Short answer. Folic acid and L-5-MTHF are two different molecules, not two grades of the same one. Folic acid is fully oxidised pteroylmonoglutamic acid, CAS 59-30-3. L-5-MTHF is a reduced, methylated folate that is supplied commercially as a salt, most often the calcium salt (CAS 151533-22-1) or the glucosamine salt (CAS 1181972-37-1). For a sourcing team the decision is rarely about which material is better in the abstract. It comes down to three concrete things: what basis the assay on your quote is expressed on, whether the [6S] diastereomer is actually specified, and how much stability protection your finished format has to provide. Folic acid is the cheaper, more robust, better understood material. L-5-MTHF is the more expensive and considerably more fragile one, with a specification that has to be read line by line.
This page compares the two as raw materials on a specification sheet — identity, assay basis, stereochemistry, stability, label units and documentation. It does not compare what either form does in a person, and it does not tell you which one belongs in your product. That is a formulation and regulatory decision for your own team.
Property comparison
| Property | Folic acid | L-5-MTHF |
|---|---|---|
| Chemical identity | Pteroylmonoglutamic acid, fully oxidised synthetic folate | Reduced, methylated folate; 5-methyltetrahydrofolic acid |
| CAS (free acid) | 59-30-3 | 31690-09-2 for the (6S) form; 134-35-0 is 5-methyltetrahydrofolic acid without stereochemistry specified |
| CAS (commercial salt) | Not applicable; usually supplied as the acid | 151533-22-1 calcium salt; 1181972-37-1 glucosamine salt |
| Molecular formula | C19H19N7O6 | C20H25N7O6 free acid; C20H23CaN7O6 calcium salt; C26H38N8O11 glucosamine salt |
| Molecular weight (reported) | about 441.4 | about 459.5 free acid; about 497.5 calcium salt; about 638.6 glucosamine salt |
| Stereochemistry | No chiral centre at C6; no diastereomer question | Chiral at C6; [6S] and [6R] diastereomers exist and must be distinguished |
| Assay basis to confirm | Usually straightforward, as the acid | Salt or free-acid equivalent? The two numbers differ materially |
| Identity methods typically seen | HPLC retention plus UV or IR | HPLC plus MS, with chiral or stereospecific HPLC for the [6S] fraction |
| Oxidative stability | Comparatively robust; the oxidised form | Sensitive to oxidation; the reason protective packaging and inert headspace get specified |
| Light and moisture | Light-sensitive but manageable | Light-sensitive and hygroscopic; ambient humidity during blending is a real variable |
| Typical serving-level order of magnitude | Hundreds of micrograms | Hundreds of micrograms |
| Blend uniformity | Micro-ingredient; premix or trituration normal | Micro-ingredient; premix or trituration normal, and more sensitive to processing conditions |
| Colour | Yellow to orange-yellow | Off-white to pale yellow, varying with salt and grade |
| US label nutrient name | Declared under “Folate”, with the folic acid amount in parentheses | Declared under “Folate”; 21 CFR 101.9 names the calcium salt of L-5-MTHF as a folate component of a dietary supplement |
| Label unit | mcg DFE, with mcg folic acid in parentheses | mcg DFE; confirm the conversion factor for your form with your regulatory reviewer |
| Relative cost per unit of folate | Lower | Substantially higher |
| Overage practice | Modest, format-dependent | Commonly larger and stability-driven; get it agreed in writing before the first production run |
| Format fit | Broad, including gummies and beverages with normal precautions | Broad, but wet and high-moisture formats need stability data before commitment |
The salt-basis question, in numbers
This is the single most expensive misunderstanding on a folate quote, and it is pure arithmetic. L-5-MTHF is not sold as the free acid. It is sold as a salt, and the salt carries weight that is not folate.
