Methyl Folate (5-Methyltetrahydrofolate)
Methyl folate (5-methyltetrahydrofolate, 5-MTHF) is the biologically active form of vitamin B9 (folate). It is the molecule the body actually uses — folic acid (the synthetic form added to flour and most cheap supplements) must first be converted by the MTHFR enzyme to 5-MTHF before it can do anything. Roughly 40 % of the UK population carries one or two copies of an MTHFR gene variant that reduces this conversion. Methyl folate skips the conversion step altogether. Quatrefolic® and Metafolin® are the two trademarked research-grade preparations.
Camden Medicals editorial · Last reviewed 12 June 2026 · Next review June 2027
- Cross-checked against
- NHS
- NICE
- BNF
- EFSA
- FSA
Camden's editorial team independently graded each health claim below on the strength of the published evidence — see the grade beside every condition.
- Class
- Vitamin
- Typical daily dose
- UK NRV is 200 µg/day. NHS pregnancy guidance is 400 µg/day. Common supplement doses range 200–1000 µg/day. Methotrexate-related supplementation is 5 mg/week on prescription. Depression-adjunct trials have used 7.5–15 mg/day of L-methylfolate (above the OTC food-supplement range).
- Top use evidence
- Strong
On this page
What it is
Folate is the umbrella term for vitamin B9 in all its naturally occurring forms — the polyglutamate folates found in dark-green vegetables, pulses, liver, and citrus fruits. Folic acid is the fully oxidised, monoglutamate, synthetic form used in fortified flour and most cheap supplements; it is stable but not active. To work, folic acid must be enzymatically reduced (by dihydrofolate reductase) and then methylated (by methylenetetrahydrofolate reductase, MTHFR) into 5-methyltetrahydrofolate — 5-MTHF — the form that actually circulates in plasma and crosses the blood-brain barrier.
The MTHFR gene has two well-studied variants — C677T and A1298C. Heterozygotes (one copy) have ~30-40 % reduced enzyme activity; homozygotes (two copies of C677T) have ~70 % reduced activity. Across UK populations, roughly 30-40 % carry at least one variant. These individuals convert folic acid less efficiently and tend to have higher plasma homocysteine when relying on synthetic folic acid. Direct supplementation with 5-MTHF — methyl folate — bypasses the MTHFR step entirely, delivering the active folate the body would otherwise have to manufacture.
Quatrefolic® (a glucosamine salt of (6S)-5-MTHF, manufactured by Gnosis by Lesaffre) and Metafolin® (a calcium salt of (6S)-5-MTHF, manufactured by Merck KGaA) are the two main research-grade preparations, each cited in UK and EU regulatory submissions. The (6S) designation is the natural enantiomer; racemic (6R,S)-5-MTHF is older, less used, and less stable. A label that only says "methylfolate" without naming a salt or the (6S) form is less informative than one that does.
At a glance
- Methyl folate (5-MTHF) is the active form of vitamin B9 — what the body uses, not what it has to convert.
- Folic acid → 5-MTHF requires the MTHFR enzyme; about 40 % of people have a variant that slows this. Methyl folate bypasses the bottleneck.
- UK adult NRV = 200 µg/day. Pregnancy: NHS recommends 400 µg/day folic acid before and during the first 12 weeks of pregnancy to reduce neural-tube-defect risk.
- Authorised UK health claims include "contributes to normal blood formation", "to normal homocysteine metabolism", "to maternal tissue growth in pregnancy", "to the reduction of tiredness and fatigue", among others — at ≥15 % NRV (≥30 µg).
