Ingredient monographNo. 14 / 15

Reb M (Rebaudioside M, stevia)

What is Reb M? Rebaudioside M (Reb M) is one of the sweet compounds, called steviol glycosides, found in the leaves of the stevia plant. Steviol glycosides are 200 to 400 times sweeter than sugar.[1] Reb M sold as a sweetener is usually at least 95% pure and is made from purified leaf extract or by fermentation.[2][3]

Class
Sweetener
Form in Replenish
steviol glycosides (rebaudioside M)
Dates
Published · Last reviewed

What it is

Stevia, Stevia rebaudiana (Bertoni) Bertoni, is a plant native to parts of South America. Its leaves contain steviol glycosides, a family of molecules with the same core, steviol, carrying different numbers of sugar units.[1][4] Rebaudioside A (Reb A) and stevioside are the most familiar. Reb M is a larger molecule, with a molecular weight of 1,291.3 g/mol against 318.5 for steviol itself.[2]

Regulators have assessed at least two ways of making commercial Reb M:

  • Enzymatic conversion. Steviol glycosides purified from stevia leaves are treated with enzymes that add sugar units, converting them to Reb M. FDA has not questioned GRAS notices for Reb M made this way, including one in 2022.[3]
  • Fermentation. A genetically modified yeast, Yarrowia lipolytica, makes steviol glycosides from simple sugars; the product is purified to at least 95% steviol glycosides, mostly Reb M. EFSA found no viable cells or DNA from the production strain in the final product and no safety concern at the proposed uses.[2] In 2018 FDA did not question a GRAS notice for steviol glycosides consisting primarily of Reb M produced in Yarrowia lipolytica.[5]

Either way, the result is the same molecule. Human digestive enzymes do not break steviol glycosides apart in the upper gut. In the colon, bacteria strip the sugars off, the body absorbs the steviol, links it to glucuronic acid and excretes it in urine, with some leaving through bile.[2] Because every steviol glycoside ends up as steviol, regulators assess them as one group.[2] On the Replenish label it appears as Steviol Glycosides (Reb M), alongside erythritol and monk fruit extract.

Official reference values

Reb M is not a nutrient, so there is no RDA. The reference values are safety limits for the steviol glycoside group, expressed as steviol equivalents: the weight of steviol the glycoside contains.

Steviol glycosides, including Reb M: official reference values and regulatory status
Authority Value or status Notes
JECFA (FAO/WHO), 2008 ADI 0–4 mg per kg body weight per day, as steviol Covers steviol glycosides as a group
EFSA (EU) ADI 4 mg per kg body weight per day, as steviol equivalents A 2024 request to raise it to 6 or 16 mg was turned down
US FDA GRAS notices for high-purity Reb M answered "no questions" First notice GRN 512 (2014); later notices cover fermentation and enzymatic production
US FDA Whole-leaf and crude stevia extracts not GRAS Not permitted as sweeteners; subject to an import alert

Sources: EFSA Panel on Food Additives and Flavourings, 2023 and 2024 opinions, which also report the JECFA ADI;[2][4] FDA, Aspartame and Other Sweeteners in Food;[1] FDA GRAS Notice Inventory.[6][5][3] ADI = acceptable daily intake. GRAS = generally recognized as safe.

Replenish lists steviol glycosides (Reb M) under Other Ingredients, which carry no declared amount.

Converting the limit to Reb M itself: steviol is about a quarter of Reb M's weight (a conversion factor of 0.25), so 4 mg of steviol equivalents per kg corresponds to about 16 mg of Reb M per kg.[2] For a 70 kg adult that is roughly 1,100 mg of Reb M a day. In EFSA's 2024 exposure estimates for all permitted uses in the EU, the highest exposures were in toddlers, whose top 5% could exceed the ADI.[4]

What the evidence says

Safety data. FDA describes the safety of steviol glycosides as extensively studied, with several chronic studies and clinical studies in humans showing no adverse effects.[1] In 2024 EFSA reviewed the absorption and metabolism data again and found insufficient justification to raise the ADI, so it stays at 4 mg/kg.[4]

Blood sugar and appetite. In a randomized crossover trial in 53 adults with overweight or obesity in England and France, biscuits sweetened with Reb M or neotame were compared with sucrose-sweetened biscuits over two-week periods. Appetite ratings and gut hormones did not differ; insulin after eating was lower with Reb M, and glucose was modestly lower.[7] The reformulated biscuits also used polyols in place of sugar, so the comparison is between less-sugar and sugar biscuits, not a test of Reb M on its own. One author is employed by a sweetener producer. In a crossover study in 30 healthy men, drinks sweetened with stevia, monk fruit or aspartame caused smaller glucose and insulin spikes than a sucrose drink in the first hour. The men then ate more at lunch after the sweetener drinks, responses after lunch were higher, and total glucose and insulin over 3 hours did not differ.[8]

WHO guidance. In 2023 WHO issued a conditional recommendation that non-sugar sweeteners, which it says include stevia and stevia derivatives, not be used as a means of weight control or of reducing the risk of noncommunicable diseases.[9] The guideline is not a safety assessment, does not change JECFA's intake limits, and does not apply to people with existing diabetes.[9]

Safety and interactions

The ADI is the main safety marker.[4] FDA treats the purified ingredient and the plant differently: high-purity (95% minimum) steviol glycosides have GRAS notices FDA did not question, while stevia leaf and crude extracts are not considered GRAS and are not permitted as sweeteners.[1] "Stevia" on a label means the purified glycosides, not the leaf.