Using the reported molecular weights above: the free acid is about 459.5. The calcium salt is about 497.5, so a material that is 100 percent calcium L-5-MTHF carries roughly 92.4 percent on a free-acid-equivalent basis. The glucosamine salt is about 638.6, so the same 100 percent figure corresponds to roughly 72.0 percent free-acid equivalent. Glucosamine is a heavier counter-ion than calcium, and that difference does not disappear because both certificates say 98 percent.
Put plainly: a kilogram of the calcium salt carries in the region of 1.28 times the free-acid-equivalent folate of a kilogram of the glucosamine salt. Two quotes at the same assay and the same price per kilogram are therefore not the same offer. Before comparing prices, normalise both to the same basis and ask each supplier, in writing, which basis their assay is expressed on. We supply both salts, and we would rather a buyer runs this arithmetic before ordering than after.
This is the seventh entry in a pattern this site keeps documenting: quercetin dihydrate carries water, PQQ disodium carries sodium, pterostilbene glucoside and apigenin glycosides carry sugar, TUDCA is commonly a sodium salt, polydatin carries a glucose unit, and folate salts carry calcium or glucosamine. The assay number is never the whole answer. The basis behind it is.
The [6S] question is a CAS number question
Folic acid has no chiral centre at C6, so there is no diastereomer conversation to have. Reduced folates do. 5-Methyltetrahydrofolic acid exists as [6S] and [6R] diastereomers, and only one of them is the form found in foods and in circulation.
The useful thing here is that the identifiers already encode this, and most quotes do not use them carefully. CAS 134-35-0 is 5-methyltetrahydrofolic acid with no stereochemistry specified. CAS 31690-09-2 is the (6S) form. A quote that names only 134-35-0 has not told you what you are buying. So the ask is specific, and it is a documentation ask rather than an argument:
- State the diastereomeric purity as a numeric specification, not as the phrase “L-form” in marketing text.
- State the analytical method used to determine it. A stereospecific or chiral HPLC method is what answers this; a routine achiral assay does not.
- State whether the reported assay is the total 5-MTHF content or the [6S] content specifically.
- Name the reference standard and its source.
Any supplier who can answer those four in writing is easy to work with. Any supplier who cannot has told you something useful too.
Stability is where the two materials actually diverge
Folic acid is the fully oxidised form, which is exactly why it has been the workhorse for decades: it tolerates processing. L-5-MTHF is a reduced folate, and reduced compounds are by definition easier to oxidise. In practice that shows up as sensitivity to oxygen, light, moisture and low pH, and it is why L-5-MTHF grades are routinely supplied with protective packaging instructions and why overage is a normal part of the commercial conversation rather than a sign that something is wrong.
What this means for a buyer is that a certificate of analysis describes the material on the day it was tested, and a folate decision needs the second document as well. Ask for real-time and accelerated stability data in a matrix resembling yours — a number generated on neat powder in a sealed foil bag says very little about the same material in a pectin gummy at 25 C and 60 percent relative humidity. Ask what the overage assumption is, what shelf life it supports, and what packaging and headspace that assumption depends on.
The label unit question, and why it is not a detail
US folate labelling runs in dietary folate equivalents. Under 21 CFR 101.9, folate is declared under the nutrient name “Folate” in mcg DFE, and where folic acid is added its amount is given in mcg in parentheses after the folate declaration. The same regulation explicitly names the calcium salt of L-5-MTHF as a synthetic folate component of a dietary supplement, which is why the nutrient name on the panel is “Folate” rather than the raw material name.
The arithmetic that turns milligrams of raw material into the number printed on the panel is not the same for every folate form, and FDA has published guidance specifically on converting units of measure for folate on the Nutrition and Supplement Facts labels. We are a raw material supplier, not your regulatory reviewer, so the honest position is this: we will tell you exactly what is in the drum, on which basis, with which method — and the DFE conversion that applies to your finished panel is a question to settle with your own regulatory reviewer before you set the serving size. Teams that leave this to the end usually discover it after the artwork is approved.
Choose folic acid if…
- Cost per unit of folate is a governing constraint and the format is conventional.
- The process is thermally or oxidatively demanding and you want the more forgiving material.