What people use it for
Women planning pregnancy or in the first 12 weeks of pregnancy
400 µg folic acid (or 5-MTHF) daily reduces the risk of neural tube defects in the developing baby. NHS guidance is universal — every woman trying to conceive should be supplementing. Higher doses (5 mg) are prescribed by a GP for women with diabetes, on anti-epileptic medication, with a previously affected pregnancy, or with BMI > 30. [7,1]
Some evidenceStrongAdults with diagnosed MTHFR variants or elevated homocysteine
Direct 5-MTHF supplementation bypasses the conversion bottleneck. Trials show 5-MTHF lowers plasma homocysteine at least as effectively as folic acid in MTHFR-variant carriers; tolerability is similar. [8,9]
Some evidenceModerateAdults wanting "folate for tiredness / immune / psychological function" without the conversion step
At ≥15 % NRV (30 µg) the GB NHC register authorises a set of folate health claims that apply equally to folic acid and to 5-MTHF: contribution to reduction of tiredness and fatigue, normal psychological function, normal immune function, normal blood formation, normal amino acid synthesis, normal homocysteine metabolism, and a role in cell division. 5-MTHF carries no extra claim entitlement; it is a vehicle choice. [2]
Popular, not provenInsufficientAdults on methotrexate, phenytoin, sulfasalazine, or trimethoprim
These medicines deplete folate or interfere with folate metabolism; folate supplementation is sometimes co-prescribed under medical supervision. Do not start unsupervised — methotrexate dosing in particular is timed against folate. Talk to your prescriber. [6]
Some evidenceModerate
How it works
5-MTHF is a one-carbon donor in the methylation cycle: it transfers its methyl group to homocysteine (forming methionine, regenerating SAMe — S-adenosylmethionine — the universal methyl donor) and is itself recycled. SAMe-dependent methylation reactions feed DNA synthesis (purines and thymidine), neurotransmitter synthesis (serotonin, dopamine, noradrenaline), phospholipid metabolism, and gene-regulatory methylation. Inadequate folate → impaired DNA synthesis (megaloblastic anaemia in deficiency) and elevated homocysteine (a vascular risk marker). The neural-tube-defect protection observed at periconceptional folic-acid intake reflects this DNA-synthesis role during early embryonic neurulation.
Common myths
Myth"Folic acid is the same as folate / methyl folate — they're interchangeable."
RealityThey share an authorised-claim wording but they are not the same molecule. Folic acid is synthetic and inactive until converted; 5-MTHF is the active form. For most people with normal MTHFR function, both work. For the ~40 % of the population with MTHFR variants, 5-MTHF is the more efficient vehicle. [8]
Myth"High-dose folate "improves brain function" or "treats depression"."
RealityAt deficiency, repleting folate corrects deficiency-related symptoms (including fatigue and psychological symptoms — both are authorised health-claim wordings for folate at ≥15 % NRV). At sufficiency, taking more does not give more. UK supplement marketing must use the authorised wording, not "boost" or "treat" language. [2]
Myth""Natural" folate from food is unsafe at high doses, so synthetic folic acid is safer."
RealityReverse. Dietary folate has no documented upper limit. The UK SACN tolerable upper intake is set on synthetic folic acid (1 mg/day from supplements + fortified foods) because high circulating unmetabolised folic acid is the specific concern in non-converters. 5-MTHF avoids the unmetabolised-folic-acid issue.
Common online questions
Synthesised from the questions UK shoppers most often ask online about Methyl Folate (5-Methyltetrahydrofolate). Each answer is editorial and links to its evidence in the Sources list below.
How is methyl folate different from the folic acid in a regular multivitamin?
Folic acid (the kind in cheap multivitamins and fortified bread) is synthetic and not biologically active until two enzymatic conversions have happened — the second of which (MTHFR) is impaired in roughly 40 % of people. Methyl folate (5-MTHF) is the active form already; the body uses it directly. For people with MTHFR variants, methyl folate is the more efficient form. For people with normal MTHFR function, both forms reach the same plasma 5-MTHF endpoint at typical doses. [8]
Should I take methyl folate if I'm planning a pregnancy?
The NHS recommends 400 µg daily of folic acid (or 5-MTHF) starting before conception and continuing through the first 12 weeks of pregnancy. Methyl folate counts. If you have a previous pregnancy affected by neural tube defects, diabetes, antiepileptic medication, or BMI > 30, your GP may prescribe 5 mg/day — get this on prescription, not self-treated. Talk to your midwife about which form to use. [1]
Can I take methyl folate if I'm on methotrexate?
Talk to your prescriber. Methotrexate is a folate antagonist — its therapeutic effect partly depends on folate antagonism, and rheumatologists often co-prescribe folic acid 5 mg weekly on non-methotrexate days to limit side effects. Adding extra folate unsupervised may interfere with methotrexate dosing for cancer indications. Always check with the team that prescribed your methotrexate. [6]
Quatrefolic® vs Metafolin® — which is better?
Both are research-grade (6S)-5-MTHF preparations, each backed by regulatory submissions and clinical data. Quatrefolic® is the glucosamine salt; Metafolin® is the calcium salt. Quatrefolic® has documented better stability and water solubility under manufacturing conditions; Metafolin® has the longer regulatory track record. For a finished consumer product, both are acceptable choices. A label that names neither and just says "5-MTHF" or "L-methylfolate" is less informative.
