am I Always Tired? B12, Folate and Methylation
The most common cause of low energy we see is not exotic. It is also the easiest to correct.
Methylcobalamin is the active form of B12 — the form cells use without conversion. It sits at the centre of methylation, the reactions that build neurotransmitters, maintain nerve tissue and recycle homocysteine. Deficiency is common, under-diagnosed, and produces symptoms unglamorous enough to be attributed to almost anything else.
What methylation is, briefly
Methylation is a set of reactions that attach a small chemical group to other molecules. It sounds abstract, and it underpins building neurotransmitters, maintaining the myelin around nerves, regulating gene expression and recycling homocysteine.
B12 and folate are central to it. When either runs short, the consequences are diffuse rather than specific, which is exactly why the problem gets missed.
Why it goes undiagnosed
Partly because serum B12 is a poor test. It measures what is circulating, not what has reached cells and been used, so a result within range does not reliably exclude a functional deficiency.
Partly because the symptoms are unglamorous: fatigue, low mood, brain fog, cold hands, pins and needles. Each is easy to attribute to stress, age or a busy period, and the diagnosis often arrives only after other things were ruled out.
It is worth ruling out before you treat anything more interesting.
Absorption is the usual failure point
Most people are not short on intake. They are short on absorption, which depends on stomach acid and intrinsic factor and declines for several ordinary reasons.
Age reduces it. So do metformin, long-term reflux medication and low stomach acid generally. This is why we dose intramuscularly rather than orally when the history suggests malabsorption u2014 an oral dose that is not absorbed is not a dose.
Why it is worth ruling out first
It is inexpensive, it is safe at the doses used, and when it is the answer patients usually know within about two weeks. That combination makes it a sensible thing to exclude before anything more interesting is considered.
It also sits alongside the other common causes of the same complaint u2014 thyroid, iron, sleep u2014 which is why it is read as part of a panel rather than alone.
Common questions
Can low B12 make you tired even if the test is normal?
Yes. Serum B12 measures circulating levels rather than what has reached and been used by cells, so a result within range does not reliably exclude a functional deficiency. This is why it is read alongside folate, iron and thyroid rather than alone.
Why injections rather than tablets?
Because the usual failure point is absorption rather than intake. Age, metformin, reflux medication and low stomach acid all reduce it, and an oral dose that is not absorbed is not a dose.
How quickly does B12 work?
When deficiency is genuinely the cause, most patients notice a change within about two weeks. If nothing changes over that period, the fatigue likely has another explanation worth pursuing.
Educational — not medical advice.