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Folate Deficiency

Ruthy

I’ve suffered with fatigue since my stroke nearly 10 years ago. I’ve mentioned it to various medical professionals (my GP on numerous occasions relating to my cpsp mostly) and they have never suggested testing for vitamin/mineral deficiencies.
I visited my GP last week because I need to get to the bottom of my fatigue. Is it due to stroke/cpsp/migraine/medications? So I ask the Dr to start by booking me in for blood test to check for deficiencies.
I now know I am deficient in vitamin D and folate. I was curious to understand what the NHS meant when it said there may be complications if deficient for long periods so I did a bit of a Google and found out (bearing in mind I haven’t read around this quick search, so maybe do that first before mouthing off to your GP).
This is what I found,
Maintaining adequate folate levels is important for stroke survivors, as nutritional deficiencies can slow recovery and increase the risk of further complications.
And,
Central post-stroke pain could be exacerbated by folate deficiency as it can worsen neurological damage, increase inflammation, and contribute to oxidative stress after a stroke. Folate deficiency is linked to higher levels of the amino acid homocysteine, which can damage neurons and impair the brain’s ability to repair itself, potentially intensifying pain signals.
Hope this helps some of you who are tired of being tired.

EmeraldEyes

Ruthy I think that’s spot on. They checked my nutrient levels just a few months after my stroke. They found I was severly in foliate to so was prescribed a high dose of folic acid for 2 weeks and instructed to continue with an over the counter strength from then on. Which I have done now for nearly 5 years. Just a couple of days of being on them and the fatigue was greatly reduced, and the lethargy and heavy leg feeling I’d had just went. That’s when I really started improving my walking😁

I really do wish this blood test could be made a routine check for stroke survivors at the time of the stroke and then again at say, 6wks/3 months after the event.

Lorraine

Hedge

Ruthy
Helpful thank you

Pando

Also MTHFR mutation can be a cause of functional folate (B9) deficiency.
I asked AI How many people are affected. Bottom Line for the UK:
Roughly 1 in 10 people in the UK are homozygous for the C677T MTHFR mutation, and when you include all significant variant combinations (homozygous for either and compound heterozygotes), it likely affects over a third of the population. However, due to the lack of routine fortification, the potential clinical impact of these mutations on folate status may be more pronounced in the UK compared to countries that fortify their food supply. Most individuals remain asymptomatic unless combined with other genetic, dietary, or lifestyle factors.

Simon

Apparently the above means..

Click for an explanation

It is describing a very common genetic variant in folate metabolism, and suggesting that in a country without long‑standing folic‑acid fortification (like the UK until recently), this could make low or “borderline” folate status more common or more clinically relevant for a sizeable chunk of the population.[1][2][3]

What “functional folate deficiency” means

MTHFR is an enzyme that helps convert folate into the active form the body uses in methylation reactions, including recycling homocysteine to methionine.[4][3]
“Functional deficiency” here means: blood folate might look ok on a simple test, but because the enzyme works less well, the body behaves as if folate is low (e.g. higher homocysteine, impaired methylation), especially when intake is marginal.[4][3]
The common C677T and A1298C variants reduce MTHFR activity to varying degrees; in C677T homozygotes, enzyme activity can be cut by roughly half or more, which can modestly lower active folate and raise homocysteine.[4][5]

How common this is in the UK

NHS and genetics sources estimate roughly 10–12% of people in the UK and Ireland are homozygous for the C677T variant (the “TT” genotype).[1][2][6]
When you add:
- people homozygous for the other common variant (A1298C), and
- “compound heterozygotes” (one copy of each variant),
  at least around 10% and potentially a much larger fraction have a more substantially reduced‑activity enzyme, so “over a third” is a reasonable ballpark for “any significant combination.”[7][8]

Why the UK context matters

Until now, the UK has not routinely fortified white flour with folic acid, unlike the US and some other countries where background folate status is higher because of fortification.[9][10]
Legislation to add folic acid to non‑wholemeal wheat flour has been agreed and is due to be implemented by late 2026, with some products starting fortification earlier.[11][12]
In a non‑fortified setting, people with “slower” MTHFR variants are more sensitive to low dietary folate; their folate and homocysteine levels improve if total folate intake is higher.[6][3][5]

What it does not mean (important nuance)

These common MTHFR variants are polymorphisms, not rare catastrophic mutations: most people with them are well and never develop obvious disease purely because of MTHFR status.[1][4]
Professional genetics services in the UK explicitly state that MTHFR genotyping is rarely helpful for most patients, because the variants are so common and the effect size on risk for conditions like thrombosis or cardiovascular disease is small and inconsistent.[13][7]
Clinical problems tend to emerge when several factors stack:
- low folate intake or increased need (pregnancy, certain medications)
- other genetic variants
- lifestyle factors such as smoking, heavy alcohol use, or very poor diet.[6][4][3]