- Your label and marketing position does not depend on specifying a reduced folate form.
- You want the simplest possible specification conversation, with no salt basis and no diastereomer clause.
Choose L-5-MTHF if…
- Your positioning specifies a reduced, methylated folate form and your regulatory reviewer has cleared the language you intend to use.
- You are prepared to specify the salt, the basis, the diastereomeric purity and the method, and to hold suppliers to all four.
- You can support the stability requirements — packaging, headspace, moisture control and an agreed overage.
- The finished format is dry, or you have matrix stability data for a wet format in hand.
Specify the salt deliberately if…
- You are comparing quotes across suppliers, in which case normalise every one to free-acid equivalent before you look at price.
- Your fill weight or blend design is tight, since the calcium and glucosamine salts differ by roughly 28 percent in free-acid-equivalent content per unit mass.
- You have an existing formula and are considering a salt switch, which changes the raw-material weight in the batch sheet even when the declared folate stays the same.
Formulation and sourcing notes
Micro-dosing is a uniformity problem before it is anything else
Both materials dose in the hundreds of micrograms against batch sizes measured in kilograms, which is a dilution ratio where blend uniformity, not assay, decides whether the finished product meets label. Premix or trituration with a compatible carrier is standard practice for both. If you are moving from folic acid to L-5-MTHF, treat the premix as a new development item rather than a substitution, because the physical properties of the two powders are not the same.
Wet formats need matrix data, not powder data
Gummies, stick packs reconstituted into liquid, and ready-to-drink formats each expose a reduced folate to moisture, oxygen and pH conditions that a foil-bagged powder never sees. Ask for stability in a matrix resembling yours, at your intended storage condition, for at least the shelf life you intend to print. If that data does not exist yet, say so internally and plan a trial rather than assuming.
Ask which method produced the number
Folate assays are method-dependent, and the method matters more here than for most ingredients. For L-5-MTHF, ask whether the assay is HPLC with UV detection or an LC-MS method, whether the stereochemistry was determined and how, and which reference standard was used. Two laboratories can report different numbers on the same drum simply because they answered different questions.
Packaging instructions are part of the specification
For a reduced folate, packaging is not a shipping detail. Protective packaging, controlled headspace and defined storage conditions are the conditions under which the assay and stability data are valid at all. Record them on your incoming specification, and make sure your warehouse handling matches them.
Do not compare price until the basis matches
Convert every quote to the same basis: same salt or free-acid equivalent, same assay definition, same diastereomer specification. Only then divide by price. A quote that looks 20 percent cheaper on a per-kilogram basis can be the more expensive material once normalised, and the difference between the two commercial salts alone is close to 28 percent.
Decide the label unit before the serving size
The DFE arithmetic sets what the panel can say, which sets the serving size, which sets the raw-material cost per bottle. Teams that resolve the labelling question first design the formula once. Teams that leave it to the end redesign it.
Documentation to request
For either form: certificate of analysis with assay, method and reference standard named; full specification sheet; identity confirmation; heavy metals; residual solvents; microbiological profile; allergen and GMO statements; stability data with the storage condition stated; packaging and storage instructions; lot traceability.
For L-5-MTHF specifically: which salt, stated explicitly; whether the assay is expressed on the salt or on a free-acid-equivalent basis; diastereomeric purity as a number with the method that produced it; the CAS number matching the stereochemistry you are buying; the overage assumption and the shelf life it supports; the packaging and headspace conditions the stability data depends on.
For folic acid specifically: compendial grade and monograph reference where applicable; particle size distribution if your blend design depends on it; the folic acid figure your label will carry in parentheses.
If you want a general framework for reading any supplier document, our guide on how to verify a supplier certificate of analysis covers the questions that apply regardless of ingredient, and our quality and certifications page sets out what we can provide under buyer review.