⚖️ The official position
What may lawfully be claimed about Methyl Folate (5-Methyltetrahydrofolate) in Great Britain. This is a regulatory position, not an evidence grade.
A health claim is authorised in Great Britain.
“Folate contributes to maternal tissue growth during pregnancy”
“Folate contributes to normal amino acid synthesis”
“Folate contributes to normal blood formation”
“Folate contributes to normal homocysteine metabolism”
“Folate contributes to normal psychological function”
“Folate contributes to the normal function of the immune system”
“Folate contributes to the reduction of tiredness and fatigue”
“Folate has a role in the process of cell division”
This claim is authorised for use in Great Britain under the GB Nutrition and Health Claims regulation. A product may carry it when it provides at least 15% of the UK NRV per recommended daily portion.
Authorised UK health claims
Verbatim from the GB Nutrition and Health Claims Register (Reg 432/2012 as assimilated in GB). A product can carry these claims when it provides at least 15% of the UK NRV per recommended daily portion.
8 authorised claims — show / hide
- "Folate contributes to maternal tissue growth during pregnancy"
- "Folate contributes to normal amino acid synthesis"
- "Folate contributes to normal blood formation"
- "Folate contributes to normal homocysteine metabolism"
- "Folate contributes to normal psychological function"
- "Folate contributes to the normal function of the immune system"
- "Folate contributes to the reduction of tiredness and fatigue"
- "Folate has a role in the process of cell division"
🔬 Camden’s evidence review
The research Camden reviewed, graded on its strength. This is our own appraisal — it sits beneath the official guidance above, never above it.
Neural tube defect prevention (periconceptional supplementation)
StrongEvidencestrongThe MRC Vitamin Study (Lancet 1991) established a ~70 % reduction in NTD recurrence with periconceptional folic acid 4 mg/day. Subsequent population-level evidence (Cochrane CD007950 and many cohort studies) supports 400 µg daily for first-occurrence prevention. UK NHS, RCOG, NICE all align: 400 µg pre-conception through to 12 weeks pregnancy as standard, 5 mg for higher-risk groups. 5-MTHF is an acceptable alternative form; some guidelines still default to folic acid because the regulatory-data file is older. Talk to your midwife or GP about which to use. [4]
Megaloblastic anaemia (folate deficiency)
StrongEvidencestrongFolate deficiency causes a macrocytic anaemia indistinguishable on blood film from B12 deficiency. UK guidance (BNF, NICE CKS Anaemia) is folic acid 5 mg/day for treatment, with B12 status ruled out first to avoid masking subacute combined degeneration of the cord. [3]
Homocysteine reduction
ModerateEvidencemoderateBoth folic acid and 5-MTHF reduce plasma homocysteine in deficiency states; 5-MTHF is at least equivalent in MTHFR-variant carriers. Whether homocysteine reduction translates to clinical cardiovascular event reduction has been mixed across large trials (HOPE-2, NORVIT, VISP, SU.FOL.OM3) — homocysteine drops but stroke / MI outcomes have not consistently improved at the population level. [9,10,11]
Depression as adjunctive therapy
LimitedEvidencelimitedSome trials (notably with L-methylfolate at 7.5–15 mg) suggest adjunctive benefit alongside SSRIs in folate-low patients; evidence is heterogeneous and use should be a clinician decision, not self-treatment.
Safety
Folate / methyl folate at typical food-supplement doses is well-tolerated. The UK SACN upper intake from supplements + fortified food is 1 mg/day. High-dose folate can mask B12 deficiency on a blood film — if you suspect anaemia, get blood tests rather than self-treating with high-dose folate.
Talk to your pharmacist or GP first if you:
- You take methotrexate, phenytoin, carbamazepine, sulfasalazine, or trimethoprim — folate interacts with these medicines and dosing should be supervised.
- You are pregnant or trying to conceive and have a previous NTD-affected pregnancy, diabetes, are on antiepileptics, or have BMI > 30 — you may need 5 mg/day on prescription rather than 400 µg OTC.
- You have undiagnosed anaemia symptoms — get B12 + folate blood tests first, before high-dose folate.
- You have a known yeast allergy and are taking high-dose 5-MTHF derived from yeast fermentation (rare allergy concern).
