Washington, DC—The Council for Responsible Nutrition (CRN) announced the publication of new and updated chapters in its Vitamin & Mineral Safety, Fourth Edition (VMS4) series. The content expands this comprehensive, science-based resource on nutrient safety. The latest updates include:

A new safety evaluation for choline and citicoline.

These are essential nutrients for brain and liver health. Based on data from more than 20 human clinical trials, and consistent with prior evaluations by the Institute of Medicine (IOM), CRN reaffirmed IOM’s UL of 3,500 mg per day for choline and derived a new supplemental UL of 2,000 mg per day for citicoline. This new content also reviews recent observational studies exploring possible links between choline intake and cardiovascular disease (CVD) outcomes; CRN determined that a clear relationship between dietary choline intake and CVD outcomes cannot be established from the current body of evidence. “This new chapter closes a long-standing gap in nutrient safety guidance,” said Andrea Wong, Ph.D., Senior Vice President, Scientific & Regulatory Affairs, CRN. “Choline and citicoline play vital roles in cognition, liver health, and metabolism—and the evidence confirms their safety when consumed at reasonable supplemental levels.”

A new chapter on lutein, zeaxanthin, and meso-zeaxanthin.

These carotenoids are associated with vision and eye health. Building upon CRN’s earlier risk assessment for lutein (Shao and Hathcock, 2006), the updated review draws from approximately 75 human clinical trials and global evaluations by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA). CRN reported that no serious adverse effects were identified across studies, even at doses far exceeding typical dietary intakes. Based on the available data, CRN maintained the Highest Observed Intake (HOI) of 22 mg per day for lutein previously established in 2006, and established an HOI of 26 mg per day for zeaxanthin and 17 mg per day for meso-zeaxanthin. “This chapter offers the most updated picture of the clinical safety of lutein, zeaxanthin, and meso-zeaxanthin,” said Dr. Wong. “It affirms these bioactives’ strong safety record and their important contribution to visual health.”

An updated folate chapter.

This new content reaffirms the existing UL of 1 mg per day for folic acid. This chapter also includes a new section on methylfolate (5-MTHF)—the active form increasingly featured in supplements and fortified foods.The updated review synthesizes the latest findings on the safety, metabolism, and bioavailability of methylfolate, establishing a UL of 1.5 mg per day. “Our updated folate chapter provides clarity for today’s market,” said Dr. Wong. “By distinguishing folic acid and methylfolate, CRN is helping ensure safety standards keep pace with innovation.”

An updated Vitamin K2 (menaquinone-7, MK-7) chapter.

The evaluation established a supplemental HOI level of 375 µg/day for adults. Previous editions of CRN’s Vitamin & Mineral Safety derived a single UL value for vitamin K, encompassing vitamin K1 and vitamin K2. Given the growing consumer interest and use of vitamin K2 supplements worldwide, a separate assessment was conducted for vitamin K2, specifically MK-7. CRN noted that this offers essential new guidance for manufacturers, regulators, and health practitioners seeking evidence-based recommendations for this nutrient, which is widely recognized for its role in supporting bone and cardiovascular health. “CRN’s updated MK-7 chapter reflects our commitment to providing rigorous, transparent safety evaluations grounded in the totality of evidence,” said Dr. Wong. “Establishing a HOI for Vitamin K2 (MK-7) represents a major step forward for scientific understanding and responsible product development across the dietary supplement category.”

The new content is accessible at www.crnusa.org/resources/vitamin-mineral-safety. Additional nutrient reviews are scheduled for release throughout 2026.

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