Practical implications of that quoted text

In plainer language, that paragraph is essentially saying:

A substantial minority of people in the UK have MTHFR variants that make them “less efficient” at using folate. [1][7][6]
Because the UK has only just moved toward fortifying flour, the consequences of those variants on folate status and homocysteine may be more noticeable here than in countries with long‑standing folic‑acid fortification.[9][10][11]
Most of these people will never know they have the variant and will be fine, but if you add other vulnerabilities (e.g. low folate diet, pregnancy, vascular risk, some drugs), it could tip someone into meaningful folate insufficiency and associated risks.[6][4][3]

If this relates to you or someone post‑stroke in your community, the main “actionable” message in mainstream guidelines is usually about ensuring good overall folate/B‑vitamin status and vascular risk management, rather than chasing MTHFR tests, unless a genetics team has a specific reason to look for rare, severe MTHFR deficiency.[1][7][14]

Citations:
[1] MTHFR associated Folate Disorders - NHS Tayside https://www.nhstayside.scot.nhs.uk/OurServicesA-Z/Genetics/PROD_375885/index.htm
[2] MTHFR - Lab Tests Online-UK https://labtestsonline.org.uk/tests/mthfr
[3] Methylenetetrahydrofolate reductase - Wikipedia https://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase
[4] Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5 … https://pmc.ncbi.nlm.nih.gov/articles/PMC7564482/
[5] MTHFR and Folic Acid “Build Up”: What You Need to Know https://www.mygenefood.com/blog/mthfr-and-folic-acid-build-up-what-you-need-to-know/
[6] MTHFR Gene - Shine - Spina Bifida & Hydrocephalus https://www.shinecharity.org.uk/spina-bifida/mthfr-gene
[7] MTHFR genetic testing/counselling - East Genomics https://www.eastgenomics.nhs.uk/for-healthcare-professionals/clinical-genetics-services/east-anglian-medical-genetics-service/referrals/referrals-not-routinely-accepted/mthfr-genetic-testingcounselling/
[8] The prevalence of homozygous MTHFR polymorphism(s) in a … https://www.ejgm.co.uk/article/the-prevalence-of-homozygous-mthfr-polymorphisms-in-a-turkish-university-hospital-population-that-7456
[9] Folic acid fortification in the UK - BDA https://www.bda.uk.com/resource/folic-acid-fortification-in-the-uk.html
[10] Folic acid: UK to fortify flour to protect against birth defects https://www.bmj.com/content/387/bmj.q2531
[11] Update: Folic Acid Fortification - Food Standards Scotlandwww.foodstandards.gov.scot › news › update-folic-acid-fortification https://www.foodstandards.gov.scot/news/update-folic-acid-fortification
[12] Flour fortification with folic acid – a landmark decision for … https://bmjgroup.com/flour-fortification-with-folic-acid-a-landmark-decision-for-public-health/
[13] Patients who are UNLIKELY to benefit from a referral … - Belfast Trust https://belfasttrust.hscni.net/service/laboratory-services/clinical-genetics/patients-who-are-unlikely-to-benefit-from-a-referral-to-clinical-genetics/
[14] Methylenetetrahydrofolate Reductase Deficiency https://metabolicsupportuk.org/condition/methylenetetrahydrofolate-reductase-deficiency/
[15] COVID‐19 spreading across world correlates with C677T allele of … https://pmc.ncbi.nlm.nih.gov/articles/PMC8209953/

It's possible relevance

What’s the relevant to life post stroke particularly with regard to fatigue

Post‑stroke, folate/B‑vitamin status and MTHFR variants mostly matter indirectly, via their effects on homocysteine, vascular health, and overall recovery; they are a possible contributor to fatigue, but not usually the main driver.[1][2][3]

Folate, homocysteine and the brain

Higher folate levels after ischaemic stroke are associated with lower mortality and disability, partly because they help keep homocysteine down.[1]
Elevated homocysteine can damage endothelium, increase oxidative stress, and impair microvascular function, which may worsen brain perfusion and recovery.[1][4]
MTHFR “slow” variants push homocysteine up when folate/B12/B6 intake is only just adequate, so any marginal deficiency is more likely to show up biochemically in those people.[5][6]

How this links to fatigue

Post‑stroke fatigue is multifactorial, but folate/B‑vitamin issues can overlap with several mechanisms:

Energy and mood: Low folate and B12 are linked to low mood, cognitive slowing and low energy in general populations; post‑stroke, that can blur into the broad “fatigue” picture.[7]
Muscle function and rehab: In one rehabilitation study, lower folate levels were associated with poorer lower‑limb recovery and functional performance, which in real life feels like “I hit a wall very quickly.”[2]
Vascular strain: If homocysteine is high, small‑vessel disease and impaired perfusion can add to cognitive fatigue and “brain fog,” especially on top of pre‑existing vascular burden.[1][4]

None of this means “MTHFR causes post‑stroke fatigue,” but it does mean that in someone with fatigue, marginal folate/B12/B6 plus a slow MTHFR genotype is one modifiable piece of the puzzle.

