This Ancient Chinese Herb Mimics the Ketogenic Diet to Fight Colitis, Without the Side Effects

If you have ulcerative colitis (UC), the chronic inflammatory bowel disease that causes painful flares, bloody stools, and relentless gut damage, you have probably heard that diet matters. Some researchers have been investigating the ketogenic diet (KD), an extreme low-carbohydrate, high-fat eating pattern that forces the liver to produce molecules called ketone bodies, as a way to dial down intestinal inflammation. The problem is that the KD is hard to sustain, and it carries real risks including fatigue, diarrhea, elevated uric acid, and, in severe cases, ketoacidosis. A new study published in Food Science and Nutrition asks whether a traditional Chinese herb called Rehmannia glutinosa could raise ketone body levels and ease UC in mice without forcing any of those dietary changes. The results are preliminary, but they are thought-provoking.

Key takeaways:

• Rehmannia glutinosa extract (1.5 g/kg/day) significantly raised ketone body levels in UC mice and reduced intestinal inflammation comparably to a ketogenic diet.
• The likely mechanism involves suppression of the STAT3 signaling pathway, which drives inflammatory cascades in the gut lining.
• Unlike the ketogenic diet, the herb extract did not raise uric acid or disturb blood glucose or insulin, suggesting a cleaner metabolic profile in this mouse model.
• This is early-stage animal research; no human trials exist, and the active compounds driving the ketogenic effect have not been confirmed.

Rehmannia glutinosa extract raised ketone bodies and eased ulcerative colitis in mice

The core finding is straightforward: daily oral doses of Rehmannia glutinosa extract (abbreviated DH in the study, from the Chinese name Dihuang) significantly elevated both blood and colon ketone body levels in mice with DSS-induced UC (a standard laboratory model of the disease). Ketone bodies, chiefly beta-hydroxybutyrate (βOHB), acetoacetate, and acetone, are not just fuel molecules; they function as anti-inflammatory signaling agents that can limit the runaway immune activation underlying conditions like UC. Research has documented how ketone bodies modulate inflammation and oxidative stress through multiple pathways, including inhibiting the inflammasome complex that amplifies immune flares. What is novel here is that DH appeared to boost ketone production without requiring any shift away from a normal diet.

On the disease outcome measures that matter most for UC, DH performed comparably to both a ketogenic diet and mesalazine (5-ASA), a standard first-line UC medication. Treated mice lost less body weight, had lower disease activity index scores (a combined measure of stool consistency, blood, and weight loss), and showed less colon shortening and mucosal damage than untreated UC controls.

How Rehmannia glutinosa outperformed the ketogenic diet on safety markers

The metabolic side-effect profile is where DH separated itself from the KD most clearly. The ketogenic diet, as expected, significantly lowered plasma glucose, triglycerides, and insulin, but it also raised uric acid, a marker associated with gout and kidney stress. DH intervention only reduced triglyceride levels, with no significant impact on blood glucose, insulin, or uric acid. Hepatic (liver) and renal (kidney) function indicators also remained stable in the DH group. For someone managing a chronic condition like UC who cannot afford additional metabolic complications, that distinction matters.

DH also showed superior antioxidant effects compared to the KD on markers like superoxide dismutase (SOD), an enzyme the body uses to neutralize harmful free radicals. On inflammatory markers including TNF-alpha and IL-6, two cytokines (cell-signaling proteins) central to the gut inflammation in UC, DH performed at least as well as the KD. This suggests that some of DH's benefits may come from bioactive compounds in the herb itself, such as polysaccharides, catalpol, and ajugol, rather than solely from ketone body production. Catalpol, one of Rehmannia's active ingredients, has separately shown metabolic benefits in other inflammatory contexts, and broader network pharmacology analyses have mapped Rehmannia glutinosa's wide anti-inflammatory and immune-modulating potential across multiple diseases.

How the study was designed and what it measured

Researchers used C57BL/6J mice with UC induced by dextran sulfate sodium (DSS), a well-established laboratory method that damages the colon lining in a way that resembles human UC. Animals were divided into groups receiving normal diet, ketogenic diet, the UC drug mesalazine, or DH extract at 1.5 g/kg per day. The team used molecular docking (computational modeling of how molecules bind to proteins) to identify which DH components might interact with two key ketogenesis enzymes: BDH1 (beta-hydroxybutyrate dehydrogenase 1) and HMGCS2 (HMG-CoA synthase 2), both of which are critical for ketone body production in the liver. Rehmannioside D, one of the herb's active components, showed strong predicted binding to both proteins. Enzyme activity assays then confirmed that DH increased the functional activity of BDH1 and HMGCS2 in mouse livers, though it did not change how much of these enzymes the liver produced, suggesting it activates existing enzyme rather than upregulating gene expression.