What we do not claim on this page
This page compares raw material properties only. It does not state or imply that either form treats, prevents, cures or diagnoses any condition. It makes no claim about absorption, utilisation, blood levels or any physiological outcome for either material, and it makes no comparison between them on any of those grounds — published work on that subject exists, it is not our data, and we will not borrow it as a supplier claim. It makes no statement about suitability for pregnancy, prenatal use, any genotype or any specific population. It makes no statement about what folate status means for any individual. Physical constants are given as reported values and should be confirmed against batch documentation and against a current authoritative reference rather than against any web page, including this one. Regulatory positioning, label claims and finished-product substantiation are the responsibility of the brand and its regulatory reviewer.
Related guides and product routes
- L-5-Methyltetrahydrofolate — our product route, supplied as the calcium and glucosamine salts.
- Women’s health ingredients: a formulator’s selection guide — the category pillar this comparison sits under.
- How to verify a supplier certificate of analysis.
- How to qualify a nutraceutical ingredient supplier.
- All ingredient selection guides, or browse the full ingredient catalog.
Frequently asked questions
Is L-5-MTHF the same thing as folic acid?
No. They are different chemical entities. Folic acid is fully oxidised pteroylmonoglutamic acid, CAS 59-30-3, with molecular formula C19H19N7O6 and a reported molecular weight of about 441.4. L-5-MTHF is a reduced, methylated folate, formula C20H25N7O6 as the free acid with a reported molecular weight of about 459.5, supplied commercially as the calcium or glucosamine salt. Because they are different molecules with different weights, salt forms and stability profiles, a substitution is a reformulation and should be planned as one.
What does the CAS number on a 5-MTHF quote actually tell me?
More than most buyers use it for. CAS 134-35-0 refers to 5-methyltetrahydrofolic acid without specifying stereochemistry, while CAS 31690-09-2 refers to the (6S) form. The commercial salts have their own numbers: 151533-22-1 for the calcium salt and 1181972-37-1 for the glucosamine salt. If a quote names only the unspecified number, ask which diastereomer is being supplied, at what numeric purity, and by which analytical method.
Calcium salt or glucosamine salt — which should we specify?
That depends on your formula and your commercial comparison, not on a general ranking. The practical difference a buyer must account for is weight: the calcium salt has a reported molecular weight of about 497.5 against about 638.6 for the glucosamine salt, so per unit mass the calcium salt carries roughly 1.28 times the free-acid-equivalent folate. Specify the salt explicitly on the purchase specification, keep the basis consistent across quotes, and re-check the batch sheet if you switch, because the raw-material weight changes even when the declared folate does not.
Why do two 5-MTHF quotes at the same assay give different folate per kilogram?
Almost always because the assays are expressed on different bases. A percentage stated on the salt and a percentage stated as free-acid equivalent are different numbers describing the same drum, and the gap is larger for the glucosamine salt than for the calcium salt. Ask every supplier to state the basis in writing, normalise all quotes to one basis, and only then compare price. The same trap appears with hydrated, salt and glycoside forms of many other ingredients.
What stability data should we ask for before a gummy or stick-pack trial?
Ask for data in a matrix resembling yours, at your intended storage condition, covering at least the shelf life you plan to print, together with the packaging and headspace conditions the data assumes and the overage assumption built into it. Powder-in-foil data is useful for storage and handling but does not predict behaviour in a high-moisture matrix. Where matrix data does not yet exist, plan a stability trial rather than infer from the powder result.
What documents do you provide, and can we get a sample?
Certificate of analysis, specification sheet, method and reference standard information, heavy metals, residual solvents, microbiological profile, allergen and GMO statements, stability data and packaging and storage instructions. Certificates are available under buyer review. Send your target format, serving size, market channel and the salt and basis you intend to specify, and we will respond with the matching documentation and a sample.
Request a sample, COA or specification
Tell us the format you are building, the serving size you have in mind, and which folate form and basis your specification calls for. We will send the matching documentation and a sample for review.
Nutrition BioTech
1601 W. Mission Blvd, Suite 103 (DL#29), Pomona, CA 91766
(909) 745-1357 · [email protected]
Request a sample, COA or specification