Common side effects: Generally very well tolerated. Mild GI symptoms uncommon. Sleep disruption, irritability, or headache reported by a small subset of MTHFR-variant carriers initiating 5-MTHF — usually resolves with dose adjustment.
Pregnancy and breastfeeding
400 µg/day is recommended by the NHS pre-conception and through the first 12 weeks of pregnancy (5 mg/day on prescription for higher-risk pregnancies). Folate is one of the few supplements with positive NHS recommendation in pregnancy.
Lactation NRV is moderately raised; supplemental folate at NRV is appropriate.
Talk to your GP, midwife, or pharmacist before starting any supplement during pregnancy or breastfeeding.
More clinical detail (for clinicians and informed readers)
Contraindications
- Untreated cobalamin (B12) deficiency — high-dose folate corrects the anaemia but not the neurological B12 lesion. Get blood tests first.
Drug interactions
- Methotrexate — folate antagonist; co-administration is supervised by prescriber. Do NOT self-supplement above food levels without checking.
- Phenytoin, carbamazepine, valproate — antiepileptics interact with folate metabolism in both directions; supervised supplementation only.
- Sulfasalazine — reduces folate absorption; folate co-supplementation is sometimes recommended.
- Trimethoprim, pyrimethamine — folate-pathway antagonists; high-dose folate may reduce efficacy.
- 5-fluorouracil (chemotherapy) — folate may potentiate efficacy and toxicity; specialist supervision only.
This is not an exhaustive list. Always tell your prescriber and pharmacist about every supplement you take.
Common side effects
- Generally well-tolerated; no common side-effect profile at typical food-supplement doses.
Rare side effects
- Sleep disruption, irritability, or jitteriness in some 5-MTHF starters — believed related to over-methylation; usually settles with lower starting dose.
- Allergic reactions — rare.
How to take it
- Typical supplemental range
- UK NRV is 200 µg/day. NHS pregnancy guidance is 400 µg/day. Common supplement doses range 200–1000 µg/day. Methotrexate-related supplementation is 5 mg/week on prescription. Depression-adjunct trials have used 7.5–15 mg/day of L-methylfolate (above the OTC food-supplement range).
- Timing
- No specific timing requirement.
How to spot quality
Look for
- Active form named: "5-Methyltetrahydrofolate" or "5-MTHF" — not just "folic acid".
- Salt named: glucosamine salt (Quatrefolic®) or calcium salt (Metafolin®) — these are the regulatory-grade preparations.
- (6S) designation, not racemic (6R,S).
- NRV percentage clearly declared on the label.
- GMP-certified manufacture; ideally a stability declaration (5-MTHF is moisture-sensitive).
Red flags
- Generic "Vitamin B9" with no form named.
- Folic acid presented as equivalent to 5-MTHF when it is not for MTHFR-variant carriers.
- "MTHFR cure" / "methylation reset" marketing — neither concept is a regulated health claim.
- Dose > 1 mg/day OTC (above the UK SACN upper intake).
Where Camden lands · meets the bar
Camden Medicals is evaluating a Quatrefolic® 600 µg 90-capsule product for Phase-3 launch. The candidate spec sheet names the (6S)-5-MTHF glucosamine salt (Quatrefolic®) explicitly, delivers 600 µg per capsule (300 % NRV), and is licensed through Gnosis S.p.A — a Quatrefolic® brand-use agreement would be needed to print the Quatrefolic® mark on the finished label. This product clears every encyclopaedia look-for marker. Open action: confirm Quatrefolic® licence pass-through with the supplier; confirm batch stability declaration.
Commonly combined with
Other ingredients that share a biological pathway, cofactor relationship, or evidence-backed protocol with this one. Mechanisms below cite primary physiology — not folk pairing. Doses are literature ranges, not recommendations. Talk to your pharmacist or GP before changing your stack, especially if you take prescription medication.
Vitamin B6
Moderate evidenceFolate, B12 and B6 form the homocysteine-clearance triad; folate without B12 + B6 only addresses part of the cycle.
Methyl-folate (5-methyltetrahydrofolate) donates a methyl group to homocysteine (via methionine synthase, B12-dependent) to regenerate methionine. Vitamin B6 in its active form pyridoxal-5-phosphate is the cofactor for the alternative transsulfuration route (cystathionine beta-synthase) that diverts homocysteine to cysteine and glutathione. Folate alone reduces homocysteine substantially when folate status is the limiting factor; addition of B6 widens the clearance pipeline and targets residual elevation in adequately-folated individuals.
