SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of December 29, 2021 (86 FR 74018), we announced that we filed a food additive petition (FAP 1A4829) submitted by Lallemand Inc. (Lallemand), 1620 rue Préfontaine, Montreal, Quebec, H1W 2N8, Canada. The petition proposed that FDA amend the food additive regulations in 21 CFR part 172 to provide for the safe use of vitamin D₂ inactive bakers yeast, produced by exposing bakers yeast ( Saccharomyces cerevisiae ) to ultraviolet (UV) light and then using heat to inactivate the bakers yeast, as a nutrient supplement in foods. The proposed use would allow for the safe use of vitamin D₂ inactive bakers yeast as a source of vitamin D₂ in the same foods and at the same use levels, on a D₂ basis, for which D₂ mushroom powder is currently authorized under § 172.382.

Vitamin D is essential for human health. Vitamin D comprises a group of fat-soluble seco-sterols and occurs in many forms. The two major physiologically relevant forms are vitamin D₂ and vitamin D₃ . Vitamin D without a subscript represents vitamin D₂, vitamin D₃, or both. The major function of vitamin D is the maintenance of blood serum concentrations of calcium and phosphorus by enhancing the absorption of these minerals in the small intestine. Vitamin D deficiency can lead to abnormalities in calcium and bone metabolism, such as rickets in children or osteomalacia in adults. At high levels in the diet, vitamin D may be toxic. Excessive intake of vitamin D elevates blood plasma calcium levels (hypercalcemia) by increased intestinal absorption or mobilization from the bone that can lead to vascular and tissue calcification, with subsequent damage to the heart, blood vessels, and kidneys (Refs. 1 and 2).

To ensure that vitamin D is not added to the U.S. food supply at levels that could raise safety concerns, FDA affirmed vitamin D as generally recognized as safe (GRAS) with specific limitations as listed in 21 CFR 184.1950. Under § 184.1(b)(2), an ingredient affirmed as GRAS with specific limitations may be used in food only within such limitations, including the category of food, functional use of the ingredient, and level of use. Any addition of vitamin D to food beyond those limitations set out in § 184.1950 requires a food additive regulation. Vitamin D is affirmed as GRAS for use in certain foods as a nutrient supplement (as defined under 21 CFR 170.3(o)(20)) under § 184.1950(c)(1), in accordance with § 184.1(b)(2), as the sole source of added vitamin D only within the following specific limitations:

Vitamin D is also affirmed as GRAS under § 184.1950(c)(2) and (3) for use in infant formula and margarine, respectively. Vitamin D₂ is an approved food additive under § 172.379 for use as a nutrient supplement in edible plant-based beverages intended as milk alternatives, edible plant-based yogurt alternatives, soy beverage products, soy-based butter substitute spreads, and soy-based cheese substitutes and soy-based cheese substitute products. Vitamin D₃ is an approved food additive under § 172.380 for use as a nutrient supplement in certain calcium-fortified 100 percent fruit juices and fruit juice drinks; meal replacement and other-type bars that are represented for special dietary use in reducing or maintaining body weight; soy-protein based meal replacement beverages that are represented for special dietary use in reducing or maintaining body weight; certain cheese and cheese products; certain meal replacement beverages that are not intended for special dietary use in reducing or maintaining body weight; foods represented for use as a sole source of nutrition for enteral feeding; milk that contains more than 42 IU vitamin D per 100 g and that meets the requirements for foods named by use of a nutrient content claim and a standardized term in accordance with 21 CFR 130.10; breakfast cereals; grain-based bars; and yogurt and other cultured dairy products fermented with Lactobacillus delbrueckii, subspecies bulgaricus (L. delbrueckii, subsp. bulgaricus), and Streptococcus thermophilus (S. thermophilus). Vitamin D₂ bakers yeast is an approved food additive under § 172.381 for use as a source of vitamin D₂ and as a leavening agent in yeast-leavened baked goods and baking mixes and yeast-leavened baked snack foods. Vitamin D₂ mushroom powder is an approved food additive under § 172.382 for use as a source of vitamin D₂ in: (1) foods to which vitamin D₂, vitamin D₃, and vitamin D₂ bakers yeast are currently allowed to be added under §§ 184.1950, 172.379, 172.380, and 172.381, excluding cheese and cheese products, foods represented for use as a sole source of nutrition for enteral feeding, infant formula, milk and milk products, margarine, and grain-based bars; (2) fruit smoothies; (3) vegetable juices; (4) extruded vegetable snacks; (5) certain soups and soup mixes; and (6) plant protein products (see § 172.382(f)).

