Methylfolate (5-MTHF) vs L-Citrulline
Vitamin vs Amino Acid · evidence-backed comparison
- • Methylfolate (5-MTHF) has the stronger evidence base (strong (multiple rcts / meta-analyses)).
- • L-Citrulline has the broader effect profile across the 9 effect categories.
- • Methylfolate (5-MTHF) is cheaper per serving ($0.22 vs $0.65).
- • L-Citrulline has a slightly cleaner safety profile.
Side-by-side traits
| Trait | Methylfolate (5-MTHF) | L-Citrulline |
|---|---|---|
Category | Vitamin | Amino Acid |
Active compound | L-5-methyltetrahydrofolate | L-citrulline (or citrulline malate 2:1) |
Form available | Capsule, Tablet | Powder, Capsule |
Source | synthetic | microbial |
Typical dose | 400–1000 mcg daily | 6–8 g pre-workout (citrulline malate 8 g) |
Dose range | 400–1000 mcg | 6–8 g |
Loading protocol | — | — |
Best taken with | with food | water, empty stomach |
Best time of day | morning | pre-workout |
Bioavailability How efficiently the body absorbs and utilizes the compound. | Very High (5/5) | Very High (5/5) |
Onset time | Cumulative: 4–8 weeks | Acute: 60 min |
Half-life | ~3 hours | ~1 hour |
Evidence level Quality and quantity of human research. | Strong (multiple RCTs / meta-analyses) | Moderate (some RCTs) |
Overall effect Subjective effect magnitude. | Low (2/5) | Moderate (3/5) |
Muscle / strength | Very Low (1/5) | Moderate (3/5) |
Physical energy | Moderate (3/5) | High (4/5) |
Focus / cognition | Moderate (3/5) | Low (2/5) |
Mood / stress | High (4/5) | Low (2/5) |
Sleep quality | Very Low (1/5) | Very Low (1/5) |
Immunity | Low (2/5) | Very Low (1/5) |
Recovery Post-exercise recovery support. | Very Low (1/5) | Moderate (3/5) |
Longevity / healthspan | Moderate (3/5) | Low (2/5) |
Safety rating 5 = exceptionally well-tolerated; 1 = significant risk profile. | High (4/5) | Very High (5/5) |
Price per serving Approximate USD per typical daily dose. | $0.22 | $0.65 |
Vegan friendly | Yes | Yes |
Gluten free | Yes | Yes |
3rd-party tested | Yes | Yes |
About Methylfolate (5-MTHF)
Pre-methylated folate that bypasses MTHFR variants. Essential during pregnancy and for treatment-resistant depression with low folate.
About L-Citrulline
Pre-workout staple for vasodilation and reduced muscle soreness. Raises plasma arginine more efficiently than arginine itself.
Vetted brands, third-party testing, ships worldwide.
Vetted brands, third-party testing, ships worldwide.
Methylfolate (5-MTHF) safety
Common side effects:
- • Anxiety / irritability (over-methylation)
- • Insomnia (PM use)
Avoid if:
- • Bipolar disorder
Drug interactions:
- • Methotrexate
- • Antiseizure meds
L-Citrulline safety
Common side effects:
- • Generally none
Avoid if:
- • Severe hypotension
- • Sildenafil interactions
Drug interactions:
- • Sildenafil
- • Blood pressure meds
Common uses
- • Pregnancy
- • MTHFR variants
- • Depression
- • Homocysteine
Stacks well with: Vitamin B12 (Methylcobalamin), Betaine Anhydrous
Common uses
- • Pre-workout pump
- • Endurance
- • Reduced DOMS
Stacks well with: Beta-Alanine, Creatine Monohydrate, Caffeine
Related comparisons
Medical disclaimer
SupplementDuel is for educational purposes only and is not medical advice. Consult a physician before starting, stopping, or combining supplements — especially if you are pregnant, breastfeeding, take prescription medication, or have a chronic condition.