Statistical analysis used one-way ANOVA and Spearman's correlation, which confirmed that βOHB levels significantly correlated with suppression of p-STAT3 (phosphorylated STAT3) and caspase-1, both key drivers of the inflammatory cascade in UC.

What this means if you have ulcerative colitis

The STAT3 pathway connection is worth understanding if you follow UC research. STAT3 is a transcription factor, essentially a molecular switch, that regulates immune responses. When it is overactivated, it promotes caspase-1 activity, which in turn drives rapid production of inflammatory molecules like IL-1beta and IL-18. Both DH and the KD suppressed p-STAT3 and caspase-1 in this study, and the strength of that suppression correlated directly with ketone body levels. The researchers interpret this to mean that boosting ketone bodies, whether through diet or through a plant extract, may be a viable strategy for quieting this particular inflammatory circuit in UC. Ketone bodies as signaling molecules have attracted growing interest precisely because they appear to influence autoimmune and inflammatory diseases beyond their classic role as fuel.

For someone managing UC, this is interesting but not yet actionable. There are no human trials. The dose used in mice does not translate directly to a human dose, and Rehmannia products sold as supplements vary enormously in composition and standardization. A Korean literature review on Rehmanniae Radix found broadly favorable safety signals for inflammatory and metabolic conditions, but that is not the same as evidence for UC specifically. Do not interpret this study as a reason to self-supplement; bring it to a gastroenterologist or integrative medicine physician who can evaluate it in the context of your treatment plan.

Key limitations and what researchers still need to confirm

The authors are candid about what this study cannot yet establish. The mouse model used DSS-induced UC, which captures some but not all aspects of the human disease. The study did not include microbiome analysis, so whether DH alters gut bacteria in ways that contribute to its effects remains unknown. The specific active compounds responsible for the ketogenic effect have not been confirmed beyond molecular docking predictions. It is also unclear whether DH influences other ketogenesis enzymes beyond BDH1 and HMGCS2, or whether it suppresses STAT3 through upstream regulators like JAK2. No pharmacokinetic data, no tissue distribution analysis, and no long-term safety data in healthy animals exist yet.

What comes next in Rehmannia glutinosa research

The researchers call for follow-up studies that include intermediate ketone level monitoring, NLRP3 inflammasome analysis, and inhibitor experiments to confirm the proposed mechanism chain from ketone body elevation to STAT3 suppression to reduced colitis damage. Human pharmacokinetic studies would need to follow before any clinical application could be considered.

Common questions

Can I take Rehmannia glutinosa supplements for my UC now? Not based on this study. The evidence comes entirely from a mouse model, and no human trials have tested DH for UC. Standard UC treatments have decades of safety and efficacy data behind them; do not replace or reduce them without medical guidance.

Does a ketogenic diet actually help ulcerative colitis? Animal studies and some small human reports suggest a ketogenic diet can reduce gut inflammation, but rigorous human clinical trials in UC are limited. The diet is also difficult to sustain and carries metabolic risks for some people, particularly those with kidney issues.

What is beta-hydroxybutyrate and why does it matter for gut inflammation? Beta-hydroxybutyrate (βOHB) is the main ketone body produced during fat metabolism or fasting. Beyond serving as fuel, it acts as a signaling molecule that can inhibit inflammatory pathways, including the NLRP3 inflammasome and STAT3 activation, both of which are implicated in UC flares.

How is Rehmannia glutinosa normally used? In traditional Chinese medicine, Rehmannia glutinosa root is used for a broad range of conditions. Modern research has begun identifying active compounds like catalpol, rehmannioside D, and various polysaccharides with anti-inflammatory and metabolic properties, though most studies remain at the cell or animal level.

References

1. Yiqiao Gao, Simiao Wang, Yuye Yang, Wei Tang, Jianhan Zhen, Xiangshi Song (2026). Rehmannia glutinosa Extracts Enhances Ketone Bodies Expression and Alleviates Ulcerative Colitis as A Novel Ketogenic Functional Food. Food Science & Nutrition. https://doi.org/10.1002/fsn3.72263
2. Patrycja Puchalska, Peter A. Crawford (2021). Metabolic and Signaling Roles of Ketone Bodies in Health and Disease. Annual Review of Nutrition. https://doi.org/10.1146/annurev-nutr-111120-111518
3. Jinyoung Park, Muhammad Yasir, Eun-Taek Han, et al. (2025). Exploring the Therapeutic Potential of Rehmannia glutinosa: A Network Pharmacology and Molecular Docking Analysis Across Multiple Diseases. Current Issues in Molecular Biology. https://doi.org/10.3390/cimb47050329
4. Yanmei Gong, Yifan Wei, Ying Liu, Tong Du (2026). The value of targeting ketone body metabolism in inflammatory and autoimmune diseases. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-07884-x
5. Rehmanniae Radix, an Effective Treatment for Patients with Various Inflammatory and Metabolic Diseases: Results from a Review of Korean Publications – PMC. NIH. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446419/