Vitamin D₂, also known as ergocalciferol, is the chemical 9,10-seco(5Z,7E,22E)-5,7,10(19),22-ergostatetraen-3-ol. The additive that is the subject of this petition is vitamin D₂ inactive bakers yeast that is produced by exposing bakers yeast to UV light, resulting in increased conversion of endogenous ergosterol to ergocalciferol. Under section 402(a)(7) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), sources of irradiation, such as UV light, must be used in accordance with a regulation or exemption in effect pursuant to section 409 of the FD&C Act.

To support their petition, Lallemand noted that the petitioned food uses and maximum use levels for vitamin D₂ inactive bakers yeast are the same, on a vitamin D₂ basis, as those for vitamin D₂ mushroom powder approved under § 172.382. Therefore, Lallemand concluded that the petitioned use of vitamin D₂ inactive bakers yeast would not increase the cumulative dietary exposure to vitamin D and referenced FDA's cumulative dietary exposure estimate for vitamin D in FAP 8A4821 (85 FR 41916, July 13, 2020). Lallemand compared the dietary exposure estimate to the Tolerable Upper Intake Level (UL) for vitamin D established by the Institute of Medicine (IOM) (now the National Academy of Medicine). Lallemand also submitted published scientific literature pertaining to clinical studies on vitamin D.

II. Evaluation of Safety

A. Vitamin D

To establish with reasonable certainty that a food additive is not harmful under its intended conditions of use, we consider the projected human dietary exposure to the additive, the additive's toxicological data, and other relevant information (such as published scientific literature) available to us. We compare the dietary exposure to the additive from all food sources to an acceptable intake level established by data. The dietary exposure is determined based on the amount of the ( printed page 60798) additive proposed for specific uses in foods and on data regarding the amount consumed from all food sources of the additive. We commonly use the 90th percentile dietary exposure for the consumer of a food additive as a measure of high chronic dietary exposure.

1. Acceptable Daily Intake for Vitamin D

In 2011, the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board at the IOM conducted an extensive review of relevant published scientific literature to update established dietary reference intakes (DRIs) for vitamin D; these DRIs are a family of nutrient reference values that includes ULs. Based on this information, the IOM revised the ULs for vitamin D and published a report on their findings (Ref. 3). In their 2011 assessment of vitamin D, the IOM established ULs for different age groups, including total consumption from food (including dietary supplements) and water:

The IOM considers the UL as the maximum daily intake level of a nutrient that is likely to pose no health hazard risk for almost all individuals in the general population when the nutrient is consumed over long periods of time. The UL is determined using a risk assessment approach developed specifically for nutrients. The dose-response assessment, which concludes with an estimate of the UL, is built upon three toxicological concepts commonly used in assessing the risk of exposures to chemical substances: no-observed-adverse-effect level (NOAEL), lowest-observed-effect level (LOEL), and application of an uncertainty factor. We considered the ULs established by the IOM relative to the cumulative dietary exposure estimates as the primary basis for assessing the safety of the petitioned uses of vitamin D₂. We also reviewed published scientific literature on the safety of vitamin D submitted in the petition, as well as other relevant published studies available to FDA (Ref. 4).

2. Dietary Exposure Estimate for Vitamin D

Lallemand stated that the petitioned food uses and maximum use levels for vitamin D₂ inactive bakers yeast are the same, on a vitamin D₂ basis, as those for vitamin D₂ mushroom powder authorized under § 172.382. Lallemand concluded that the petitioned uses of vitamin D₂ inactive bakers yeast would not increase the dietary exposure to vitamin D and therefore, it did not perform a new dietary exposure estimate for vitamin D from the petitioned uses. Because Lallemand considered the petitioned uses as substitutional for those in § 172.382, they referenced FDA's cumulative dietary exposure estimate for vitamin D in FAP 8A4821 (85 FR 41916), which resulted in the promulgation of § 172.382.

We note that the cumulative dietary exposure estimate referenced by Lallemand does not include the contribution to dietary exposure to vitamin D from FAP 9A4823 (88 FR 745, January 5, 2023) for the use of vitamin D₃ as a nutrient supplement in breakfast cereals at levels up to 560 IU/100 g and in grain-based bars at levels up to 400 IU/100 g. This estimate also does not include the contribution to the dietary exposure to vitamin D from the use of vitamin D₃ as a nutrient supplement in yogurt and other cultured dairy products fermented with L. delbrueckii, subsp. bulgaricus, and S. thermophilus at levels up to 178 IU/100 g from FAP 1A4827 (90 FR 42699, September 4, 2025). Furthermore, we note that the cumulative dietary exposure estimate referenced by Lallemand used food consumption data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES), and more recent NHANES food consumption data are available (Ref. 5).

