Unexpected health effects of a ketogenic diet

Clinical Trials & Research

Ketogenic diets are diets that are high in fat and protein and very low in carbohydrates. This diet is meant to predominantly burn fats as an energy source. Research has shown that when the human body is experiencing energy restriction—a common occurrence with diets—human bodies tend to lower the amount of energy being used up by decreasing the resting metabolic rate (RMR).

Scientists use the term metabolic adaptation to describe this RMR decrease and a related decrease in energy being used. Resting metabolic rate is essentially the amount of energy needed for the human body to perform basic activities while it is resting, such as breathing and brain functions.

Below are some studies that investigated the health effects of a ketogenic diet. 

Long term effects on weight loss

Some ground-breaking research on ketogenic diets showed that extremely low-calorie ketogenic diets were capable of causing weight loss and assisting people in maintaining that weight loss for a period of up to two years. Researchers conducted this study because they wanted to test the hypothesis that very low-calorie ketogenic diets trigger a neutral reaction in terms of resting metabolic rate. They theorized that this would diminish the likelihood of body weight regain. Their intriguing results were published in the Nutrition & Metabolism journal.1

The low-calorie ketogenic diets the researchers had the obese patients follow did result in maintained weight loss, however, the diet did not lead to the expected RMR decrease. They suspect this neutral RMR reaction might have occurred because lean muscle mass is often preserved when following this diet.

The findings presented by these researchers demonstrated that a low-calorie diet was effective in maintaining normal resting metabolic levels, preserving lean muscle mass, and ultimately preventing metabolic adaptation—and perhaps weight regain for obese patients.

Ketogenic diet may not necessarily work long-term

To determine the better long-term weight loss rates, researchers from Iuliu Hatieganu University of Medicine and Pharmacy in Romania conducted a study of the ketogenic diet compared to a low glycemic index / nutrigenetic diet.2 Their results were published in the journal BMC Nutrition.

Patients in the ketogenic diet group ate no more than 35 grams of carbohydrates, no more than 10% total calories from fat, and protein intake between 1.2 g/kg bodyweight for women, and 1.5 g/kg bodyweight for men. 

Patients in the low-GI nutrigenetic diet group were DNA tested, and a diet plan was specifically developed based on the DNA testing. However, limits were placed on carbohydrates and saturated fat intake.

Both groups participated in 30-45 minutes of exercise per day, five days per week. During the first 24 weeks, body measurements were taken, and diet diaries were kept. Patients in the low-GI nutrigenetic diet also measured the amount of ketone bodies in their urine. After the initial 24 weeks, the patients were monitored for another 18 months to determine the long-term effects of the diets.

After the first 24 weeks, the ketogenic diet group lost more weight than the low-GI nutrigenetic diet. However, after 18 months, the ketogenic diet group gained more weight back than the low-GI nutrigenetic group. 

Study results suggest that while the ketogenic diet is better for weight loss initially, in the long term sustained weight loss and health benefits are better using a low-GI nutrigenetic diet. 

How ketogenic diets affected skin inflammation

Psoriasis is marked by inflammation. Inflammation of the skin, of nearby joints, known as psoriatic arthritis, even of the blood vessel occurs higher in psoriasis sufferers. Recent research has shown that diet plays a key role in controlling inflammation. Ketogenic diets have been shown to have anti-inflammatory properties and may provide some relief for skin inflammation.

Researchers from Paracelsus Medical University, Salzburg, Austria performed a study to determine does a ketogenic diet reduce skin inflammation. Their results were published in the Journal of Investigative Dermatology.3

During the study, mice were fed different diets. The diet types were a standard diet, a ketogenic diet full of long-chain triglycerides, a ketogenic diet full of long and medium-chain triglycerides, and these three diet types supplemented with omega-3 fatty acids. Omega-3 fatty acids and medium-chain triglycerides are thought to provide anti-inflammatory benefits.

Medium-chain triglycerides are found in coconut oil, palm kernel oil, milk, and cheese. Long-chain triglycerides are found in soybean and safflower oils.