Evidence: The HOPE-2, NORVIT and VISP trials (Lonn 2006; Bonaa 2006; Toole 2004) all combined folic acid with B6 and B12; folic-acid-only arms in NORVIT and VISP showed homocysteine drops similar to the combined-vitamin arm, with no incremental cardiovascular benefit from adding B6. The case for combining B6 with folate rests on completeness of the cycle rather than on outcome trials demonstrating B6-attributable benefit beyond folate alone. [12,13,14]
Doses studied: 200-400 ug methyl-folate + 1.4 mg B6 covers UK adult intake; trial doses ran higher (0.4-2.5 mg folic acid + 25-50 mg B6).
Vitamin B12
Strong evidenceFolate is the methyl donor and B12 is the cofactor in the same enzyme reaction; supplementing one without the other is rarely correct.
Methionine synthase requires methylcobalamin (B12) to transfer the methyl group from 5-methyltetrahydrofolate (the active folate) onto homocysteine, regenerating methionine and releasing tetrahydrofolate for further one-carbon transfers. Without adequate B12, folate becomes trapped as 5-methylTHF (the 'folate trap'), unable to participate in DNA synthesis. Clinically, folate supplementation can correct the macrocytic anaemia of B12 deficiency by bypassing the folate-trap red-cell effect, while leaving the underlying B12 deficiency to progress to subacute combined degeneration of the spinal cord. UK guidance is to confirm adequate B12 status before high-dose folate supplementation in adults.
Evidence: The biochemistry of the folate-B12 interaction is textbook (the 'methyl-folate trap'). The clinical phenomenon of folate-masking-B12 was the basis for fortification debates in the US/UK in the 1990s-2000s and remains the rationale for B12 status checks before initiating high-dose folate, particularly in older adults and in vegans/vegetarians (Pawlak 2014). [15,12]
Doses studied: 200-400 ug methyl-folate + 2.5 ug B12 (UK adult RNI). High-dose folate (>1 mg) should follow B12 status check.
Choline
Limited evidenceThe canonical one-carbon methylation pairing — folate and choline cooperate on homocysteine remethylation via parallel methyl-donor pathways.
Folate (via 5-methyl-THF and methionine synthase) and choline (via betaine and BHMT) provide methyl groups to homocysteine, regenerating methionine. The two pathways are parallel and partially compensatory: low folate increases reliance on the betaine pathway, and low choline increases reliance on the folate pathway. Homocysteine elevation can occur when both are insufficient simultaneously.
In pregnancy, both nutrients are critical — folate for neural tube closure (weeks 4-6), choline for foetal hippocampal development and cognitive markers in the offspring. UK NHS pregnancy supplement guidance requires 400 µg/day folate (preconception through first trimester); choline is increasingly being added to specialist preconception practice at 200-450 mg/day.
The combination is mechanism-additive on the homocysteine axis and complementary on the foetal neurodevelopment axis. UK Article 13.1 authorised homocysteine-metabolism claims for both.
Evidence: One-carbon methylation pathway is well-characterised. UK NHS pregnancy folate evidence is strong. Choline in pregnancy (Caudill 2018 RCT) is moderate.
Doses studied: 400 µg/day folate (or methyl-folate for MTHFR-variant individuals) + 200-450 mg/day choline (often as phosphatidylcholine) in preconception and pregnancy bundles.
Inositol (Myo-Inositol, D-Chiro-Inositol)
Moderate evidenceThe classic preconception combination — Inofolic Plus and similar UK-marketed preconception supplements pair myo-inositol with folate / methyl-folate.
Folate (400 µg/day) is the UK NHS preconception and pregnancy NTD-prevention recommendation — neural tube closure occurs by week 4-6 of pregnancy, often before pregnancy is recognised, so preconception supplementation is critical. Methyl-folate (L-5-MTHF) is the activated form preferred for women with documented MTHFR variants.
Myo-inositol contributes to PCOS-related insulin sensitisation and ovulation support. The two mechanisms are independent (folate on neural-tube methylation; inositol on insulin signalling) but the supplement is bundled because preconception is the right life stage to attend to both.