The current cumulative eaters-only dietary exposure estimate to vitamin D ( i.e., cumulative dietary exposure to vitamin D for consumers of any or all foods petitioned for use) from all existing sources was discussed in FAP 1A4827 (90 FR 42699). Since the uses of vitamin D₂ inactive bakers yeast are substitutional for those in § 172.382, the cumulative eaters-only dietary exposure estimate would not change from that estimated in FAP 1A4827 (90 FR 42699).

For the overall U.S. population 1 year of age and older, the estimated cumulative dietary exposure at the 90th percentile from all food sources of vitamin D, including the proposed uses and background sources, is 3,170 IU/p/d. The estimated 90th percentile cumulative dietary exposure from all food sources of vitamin D is 944 IU/p/d for infants 0 to 6 months, 1230 IU/p/d for infants 6 to 12 months, 1720 IU/p/d for children 1 to 3 years, and 1910 IU/p/d for children 4 to 8 years. Estimated dietary exposures for adolescents, teenagers, and adults ranged from 1960 IU/p/d to 3930 IU/p/d. The estimated cumulative dietary exposure to vitamin D at the 90th percentile from the petitioned uses and background sources is below the IOM ULs for all population groups for which ULs were established (Ref. 5).

B. Safety of the Petitioned Uses of Vitamin D2 Inactive Bakers Yeast

FDA reviewed and evaluated the information submitted by Lallemand regarding the safety of UV light-treated inactive bakers yeast. FDA concludes that the use of UV light to produce vitamin D₂ inactive bakers yeast does not pose a safety concern, since the UV light treatment has been shown not to produce any new components of toxicological concern that could be introduced into the diet (Ref. 4).

In addition, we reviewed and evaluated the information submitted by Lallemand regarding the safety of the dietary exposure to vitamin D₂ from the proposed uses of vitamin D₂ inactive bakers yeast. Lallemand submitted reports of scientific studies published after the 2011 IOM report and issuance of the July 13, 2020, final order (85 FR 41916) for the uses of vitamin D₂ mushroom powder. Lallemand concluded that these publications support a conclusion that the proposed uses of vitamin D₂ are safe.

We reviewed the published reports of scientific studies on vitamin D submitted by Lallemand, as well as other relevant published studies available to us since our previous evaluations of food additive petitions for fortifying a variety of foods with vitamin D (90 FR 42699, September 4, 2025; 88 FR 745, January 5, 2023; 85 FR 41916, July 13, 2020; 81 FR 46578, July 18, 2016; 77 FR 52228, August 29, 2012; 74 FR 11019, March 16, 2009; 70 FR 69435, November 16, 2005; 70 FR 37255, June 29, 2005; 70 FR 36021, June 22, 2005; and 68 FR 9000, February 27, 2003). The studies did not raise any new safety concerns regarding the current or proposed uses of vitamin D. The most recent food additive petition concerning vitamin D resulted in our amendment of the food additive regulations in § 172.380 to authorize the use of vitamin D₃ as a nutrient supplement in yogurt and other cultured dairy products ( printed page 60799) fermented with L. delbrueckii, subsp. bulgaricus, and S. thermophilus at levels up to 178 IU vitamin D₃ per 100 g (90 FR 42699). The earlier food additive petitions also resulted in amendments of the food additive regulations to allow for the safe use of vitamin D as a nutrient supplement in certain foods.

We consider the ULs established by the IOM relative to the dietary exposure estimates as the primary basis for assessing the safety of the petitioned uses of vitamin D₂ . The estimated dietary exposure at the 90th percentile to vitamin D from all current and proposed food sources for each population group is less than the corresponding IOM UL for that population group. Considering that the petitioned uses of vitamin D₂ inactive bakers yeast are substitutional on a vitamin D₂ basis for the currently approved uses of vitamin D₂ mushroom powder, FDA concluded that the petitioned uses of vitamin D₂ inactive bakers yeast are not expected to increase the overall dietary exposure to vitamin D. Therefore, we conclude that the proposed uses of vitamin D₂ inactive bakers yeast are safe (Ref. 4).

III. Conclusion

Based on the relevant data available to FDA and information in the petition, we conclude that there is reasonable certainty that no harm will result from the uses of vitamin D₂ inactive bakers yeast, produced using UV light, as a source of vitamin D₂ within the limits proposed by Lallemand.

IV. Public Disclosure

In accordance with § 171.1(h) (21 CFR 171.1(h)), the petition and the documents that we considered and relied upon in reaching our decision to approve the petition will be made available for public disclosure (see FOR FURTHER INFORMATION CONTACT ). As provided in § 171.1(h), we will delete from the documents any materials that are not available for public disclosure.

