There are several variations of the ketogenic (aka keto) diet, but it primarily includes high levels of fat, moderate to high levels of protein, and low levels of carbohydrates. Ketogenic diets are known to be helpful in weight loss and obesity, and this success is encouraging researchers to look into additional clinical applications. 

 

Alcohol use disorder

 

In a US-based study published in the journal Science Advances, researchers evaluated if metabolic ketosis from a ketogenic diet had a therapeutic benefit in managing cravings and withdrawal symptoms for inpatients with alcohol use disorder undergoing detoxification.

Wiers CE, Vendruscolo LF, van der Veen JW, et al. Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. Sci Adv. 2021;7(15):eabf6780.

The researchers also studied if a ketogenic diet would reduce alcohol drinking during acute withdrawal in a rat model of alcohol dependence.

 

They therefore surmised that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in alcohol use disorder, and that a ketogenic diet may mitigate these effects. Using the rat study as a preclinical surrogate for the effects of a ketogenic diet on alcohol cravings, the investigators applied the learnings to the human trial. 

The results of the human study showed that patients with alcohol use disorder who were randomized to receive a ketogenic diet required less benzodiazepine medication during alcohol detoxification than participants receiving a standard American diet (Benzodiazepines are prescribed to reduce withdrawal symptoms during alcohol detox.)

The authors explained that, over the 3-week treatment period, the participants on the ketogenic diets showed lower “wanting” and increased reactivity to alcohol cues in the dorsal anterior cingulate cortex (dACC), compared with those consuming standard American fare. The ketogenic group also had altered dACC bioenergetics—specifically, elevated ketones and glutamate—and lower levels of neuroinflammatory markers. 

 

Food addiction and binge eating

 

Investigators in Italy conducted a small pilot study among five women to evaluate the ability of a very-low-calorie ketogenic diet (VLCKD) to reduce symptoms of binge eating and food addiction.

Rostanzo E, Marchetti M, Casini I, et al. Very-low-calorie ketogenic diet: a potential treatment for binge eating and food addiction symptoms in women. A pilot study. Int J Environ Res Public Health. 2021;18(23):12802.

 

In addition, the patients lost weight and fat mass. Weight loss ranged from 4.8% to 12.8% of each participant’s initial body weight. 

The study authors commented on their findings by noting that “food addiction and binge eating symptoms are associated with the consumption of high-glycemic foods rich in sugars, which are excluded in a VLCKD diet.”

Individuals following a ketogenic diet reported feeling slightly less hungry, fuller, or more satisfied. The mechanism of appetite suppression was not established, although there is evidence of a direct action of ketone bodies, along with modifications in the levels of hormones such as ghrelin and leptin, which influence appetite. The investigators believe that the VLCKD may be feasible to treat binge eating and food addiction.

“One of the most important goals for clinicians is to find an effective long-term dietary approach for people with food addiction and binge eating symptoms who wish to lose weight, ie, an approach that avoids weight regain and relapses,” they wrote.

 

The link between vitamin D, diabetes, and weight loss

 

Vitamin D synthesis in the human body is an important factor in overall health. A review in the journal Metabolites looked at studies examining the effect of ketogenic diets on vitamin D levels, and the subsequent effect on diabetes (and epilepsy).

Detopoulou P, Papadopoulou SK, Voulgaridou G, et al. Ketogenic diet and vitamin D metabolism: a review of evidence. Metabolites. 2022;12(12):1288.

 

 

According to the review authors, studies have shown that ketogenic diets lead to increases in circulating vitamin D. They also relate obesity to a vitamin D deficiency, which could partially explain the effect of ketogenic diets on weight loss.

“[V]itamin D concentration was inversely correlated with fat mass. In parallel, studies in adults prescribing a KD [ketogenic diet] mainly for weight loss mostly led to increases in circulating vitamin D," the authors wrote.

 

Neurologic conditions

 

Effects on neurologic conditions are the most studied area of ketogenic diets.

A comprehensive review in Nutrients looked at the many studies on the diet’s effects in neurologic conditions such as Alzheimer’s disease, epilepsy, migraines, multiple sclerosis, and Parkinson’s disease.

Dyńka D, Kowalcze K, Paziewska A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients. 2022;14(23):5003.

The large research base in these conditions allowed the authors to outline proposed physiological mechanisms for the beneficial effects, which are as follows: 

 

• Reduced production of reactive oxygen species

• Reduced neuronal inflammatory conditions

• Reconstruction of neuronal myelin sheaths

• Repair of damaged mitochondria and the formation of new mitochondria

• Provision of an alternative energy source for neurons in the form of ketone bodies

• Reduction in glucose and insulin concentrations

• Induction of autophagy

• Reduction of microglia stimulation

• Modulation of Intestinal microbiota and gene expression

• Assistance in the production of dopamine

• Increased conversion of glutamine into GABA

 

Cancer

 

 

A different review published in Nutrients assessed the role of the ketogenic diet in cancer.

Lane J, Brown NI, Williams S, et al. Ketogenic diet for cancer: critical assessment and research recommendations. Nutrients. 2021;13(10):3562.

The authors explain the theory behind its use and where it may fit in future cancer research.

 

The primary rationale for proposing a ketogenic diet as prevention or for treatment of cancer is to deprive cancer cells of their primary energy source, glucose.

This deprivation of glucose, the authors say, interrupts the elaborate processes of nutrient sensors and other factors that are activated in cancer cells by the presence of glucose and insulin. These processes appear to play important roles in cancer development and proliferation. 

With regard to future research, the authors believe it is unlikely that a ketogenic diet will cure cancer. Therefore, trials should focus on whether the ketogenic diet reduces cancer progression or recurrence in patients who experience remission through standard treatments.