Ketogenic diets are now being studied as therapeutic options for various conditions including diabetes, brain cancer, and neurological diseases. I first wrote about and published the notion that this dietary pattern may benefit many with ME/CFS given its therapeutics effects in other conditions. While it’s true that the diet has exploded into a modern day diet fad, there are still many, many reasons to raise a curious eyebrow to the research surrounding it. Let’s take a look at the latest research that continues to make this diet a viable option for those with ME/CFS, and clinical trials of ketogenic diets in other chronic conditions.

What Does a Keto Diet Look Like?

After a couple of days of drastic reduction of dietary carbohydrates, or <20 grams of carb per day or 5% of total daily calorie intake, the body is forced to break down fats to free fatty acids which serve as a primary fuel source. The brain cannot use free fatty acids as fuel, however, because they do not cross the blood-brain barrier. These fats are then converted to ketones by the liver. The liver produces 3 primary ketones: β-hydroxybutyrate (BHB), acetate, and acetoacetate (AcAc). Most important and best-studied of these is BHB, which has potent effects on the expression of certain genes and can communicate with various aspects of cell signaling.

How Does Keto Help Symptoms?

The verdict is still out as to the precise reasons ketogenic diets have beneficial effects in certain conditions. For example, in diabetes it could be the weight loss that improves the condition, not the specific diet itself. Clearer however are the neurological properties, including the anti-seizure effects, that it purports. The neuroprotective effect of a ketogenic diet is believed to be due to influences on inflammatory cytokines and an oxidative stress reduction.

On the flip side, the benefits seen in the diet may also be due to changes in brain metabolism. The major ketone body, BHB, provides more energy for the brain per unit of oxygen than glucose. In this way, a ketogenic diet enhances production of cellular energy; ATP. In so doing, there is the added benefit of reduced free radical production at the mitochondria and preservation of the delicate mitochondrial membrane.

Studies in mice have revealed the intrinsic antioxidant effect of the diet. Specifically in the region of the hippocampus, an area crucial for memory formation and spatial cognition, the ketogenic diet enhances antioxidant defenses by boosting glutathione production. These same mechanisms are believed to at least partly explain the dramatic benefits those with Parkinson’s and Alzheimer’s have with this diet.

So What About Keto for ME/CFS?

The above general effects of ketogenic diets may play a substantial role in reducing symptoms in those with ME/CFS. Reducing oxidative stress, improving mitochondrial function, and boosting glutathione production—especially in the central nervous system— target some central aspects of the condition. Here are a few other possible mechanisms, learned from other conditions, that may benefit those with ME/CFS.

• In the gut, the ketone body BHB reduces lactate and increases serotonin release from the intestinal cells. Increased lactate and low serotonin levels have been found in some studies of ME/CFS.

• In the brain, ketone bodies like BHB shift the balance of GABA/glutamine, making neurons less excitable. It also improves cerebral blood flow as seen in patients with traumatic brain injury. Low cerebral blood flow has long been associated with ME/CFS.

• Ketogenic diets improve blood-brain barrier integrity reducing “leaky brain,” a potential finding in recent ME/CFS neuroimaging.

• The low blood glucose levels associated with ketogenic diets stimulate the release of growth hormone, a hormone found reduced in some studies of ME/CFS and several studies of fibromyalgia.

• Ketogenic diets reduce circulating levels of insulin and insulin-like growth factors (IGF-1). Chronic oxidative stress seen in ME/CFS, reduces insulin sensitivity making cells poorer at taking up glucose to make ATP.

Clinical Trials

A 2018, randomized controlled trial for 6 months recruited MS patients to participate in a ketogenic diet, caloric-restricted diet, or control diet. Those on the ketogenic diets and restricted diet showed a reduction in the expression of enzymes involved in the biosynthesis of pro-inflammatory molecules. These findings also corresponded with self-reported improvements in quality of life.

One of the most impressive ketogenic clinical trials to date comes from a 1 year, controlled trial of 349 individuals with type II diabetes. At the end of the trial, there were significant reductions in medication usage, weight loss, and improved blood biomarkers of blood sugar regulation. While this is specific to type II diabetes, it should still allay some fears of a ketogenic diet for any that want to try. This study is an excellent example of the safety and efficacy of nutritional ketosis when long-term and well-designed.

A 2018 study of the ketogenic diet in Parkinson’s disease compared to a low-fat diet showed improvement in motor symptoms in both groups after 8 weeks of the diet trial. However, the ketogenic diet group also experienced improvement in non-motor symptoms of Parkinson’s disease including fatigue, pain, and cognitive impairment.  

An 2004, clinical trial of 20 subjects with Alzheimers disease or mild cognitive impairment were given a drink either containing medium chain triglycerides (MCTs) or a placebo. The group that received MCTs showed significant increases in levels of β-hydroxybutyrate 90 minutes after ingestion. Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to the placebo across all subjects. This is only a single example of many clinical trials along these lines. Ongoing trials of ketogenic diets with or without ketone supplementation are taking place at Johns Hopkins, Wake Forest, University of British Columbia, and Universite de Sherbrooke. More on supplemental ketones in the next post…

Has a ketogenic diet benefited your ME/CFS or Fibromyalgia symptoms?

References

Boison D. (2017) New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol. 30(2):187-192.

Bock, M. et al (2018) Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis. EBioMedicine, Volume 36, 293 – 303.

Shen Y. et al. (2017) Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP. Nature Communications: 8:624.

Paoli, A. et al. (2019) Ketogenic Diet and Microbiota: Friends or Enemies? Genes. 10(7), 534.

Hallberg SJ et al. (2018) Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Ther. 9(2):583-612.