Where MTHFR fits in post‑stroke care

Risk and recurrence: Meta‑analyses show MTHFR variants (and resultant hyperhomocysteinaemia) modestly increase ischaemic stroke susceptibility, especially small‑vessel and lacunar patterns.[5][8][6]
Prevention strategy: Re‑analyses of trials and expert reviews argue that B‑vitamin regimens that effectively lower homocysteine (folate plus appropriate B12 form) do reduce stroke events, including recurrent stroke, even though some older trials looked “neutral.”[9][3][10]
Genetics vs practice: Because the polymorphisms are common and effect sizes are modest, guidelines tend to prioritise “measure and treat homocysteine/folate/B12 if clinically indicated” rather than testing everyone’s MTHFR.[11][3][12]

Practical implications for life after stroke

In terms of lived experience with fatigue, the relevance is mostly about ruling out avoidable drag factors:

Check basics: In someone with significant fatigue or cognitive fog post‑stroke, it is reasonable clinical practice to look at folate, B12 and sometimes homocysteine, alongside thyroid, iron, sleep, mood and medication effects.[11][7]
Optimise intake: Ensuring good dietary folate (greens, beans, fortified grains) and adequate B12/B6 is low‑risk and may support both vascular prevention and functional recovery, particularly in countries only now moving to folic‑acid fortification like the UK.[1][13][3]
Individual variation: A person with a slow MTHFR variant, borderline folate and high homocysteine may notice improvement in energy or cognition when those are corrected, but that tends to be on a case‑by‑case basis rather than a guaranteed effect.[1][2][3]

If you want, the next step can be to map this onto a simple “post‑stroke fatigue checklist” you could use in your community, with B‑vitamins/homocysteine as one line item among sleep, mood, activity pacing, meds, pain, etc.

Citations:
[1] Folate, Homocysteine, and Adverse Outcomes After … https://pmc.ncbi.nlm.nih.gov/articles/PMC11681484/
[2] Functionality of patients with post-stroke hemiplegia https://pmc.ncbi.nlm.nih.gov/articles/PMC6797917/
[3] Homocysteine Reduction for Stroke Prevention https://pmc.ncbi.nlm.nih.gov/articles/PMC10559895/
[4] Interplay between 3′-UTR polymorphisms in the … https://www.nature.com/articles/s41598-017-12668-x
[5] Homocysteine, MTHFR 677C→T polymorphism, and risk of … https://www.neurology.org/doi/10.1212/WNL.59.4.529
[6] MTHFR Polymorphisms, Homocysteine Elevation, and … https://www.neurology.org/doi/10.1212/WNL.0000000000210245
[7] Associations between homocysteine, vitamin B12, and … https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1279207/pdf
[8] MTHFR A1298C gene polymorphism on stroke risk https://pmc.ncbi.nlm.nih.gov/articles/PMC8467014/
[9] B Vitamins to Lower Homocysteine Do Prevent Stroke https://pubmed.ncbi.nlm.nih.gov/35748292/
[10] Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease | Neurology https://www.neurology.org/doi/10.1212/WNL.0b013e3182a823cc
[11] Hyperhomocysteinaemia & Stroke Risk https://www.royalbucks.co.uk/conditions-and-symptoms/hyperhomocysteinaemia/
[12] Homocysteine Reduction for Stroke Prevention | PGPM https://www.dovepress.com/homocysteine-reduction-for-stroke-prevention-regarding-the-recent-ahaa-peer-reviewed-fulltext-article-PGPM
[13] A Dose-Response Meta-Analysis of Prospective Studies https://www.sciencedirect.com/science/article/pii/S2161831322003453
[14] Lowering Homocysteine in Patients With Ischemic Stroke to … https://jamanetwork.com/journals/jama/fullarticle/198139
[15] A Notice to the Survivors: The Impact of Dietary … https://brieflands.com/journals/jkums/articles/164642

Ciao
Simon

Simon

Hedge
Susan you made it! 😁

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