V. Analysis of Environmental Impact

As stated in the December 29, 2021 (86 FR 74018) Federal Register notification of petition for FAP 1A4829, the petitioner claimed that this action is categorically excluded under 21 CFR 25.32(k) because it is to “approve a food additive petition for substances added directly to food that are intended to remain in food through ingestion by consumers and that are not intended to replace macronutrients in food.” We further stated that, if FDA determines the categorical exclusion applies, neither an environmental assessment nor an environmental impact statement is required. We did not receive any new information or comments regarding this claim of categorical exclusion. We considered the petitioner's claim of categorical exclusion and determined that this action is categorically excluded under 21 CFR 25.32(k). Therefore, neither an environmental assessment nor an environmental impact statement is required.

VI. Paperwork Reduction Act of 1995

This order contains no collection of information. Therefore, clearance by the Office of Management and Budget under the Paperwork Reduction Act of 1995 is not required.

VII. Objections

If you will be adversely affected by one or more provisions of this regulation, you may file with the Dockets Management Staff (see ADDRESSES) either electronic or written objections. You must separately number each objection, and within each numbered objection you must specify with particularity the provision(s) to which you object, and the grounds for your objection. Within each numbered objection, you must specifically state whether you are requesting a hearing on the particular provision that you specify in that numbered objection. If you do not request a hearing for any particular objection, you waive the right to a hearing on that objection. If you request a hearing, your objection must include a detailed description and analysis of the specific factual information you intend to present in support of the objection in the event that a hearing is held. If you do not include such a description and analysis for any particular objection, you waive the right to a hearing on the objection.

Any objections received in response to the regulation may be seen in the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at www.regulations.gov.

VIII. Section 301(ll) of the FD&C Act

Our review of this petition was limited to section 409 of the FD&C Act (21 U.S.C. 348). This order is not a statement regarding compliance with other sections of the FD&C Act. For example, section 301(ll) of the FD&C Act ( 21 U.S.C. 331 (ll)) prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act (21 U.S.C. 355), a biological product licensed under section 351 of the Public Health Service Act (42 U.S.C. 262), or a drug or biological product for which substantial clinical investigations have been instituted and their existence has been made public, unless one of the exemptions in section 301(ll)(1) through (4) of the FD&C Act applies. In our review of this petition, we did not consider whether section 301(ll) of the FD&C Act or any of its exemptions apply to food containing this additive. Accordingly, this order should not be construed to be a statement that a food containing this additive, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll) of the FD&C Act. Furthermore, this language is included in all food additive orders and therefore should not be construed to be a statement of the likelihood that section 301(ll) of the FD&C Act applies.

IX. References

The following references marked with an asterisk (*) are on display in the Dockets Management Staff (see ADDRESSES ) and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they are also available electronically at www.regulations.gov. References without asterisks are not on public display at www.regulations.gov because they have copyright restriction. Some may be available at the website address, if listed. References without asterisks are available for viewing only at the Dockets Management Staff. Although FDA has verified the website addresses in this document, please note that websites are subject to change over time.

* 1. Office of Dietary Supplements. “Vitamin D—Fact Sheet for Consumers.” U.S. Department of Health and Human Services, National Institutes of Health, Nov. 2022, ods.od.nih.gov/​factsheets/​Vitamind-Consumer/​.

* 2. Pilz, S., et al. “Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper.” Frontiers in Endocrinology, vol. 9, 2018, article 373, www.frontiersin.org/​articles/​10.3389/​fendo.2018.00373/​full.

* 3. IOM Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D, edited by A.C. Ross et al., National Academies Press, 2011, www.ncbi.nlm.nih.gov/​books/​NBK56070/​.

* 4. FDA Memorandum from A. Khan, Toxicology Review Branch, Division of Food Ingredients, to S. Fischer, Regulatory Management Branch, ( printed page 60800) Division of Food Ingredients, August 25, 2026.

* 5. FDA Memorandum from R. Shah, Chemistry Evaluation Branch, Division of Food Ingredients, to S. Fischer, Regulatory Management Branch, Division of Food Ingredients, August 25, 2026.

6. Parva, N.R., et al. “Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012).” Cureus, vol. 10, no. 6, 2018, article e2741, doi.org/​10.7759/​cureus.2741.

7. Corpas, E., et al. “Vitamin D and Calcium Deficiency in the Elderly.” Endocrinology of Aging: Clinical Aspects in Diagrams and Images, edited by E. Corpas et al., Academic Press, 2021, pp. 103-130, doi.org/​10.1016/​B978-0-12-819667-0.00004-4.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 172 is amended as follows:

91 FR 60796