Folic acid and vitamin B12 deficiency in people
What it found
In people with low vitamin B12, having high folate levels was linked to worse thinking test scores and higher blood markers of B12 shortage.
High-dose folic acid supplements also lowered B12 levels in patients.
What they found
Studies in people
Thinking and memory scores
Older adults with low B12 and high folate scored worse on thinking tests than those with low B12 and normal folate. This pattern showed up in surveys from the United States, Australia, and Chile. One study in the United Kingdom did not find this link.
Blood markers rise together
People who were short on B12 but had high folate had higher levels of homocysteine and methylmalonic acid in their blood. These are signs that B12 is not working well in the body. People with normal B12 and high folate actually had lower homocysteine.
High doses lower B12
Patients with pernicious anemia or epilepsy who took 5 to 15 mg of folic acid daily saw big drops in their blood B12 levels. This happened after just 5 to 8 days and also after months or years of use.
Other findings
A possible explanation
The authors suggest that too much folic acid uses up the active form of B12 in the blood. It may pull B12 into the bone marrow to make new blood cells, or stop the kidneys from recycling it. This idea has not been tested yet.
What the authors conclude
- They say the evidence linking extra folic acid to worse B12 shortage is strong enough to act on, even without final proof.
- They advise doctors to check B12 levels more carefully in older adults, vegans, people with gut problems, and anyone taking high doses of folic acid.
- They warn doctors never to treat B12-related anemia with folic acid alone.
How it was done
Doctors once used large doses of folic acid to treat a type of anemia caused by low vitamin B12. This fixed the anemia but hid the real problem, letting nerve damage continue or worsen. The issue came up again when countries started adding folic acid to flour and cereals to prevent birth defects.
The authors gathered past studies and surveys looking at how folic acid and vitamin B12 interact in people. They looked at data from thousands of older adults in national health surveys, plus small groups of patients given high doses of folic acid for days to years. They also proposed an untested idea for how extra folic acid might drain B12 from the blood.
What it can’t tell you
- Most of the evidence comes from surveys taken at one point in time, which can show links but cannot prove cause and effect.
- The suggested way that folic acid drains B12 from the blood is only a theory and has not been tested in people or in lab settings.
Who paid
- Funding
- Funded by NIEHS NIH HHS; NIA NIH HHS; NIDDK NIH HHS (from the PubMed record).
- Conflicts
- Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JWM is co-author of a patent titled “Assay for Vitamin B12 Absorption and Method of Making Labeled Vitamin B12” (Patent Number: 8,202,507) issued to The Regents of the University of California (Oakland, CA), JWM is an associate editor for the journal Nutrition Reviews .
- Authors work at
- Rutgers University, USA; The Hebrew University of Jerusalem, Israel; Tufts-USDA Human Nutrition Research Center on Aging, USA
The paper
- Title
- Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?
- Type
- ReviewThe authors read earlier studies and describe what they found. It isn’t a new study.
- Evidence
- Studies in people
- Summarised from
- Full text
- Cite
- Miller JW, Smith A, Troen AM, Mason JB, Jacques PF, Selhub J (2024). Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?. Food and nutrition bulletin. doi:10.1177/03795721241229503Free full textPubMed 38987872DOI
Summary written 30 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error