vitamin · for chronic fatigue
Vitamin B12
B12 is needed for the reactions that turn food into energy inside your cells.
Say that in clinical terms
B12 is a cofactor for methylmalonyl-CoA mutase and methionine synthase, essential for mitochondrial energy metabolism and the citric acid cycle. Deficiency impairs fatty acid oxidation and myelin maintenance, causing profound fatigue.
How strong is the research?
A pooled analysis of 16 trials in 6,276 people found no improvement in thinking or mood.
6 papers read, 4 supporting, 2 against.
Tested as: hydroxocobalamin
Who was studied: The cited paper is about infant brain development and contains no adults at all.
A proper search found trials of this compound, but not in the form named here — hydroxocobalamin. Evidence for one form is not evidence for another.
How much to take
daily (sublingual preferred)
1000–5000 mcg
Sublingual bypasses potential absorption issues. Essential to check B12 and MMA levels. Higher doses for documented deficiency.
Before you take it
- No NIH ODS or IOM Tolerable Upper Intake Level (UL) has been established for vitamin B12 in any form; the IOM found no adverse effects attributable to excess intake from food or supplements in any population studied and set no UL.
- Metformin significantly reduces B12 absorption by impairing calcium-dependent membrane action in the terminal ileum; patients on long-term metformin are at elevated risk of B12 deficiency and should have serum B12 monitored periodically.
- Proton pump inhibitors (PPIs) and H2-receptor antagonists reduce gastric acid secretion needed to release protein-bound dietary B12, thereby reducing absorption from food; this effect is substantially less pronounced for free supplemental B12 forms.
- High-dose folic acid supplementation can mask the hematological signs of B12 deficiency (megaloblastic anemia), potentially allowing neurological damage from covert B12 deficiency to progress undetected.
- Rare anaphylactic reactions have been reported with parenteral (injectable) B12 preparations; no equivalent hypersensitivity risk has been established for oral or sublingual supplemental forms.
- Individuals with Leber's hereditary optic neuropathy should avoid high-dose cyanocobalamin; methylcobalamin is the preferred supplemental form when B12 supplementation is clinically indicated in this population.
- Patients attributing chronic fatigue to B12 deficiency and self-supplementing may delay evaluation of underlying causes such as hypothyroidism, iron-deficiency anemia, sleep apnea, or depression, which have distinct and effective treatments.
When to take it
Best taken: morning
What we make of it
The citation is a paper about brain development in infants.
The detail
The identifier resolves to a 2008 review of what B12 deficiency does to infant neurodevelopment. It contains no adults and nothing about fatigue.