When people have severe infections (sepsis), their muscles become dangerously weak. Scientists wondered if giving patients special high-fat nutrition through IV tubes might help by triggering their body to make ketones—a type of fuel that previous studies showed could protect muscles. Researchers tested this idea in mice with sepsis, trying different combinations of fats and sugar. They found that pure fat did create ketones, but it actually made muscle weakness worse. Adding sugar helped the muscles but stopped the body from making ketones. The results suggest that simply giving more fat isn’t the answer—the balance between fat and sugar matters a lot.

The Quick Take

  • What they studied: Whether special high-fat nutrition given through IV tubes could help sepsis patients maintain muscle strength by triggering their body to produce ketones (an alternative fuel source)
  • Who participated: Laboratory mice with sepsis (severe infection), divided into different groups receiving different types of fat and sugar combinations, compared to healthy control mice
  • Key finding: Pure fat created ketones in the body but worsened muscle weakness, while adding sugar protected muscles but prevented ketone production—neither approach alone solved the problem
  • What it means for you: This research suggests that for sepsis patients, simply increasing fat intake through IV nutrition may not be the solution. The balance between fats and carbohydrates appears critical, and more research is needed before changing how doctors feed critically ill patients

The Research Details

Scientists used mice with sepsis (a life-threatening infection) that were fed entirely through IV tubes, similar to how critically ill humans are sometimes fed. They conducted two separate experiments. In the first experiment, some mice received standard IV nutrition, while others received pure fat (long-chain triglycerides) or fat mixed with glucose (sugar). In the second experiment, they compared fat mixed with sugar to a different type of fat mixture also combined with sugar. After 5 days, researchers measured ketone levels in the blood, tested muscle strength, and examined how the muscles and liver were functioning at a cellular level.

This approach allowed scientists to test specific combinations in a controlled way before considering human trials. By using mice with sepsis, they could study the exact problem they wanted to solve—muscle weakness during severe infection—while controlling all the variables that might affect the results.

The study design was important because it allowed researchers to isolate which components (fat type, fat amount, sugar content) actually affected ketone production and muscle strength, rather than guessing based on theory alone.

Understanding how to feed sepsis patients is critically important because severe infections cause rapid muscle loss that can take months to recover from, even if the infection is treated. If doctors could prevent this muscle weakness through better nutrition, patients would recover faster and have fewer complications. This research matters because it tests whether a specific mechanism—ketone production—could be the key to protecting muscles during sepsis.

This study was conducted in a controlled laboratory setting with mice, which allows for precise measurement of biological markers but may not perfectly reflect what happens in human bodies. The researchers measured multiple markers (ketone levels, muscle function, cellular changes) rather than relying on a single measurement, which strengthens confidence in the findings. However, because this is animal research, results need confirmation in human studies before changing medical practice. The study was published in a peer-reviewed journal focused on intensive care research, suggesting it met scientific standards for publication.

What the Results Show

When septic mice received pure fat without sugar, their bodies produced significant amounts of ketones (1.39 mmol/L), which was much higher than the standard IV nutrition group. However, these mice with high ketone levels actually had worse muscle weakness than the control group—the opposite of what researchers hoped.

When glucose (sugar) was added to the fat, muscle weakness improved compared to pure fat alone. But this improvement came at a cost: adding sugar almost completely stopped the body from producing ketones. The mice receiving fat plus sugar had ketone levels similar to the standard nutrition group, meaning the ketone-producing benefit was lost.

In the second experiment comparing different types of fat mixtures, both with added sugar, neither combination produced adequate ketones or prevented muscle weakness. Additionally, the researchers found that a key enzyme needed to make ketones (called Hmgcs2) was suppressed when sugar was added to the fat mixture.

The research revealed that the relationship between ketone production and muscle protection is more complex than previously thought. Simply triggering ketone production wasn’t enough—in fact, high ketones without sugar actually worsened the problem. This suggests that the body needs both ketones and glucose working together, or that the process of making ketones without adequate glucose may create other problems that harm muscles. The cellular analysis showed differences in how muscles and liver processed nutrients depending on the fat and sugar combinations, indicating that these nutrients affect multiple body systems simultaneously.

Earlier studies had shown that giving ketone bodies directly to sepsis patients appeared to help protect muscles. This new research suggests that simply stimulating the body to make its own ketones through high-fat nutrition may not work the same way. The difference might be that directly providing ketones is different from forcing the body to produce them, or that the balance of nutrients matters more than any single component. This finding contradicts the simple assumption that ‘if ketones help, then making more ketones should help more.’

This study was conducted in mice, not humans, so results may not directly apply to sepsis patients. The researchers didn’t specify exactly how many mice were used in each group, making it harder to assess the strength of the findings. The study only lasted 5 days, while human sepsis recovery takes much longer. The mice were fed entirely through IV tubes, which is similar to some human patients but not all. Additionally, the study measured biological markers (like ketone levels) but didn’t follow long-term outcomes like survival or full recovery. The research doesn’t explain why pure fat worsened muscle weakness, leaving important questions unanswered.

The Bottom Line

Based on this research, doctors should NOT simply switch sepsis patients to high-fat, low-carbohydrate IV nutrition in hopes of triggering ketone production. The evidence suggests this approach could actually worsen muscle weakness. Current standard IV nutrition appears safer until more research clarifies the best balance of fats and carbohydrates. If ketone-based therapy is considered, providing ketones directly (rather than trying to stimulate the body to make them) may be more effective, but this needs further study. Confidence level: Moderate—this is animal research that needs human confirmation.

This research is most relevant to doctors and nutritionists who care for critically ill sepsis patients in intensive care units. It’s also important for researchers developing new nutrition strategies for severe infections. Family members of sepsis patients should know that while nutrition is important during recovery, the specific approach tested here (high-fat, low-carb IV feeding) doesn’t appear to be the answer based on current evidence. People without sepsis don’t need to change their diet based on this research.

In the mice studied, changes in muscle weakness and ketone levels appeared within 5 days. If similar approaches were tested in humans, it would likely take weeks to months to see meaningful changes in muscle strength and recovery. However, this research doesn’t yet support trying this approach in humans, so realistic timelines for human application cannot be determined.

Want to Apply This Research?

  • For users recovering from sepsis or severe illness: Track daily muscle strength using simple tests (time to walk 10 steps, ability to climb stairs, grip strength with a hand dynamometer) and record weekly. This provides objective data on recovery progress independent of how you’re being fed.
  • If you’re recovering from sepsis and receiving IV nutrition, work with your medical team to ensure your nutrition includes both adequate fat and carbohydrates rather than emphasizing one over the other. Don’t request high-fat, low-carb IV nutrition based on this research—instead, ask your doctor about balanced nutrition approaches supported by current evidence.
  • Track muscle function recovery over weeks and months using consistent, measurable activities (walking distance, stair climbing, grip strength). Record any changes in fatigue levels and ability to perform daily activities. Share this information with your healthcare team to help guide nutrition decisions and overall recovery planning.

This research was conducted in mice and has not been tested in humans. It should not be used to guide personal medical decisions about nutrition during sepsis or critical illness. If you or a loved one has sepsis or is receiving IV nutrition in a hospital, all nutrition decisions must be made with your medical team based on your individual condition. Do not request changes to IV nutrition based on this research without consulting your doctor. This summary is for educational purposes only and does not replace professional medical advice.