When compared with mice on a non-ketogenic diet, the ketogenic diet with high medium-chain triglycerides aggravated the symptoms of psoriasis in mice. Ketogenic diets that mainly contained long-chain triglycerides did not worsen the psoriasis. The researchers did not confirm that a ketogenic diet reduces skin inflammation.

In a press release study co-lead, Dr. Barbara Kofler said, “We found that a well-balanced ketogenic diet, limited primarily to long-chain triglycerides (LCTs) like olive oil, soybean oil, fish, nuts, avocado, and meats, does not exacerbate skin inflammation. However, ketogenic diets containing high amounts of MCTs especially in combination with omega-3 fatty acids, should be used with caution since they may aggravate pre-existing skin inflammatory conditions.”

Ketogenic diet and epilepsy 

The gut microbiota is an essential component for human health, and diet is an important factor for determining the composition of the gut microbiota. The gut microbiota is involved in metabolic and neurological pathways, so it is possible that the ketogenic diet alters the gut microbiota in a way that alters these pathways to treat epilepsy.

In a study published in Cell,4 the authors were interested in determining how the ketogenic diet alters the gut microbiota, and if this change in the gut microbiota mediates the anti-seizure effects. The authors used a mouse model of refractory epilepsy, a type of epilepsy where medicine is not able to control seizures, to investigate the mechanism that the ketogenic diet prevents seizures.

First, the authors showed that, in only four days, the ketogenic diet altered the gut microbiota by increasing abundance of the bacterial species Akkermansia muciniphilaand Parabecteroides. Then, the authors demonstrated that the ketogenic diet increased the seizure threshold of the mice after electrical stimulation, but when the mice were treated with antibiotics that diminish gut microbiota, the seizure threshold to electrical stimulation returned to control levels. Further, in mice lacking gut microbiota all together, the ketogenic diet had no effect on seizure threshold.

The researchers went on to see if they could identify which bacterial species were important for seizure protection. In antibiotic-treated mice, the addition of Akkermansia muciniphila and Parabecteroidesbacterial species together could restore the increased seizure threshold seen in mice fed the ketogenic diet.

In mice fed a normal diet, the addition of Akkermansia muciniphila and Parabecteroidesbacterial species provided some protection against seizures, demonstrating that these bacterial species are important in mediating the therapeutic effect of the ketogenic diet, rather than carbohydrate restriction and ketone production.

Researchers also tested a mouse model of temporal lobe epilepsy and saw the same results, demonstrating that gut microbiota can improve seizures of different types of epilepsy.

Scientists are continuing to learn about the critical role gut microbiota plays on human health. Here, researchers determined that the ketogenic diet alters the gut microbiota to produce antiepileptic effects. Further research is required to determine whether some cases of epilepsy are due to altered gut microbiota, and if microbe-based therapeutics can be effectively and safely used.

Always consult your doctor before making any changes to your diet.

References:

1. Canton, A., Ordoñez-Mayan, L., … Casanueva, F. F. (2018). Resting metabolic rate of obese patients under very low calorie ketogenic diet. Nutrition & Metabolism15(1), 18. https://doi.org/10.1186/s12986-018-0249-z

2. Vranceanu M, Pickering C, Filip L et al. A comparison of a ketogenic diet with a LowGI/nutrigenetic diet over 6 months for weight loss and 18-month follow-up. BMC Nutr.2020;6(1). doi:10.1186/s40795-020-00370-7 

3. Locker F, Leitner J, Aminzadeh-Gohari S et al. The Influence of Ketogenic Diets on Psoriasiform-Like Skin Inflammation. Journal of Investigative Dermatology. 2019. doi:10.1016/j.jid.2019.07.718

4. Olsen, C.A., Vuong, H.E. Yano, J.M., Liang, Q.Y., Nusbaum, D.J. & Hsiao, E.Y. (2018). The gut microbiota mediates the anti-seizure effects of ketogenic diet. Cell173, 1728-1741.

Image by healthguru from Pixabay 

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