Exogenous Ketones for ME/CFS, Fibro & Long COVID: Benefits

(updated June 2025)

What Are Exogenous Ketones and How Do They Work?

Exogenous ketones are supplements that raise blood levels of beta-hydroxybutyrate (BHB)—a ketone body that supports mitochondrial function, reduces oxidative stress, and modulates inflammation. For individuals with chronic fatigue syndrome (ME/CFS), fibromyalgia, or long COVID, this offers a potential energy source that bypasses dysfunctional glucose metabolism.

Unlike endogenous ketones, which are produced by the liver during fasting or a ketogenic diet, exogenous ketones deliver BHB directly through supplementation. This can result in rapid cognitive and energy benefits—without the dietary rigidity of ketosis.

Best Ketone Supplements for ME/CFS and Chronic Illness

There are three main forms of exogenous ketones, each with unique pros and cons for sensitive patients:

BHB Salts vs Esters vs Butanediol

• BHB Salts: Combine BHB with minerals like sodium, potassium, or magnesium. These are common and inexpensive but can cause GI distress and electrolyte overload at high doses. Many contain racemic (D+L) BHB, though only D-BHB is biologically active.

• Ketone Esters: The most effective option. Pure D-BHB esters rapidly raise blood ketones to 2–3+ mmol/L, supporting brain energy and mitochondrial output. However, they can cause nausea if taken too quickly or on an empty stomach.

• R-1,3-Butanediol: A precursor converted to D-BHB in the liver. Gentler on the gut, slower to raise BHB, and well-tolerated in sensitive individuals. A good option for daily use or those with gastrointestinal sensitivity.

Which Ketone Supplements Are Easiest on the Stomach?

For those with postviral GI issues or autonomic dysfunction, tolerability matters just as much as potency.

• Best for Sensitive Stomachs:
  HVMN Ketone-IQ (R-1,3-butanediol) — slow, steady, and very low GI side effects.

• Most Clinically Researched:
  ΔG Ketone Ester or KE4 Pro — used in Alzheimer’s and performance studies, but best diluted and taken with food.

• Balanced Blend:
  Juvenescence Metabolic Switch — D-BHB combined with MCT oil for a milder yet effective formula.

Avoid generic BHB powders with unclear D/L ratios, as the L-isomer is not metabolized and may lead to side effects without therapeutic benefit.

Do Exogenous Ketones Work Without a Ketogenic Diet?

Yes. While ketone supplements work best with reduced carbohydrate intake, they can still be effective even if you're not strictly keto. For postviral patients, a moderate-carb, low-sugar diet (20–30% carbs) can be a good match.

Many people with ME/CFS or long COVID already eat lower carb for gut or blood sugar reasons, making BHB supplementation a logical add-on—without further dietary restriction.

Research-Backed Benefits of Exogenous Ketones

Growing research supports BHB as a neuroprotective and mitochondrial-enhancing molecule.

Brain Fog, Fatigue, and Mitochondrial Support

• A randomized controlled trial found that raising BHB levels via a ketogenic drink improved memory recall in patients with mild cognitive impairment (Fortier et al., 2019).

• BHB reduces oxidative stress, upregulates mitochondrial biogenesis, and acts as a histone deacetylase (HDAC) inhibitor, all of which support brain and muscle energy metabolism (Achanta & Rae, 2016; Kovács et al., 2019).

• In ME/CFS and long COVID, where glucose metabolism is impaired, ketones may serve as a preferred alternate fuel source.

How to Use Exogenous Ketones Safely

• Start low: Especially with esters or salts. Begin with ¼ to ½ dose to test tolerance.

• Take with food or fluids: Esters can cause nausea if taken undiluted or on an empty stomach.

• Avoid stacking salts and MCT oil: This can overwhelm the gut in sensitive users.

• Stay hydrated: Especially if using salts, which deliver a significant electrolyte load.

Why Consider Exogenous Ketones in Chronic Illness?

For those living with postviral fatigue, cognitive dysfunction, or mitochondrial insufficiency, exogenous ketones offer:

• A rapid, clean energy source for the brain and muscles

• Reduced inflammation and oxidative stress

• Flexible use—no need for full dietary ketosis

• A tool to improve mental clarity and potentially exercise recovery

They’re not a cure—but they are a powerful adjunct for those managing complex chronic illness.

References

Achanta, L. B., & Rae, C. D. (2016). β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms. Neurochemical Research, 42(1), 35–49.

Fortier, M., et al. (2019). A ketogenic drink improves cognition in mild cognitive impairment: results of a 6-month RCT. Alzheimer’s & Dementia, 15(5), 625–634.

Hashim, S. A., & VanItallie, T. B. (2014). Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. Journal of Lipid Research, 55(9), 1818–1826.

Kovács, Z., et al. (2019). Therapeutic potential of exogenous ketone supplement-induced ketosis in the treatment of psychiatric disorders: review of current literature. Frontiers in Psychiatry, 10, 363.

Stubbs, B. J., et al. (2017). On the metabolism of exogenous ketones in humans. Frontiers in Physiology, 8, 848.

Stubbs, B. J., et al. (2017). Exogenous ketone supplements reduce appetite and lower blood glucose in overweight individuals. Metabolism, 66, 11–17.