We found no labeled drug interactions for steviol glycosides in the sources we used. Lower blood sugar after a meal compared with sugar is expected when sugar is removed, and is not a reason to change diabetes medicines on your own.

If you take prescription medicine, ask your pharmacist or prescriber before adding a supplement.

In Replenish

Replenish uses steviol glycosides, as Reb M, with monk fruit extract and erythritol to sweeten a lemon-lime mix that supports hydration.† It appears under Other Ingredients, which carry no declared amount. See Replenish, how sweeteners fit into choosing a mix in the best electrolytes for a GLP-1, and the wider context in what to drink on a GLP-1 besides water.

Frequently asked questions

Is Reb M the same as stevia?

It is one of the sweet compounds in the stevia leaf. Sweeteners sold as stevia are purified steviol glycosides, which may be Reb A, Reb M or a mix; the leaf itself is not permitted as a sweetener in the US.[1][6]

Is Reb M natural or synthetic?

The molecule occurs in the stevia leaf. Commercial Reb M is made from purified leaf extract converted with enzymes, or by fermentation with a modified yeast, and then purified.[3][2]

How much Reb M is safe a day?

The ADI is 4 mg of steviol equivalents per kg of body weight, about 16 mg of Reb M per kg.[2][4] That is roughly 1,100 mg of Reb M a day for a 70 kg adult.

Does Reb M raise blood sugar?

Steviol glycosides are not broken down or absorbed in the upper gut.[1] In trials, foods and drinks sweetened with stevia gave lower glucose and insulin responses than sugar-sweetened versions, at least in the first hour.[7][8]

Does WHO say not to use stevia?

WHO's 2023 guideline suggests not using non-sugar sweeteners, including stevia, as a means of weight control or of reducing disease risk. It is conditional, is not a safety finding, and leaves intake limits unchanged.[9]

References

  1. US Food and Drug Administration. Aspartame and Other Sweeteners in Food. fda.gov. fda.gov. ↩︎
  2. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, et al. Safety evaluation of the food additive steviol glycosides, predominantly Rebaudioside M, produced by fermentation using Yarrowia lipolytica VRM. EFSA J. 2023;21(12):e8387. Full text. PMID: 38125973. doi: 10.2903/j.efsa.2023.8387. ↩︎
  3. US Food and Drug Administration. GRAS Notice No. 1010: Rebaudioside M obtained by enzymatic treatment of steviol glycosides purified from the leaves of Stevia rebaudiana (Bertoni). FDA GRAS Notice Inventory. 2022. hfpappexternal.fda.gov. ↩︎
  4. EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, et al. Scientific opinion on the extension of the authorisation of use of the food additive steviol glycosides (E 960a-d) and the modification of the acceptable daily intake (ADI) for steviol. EFSA J. 2024;22(11):e9045. Full text. PMID: 39502654. doi: 10.2903/j.efsa.2024.9045. ↩︎
  5. US Food and Drug Administration. GRAS Notice No. 759: Steviol glycosides consisting primarily of rebaudioside M produced in Yarrowia lipolytica. FDA GRAS Notice Inventory. 2018. hfpappexternal.fda.gov. ↩︎
  6. US Food and Drug Administration. GRAS Notice No. 512: High purity Rebaudioside M. FDA GRAS Notice Inventory. 2014. hfpappexternal.fda.gov. ↩︎
  7. Gibbons C, Beaulieu K, Almiron-Roig E, et al. Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium. EBioMedicine. 2024;102:105005. Full text. PMID: 38553262. doi: 10.1016/j.ebiom.2024.105005. (EU Horizon 2020 funding; one author is employed by Cargill, which sells sweeteners) ↩︎
  8. Tey SL, Salleh NB, Henry J, et al. Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. Int J Obes (Lond). 2017;41(3):450–457. PubMed. PMID: 27956737. doi: 10.1038/ijo.2016.225. (abstract read) ↩︎
  9. World Health Organization. Use of non-sugar sweeteners: WHO guideline. World Health Organization. 2023. (Recommendation and supporting information) who.int. ↩︎

General information, not medical advice. Corrections: support@zornava.com.