Valproic Acid and Liver Health: Exploring the Protective Potential of Vitamin U.

Vitamin U-rich cruciferous vegetables, such as cabbage and broccoli, may help protect liver function from valproic acid-related toxicity. A Melbourne dietitian can provide personalised nutrition advice to support liver health and medication tolerance.

Valproic acid (VPA) is a widely prescribed medication for neurological and psychiatric disorders such as epilepsy, bipolar disorder, and migraine prevention. Despite its effectiveness, VPA’s use has been linked to hepatotoxicity, ranging from mild increases in liver enzymes to rare but severe liver failure. Kadam et al. (2025) provide a detailed review of the mechanisms behind VPA-induced liver injury, emphasizing oxidative stress, mitochondrial dysfunction, and carnitine depletion as key contributors to its hepatotoxic effects [1].

Given the potential risks of VPA therapy, there is increasing interest in natural compounds with hepatoprotective properties. One promising candidate is S-methylmethionine (SMM), commonly known as vitamin U. Although not a true vitamin, vitamin U has been investigated for its beneficial effects on gastrointestinal health and liver protection [2].

Understanding Vitamin U and Its Biological Role

Vitamin U is a derivative of the essential amino acid methionine, predominantly found in cruciferous vegetables like cabbage, broccoli, Brussels sprouts, kale, and spinach. Historically, vitamin U gained attention in the 1950s when raw cabbage juice was observed to promote healing in patients with peptic ulcers. More recently, its antioxidant, anti-inflammatory, and cytoprotective properties have been explored, particularly regarding liver and gut health [2].

A notable study on broiler chickens demonstrated that vitamin U supplementation improved liver performance and enhanced intestinal tract integrity, indicating a systemic benefit to both hepatic function and digestive health [4]. These findings suggest that vitamin U may support cellular repair and maintain organ health under stress conditions.

Vitamin U’s Hepatoprotective Effects in VPA-Induced Liver Injury

Research using animal models provides compelling evidence for vitamin U’s liver-protective potential. For example, Sokmen et al. (2012) showed that vitamin U administration significantly reduced liver damage caused by VPA in rats. This protection was attributed to vitamin U’s ability to diminish oxidative stress markers and preserve the structural and functional integrity of liver tissue [3].

The mechanism likely involves vitamin U’s antioxidant action, which helps neutralize reactive oxygen species generated during VPA metabolism. Additionally, vitamin U may support mitochondrial function and promote detoxification pathways, thereby reducing hepatocyte injury [1,3].

Dietary Sources and Practical Recommendations

Vitamin U is naturally abundant in many everyday vegetables, making dietary inclusion a safe and accessible way to potentially support liver health. Key sources include:

• Cabbage

• Broccoli

• Brussels sprouts

• Kale

• Spinach

While vitamin U supplements exist, getting this compound through diet remains the most recommended and safest approach, especially for those taking VPA or other hepatotoxic drugs. However, it is crucial for patients to consult their healthcare providers before making significant dietary changes or beginning supplements, to ensure compatibility with their treatment plans.

Conclusion

Valproic acid remains a vital medication in managing epilepsy, bipolar disorder, and migraines, but its risk of liver toxicity demands attention to liver health. Vitamin U, found abundantly in cruciferous vegetables, offers promising hepatoprotective effects through antioxidant and cytoprotective mechanisms. Animal studies show that vitamin U can mitigate VPA-induced liver damage and improve intestinal health, suggesting a multifaceted role in supporting organ function [1,3,4].

Although more robust clinical trials in humans are needed to fully validate these benefits, incorporating vitamin U-rich foods into the diet may serve as a complementary strategy to help safeguard liver function during VPA therapy.

References

1. Kadam R, Palkar M, Pingili RB. Mechanisms involved in the valproic acid-induced hepatotoxicity: a comprehensive review. Toxicol Mech Methods. 2025 Feb 6:1-16. doi: 10.1080/15376516.2025.2459176. Epub ahead of print. PMID: 39871487.

2. Clinical Education. The Use Of Vitamin U For Gastric Ulcer Recovery. https://www.clinicaleducation.org/resources/reviews/the-use-of-vitamin-u-for-gastric-ulcer-recovery/

3. Sokmen B, Tunali S, Yanardag R. Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats. Food Chem Toxicol. 2012;50(10):3562–6. doi:10.1016/j.fct.2012.07.056

4. Al-Kassie GAM, Roshdy NM, El-Kholy MMS. Effects of Vitamin U on Live Performance and Intestinal Tract Integrity in Broilers. Int J Poult Sci. 2013;12(1):30–35. Available from: https://www.researchgate.net/publication/233172325_Effects_of_Vitamin_U_on_Live_Performance_and_Intestinal_Tract_Integrity_in_Broilers