Inofolic Plus (Lo.Li. Pharma) is the most-recognised UK product combining the two; multiple UK pregnancy / PCOS multivitamins also include both. UK NICE preconception care includes folate as the principal recommendation; inositol is a non-licensed adjunct increasingly included in PCOS specialist practice.
Evidence: Folate UK NHS preconception evidence is strong. Inositol-PCOS Cochrane evidence is limited. Combined Inofolic Plus trial evidence in subfertility populations is supportive. [16]
Doses studied: 2 g + 50 mg myo-inositol : D-chiro-inositol (40:1 ratio) twice daily PLUS 400 µg/day folic acid or L-5-MTHF (methyl-folate). Inofolic Plus delivers this combination in a single sachet / product.
Iodine (I)
Strong evidencePreconception supplement bundle — iodine alongside folate, vitamin D, and iron is the UK pregnancy supplement profile.
The UK preconception supplement bundle is grounded in three distinct mechanisms each addressing a separate pregnancy outcome: folate (400 µg/day) for neural tube defect prevention (closure occurs by week 4-6, often before pregnancy is recognised); vitamin D3 (10 µg/day) for foetal calcium homeostasis and bone development; iodine (150 µg/day, total intake target 200 µg/day) for foetal neurological development via maternal-foetal thyroid hormone transfer. Iron is added where dietary intake is low or anaemia is present.
None of these acts on the others mechanistically — each addresses a separate developmental axis. The pairing is bundled because pregnancy planning is the right life stage to attend to all three simultaneously; supplements that include all three (UK pregnancy multivitamins) match the bundle.
Evidence: RCOG Green-top 23 / NHS pregnancy supplement guidance / British Thyroid Foundation pregnancy iodine guidance all support the bundle. [1]
Doses studied: Pregnancy multivitamin: 400 µg/day folate (or methyl-folate for MTHFR-variant women) + 10 µg/day vitamin D3 + 150 µg/day potassium iodide. Some include 14 µg/day iron, particularly for women with confirmed iron-deficiency anaemia.
Isotretinoin (13-cis-retinoic acid; UK POM — Roaccutane, Reticutan)
Strong evidencePost-treatment preconception planning — women of childbearing potential ending isotretinoin who plan pregnancy need preconception folate. Direct combination is NOT during-treatment but post-treatment planning.
After completing isotretinoin course, MHRA PPP recommends 1 month wash-out before contraception cessation; preconception folate (400 µg/day, methyl-folate for MTHFR-variant individuals) supports neural-tube-defect prevention from preconception through 12 weeks gestation.
Evidence: UK NHS preconception folate evidence is strong; isotretinoin sequencing follows MHRA PPP wash-out. [1,17]
Doses studied: Post-isotretinoin: 1 month wash-out → preconception folate 400 µg/day → planned conception per UK NHS pathway.
St John's Wort (Hypericum perforatum)
Limited evidenceSometimes co-formulated in "natural mood" supplements because folate status modulates monoaminergic function. Mechanism plausibility is moderate; trial evidence on the combination is limited.
Folate (and its activated form L-5-MTHF) is a methyl-group donor in the synthesis of serotonin, dopamine, and noradrenaline via the BH4 (tetrahydrobiopterin) cofactor cycle. People with folate deficiency or with the MTHFR C677T polymorphism have lower CSF folate and altered monoamine metabolism, and folate supplementation has been studied as an adjunct to SSRI antidepressants.
St John's Wort acts on the same monoamine system through serotonin/noradrenaline/dopamine reuptake inhibition. Combining the two is mechanistically coherent — folate provides the substrate, St John's Wort modulates the reuptake.
Trial evidence specific to the combination is limited; the strongest folate-as-mood-adjunct trials (Papakostas 2012 L-methylfolate + SSRI in treatment-resistant depression) used SSRIs, not St John's Wort. The combination appears in commercial supplements but is not a UK-recognised pathway. Folate supplementation alone is not associated with St John's Wort's drug-interaction profile.
Evidence: Folate-as-mood-adjunct evidence is concentrated on SSRI co-prescription (Papakostas 2012, Am J Psychiatry). Direct combination trials with St John's Wort are not published. UK NICE NG222 does not include either in the depression pathway. [18]
Doses studied: 300-1800 mg/day standardised St John's Wort extract with 400-800 µg/day folate (or 400-1000 µg L-5-MTHF for MTHFR-variant individuals). Not a Camden recommendation — trial evidence is limited and the SJW drug-interaction profile is unchanged by the combination.