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Ketogenic Diets: An Objective Look at the Research

Nina Ghamrawi, MS, RD, CDE
August 25, 2023
August 26, 2023

Clinically approved recommendations for daily carbohydrate intake is around 45-65% of calories from carbohydrate. Low carbohydrate diets typically tend to be limited to around 25% grams carbohydrate per day, but ketogenic diets can drop carb intake as low as 5-6%, replacing the lost carbohydrates with fat. This has been highly controversial for many reasons, but still very trendy because it shows results. If you want some of the detailed research behind keto, here's the skinny.

There are usually 25-30g or less of carbohydrates per day, or around 5-6% of a 2000 calorie diet. In place of carbohydrates, the diet in turn becomes around 60-75% fat and 20-35% protein.

The Good:

Potential benefits for certain types of epileptic conditions

If you want to know about ketogenic diets and the brain, look at the part of the brain known as the hippocampus - this part is responsible for learning and memory, but also a type of epilepsy called mesial temporal lobe epilepsy. There is some research to suggest a low carb diet helps treat epileptic seizures in the brain by breaking down mutated mitocholndrial DNA in the brain. One study suggests that among neurological disorders with mitochondrial dysfunction, patients should avoid a ketogenic diet because it may accelerate rather than reverse the neurodegenerative process. From this research, a ketogenic diet may act as a stressor (just as exercise would) with potentially beneficial effects on the brain which promotes the  natural selection of healthy mitochondria, but in those individuals with mutated DNA, the diet requires further testing. Other research on neurological diseases like Alzheimers and Parkinson's disease suggests also a potential temporary benefit. The evidence is not clear enough to support use of the diet for those individuals, and more research is needed.

Keto: Long-Term

There aren't many longitudinal studies regarding people on keto diets for a long-term, but this one publication from Virta has research after 1-year of patients being on the program. There have been significant reductions in weight, and they decreased or discontinued some patients’ hypertension and diabetes oral medications on this diet after just one year. Part of the reason patients remain stable at the end of year one is simply because weight reduction is directly linked to improvements in blood pressure and diabetes. A lot safety issues need to be addressed in their long term trial, but I look forward to their 2-year data on these same subjects.

Improved short-term weight and glucose control

For many individuals, a ketogenic diet has been shown to improve their weight over time, thus improving glucose control.  Also because the diet is extremely low carbohydrate, Diabetic patients see a significant improvement in average plasma glucose and A1C. For Diabetics, this seems like a dream come true, right?

The Bad: 

Fatty Liver Disease and High Cholesterol

Although ketogenic diet intervention is effective in reducing body weight and controlling glucose homeostasis, it caused lipid metabolic disorders after just 6 weeks on the diet. Specifically, liver function tests, total cholesterol and free fatty acids in the blood rose, and rose more significantly in those with Diabetes. When combined with moderately intense cardiac exercise 5 days per week, however, these negative effects on the liver and cholesterol were muted.

Given the potential for increased use of dietary protein and protein from the  muscles for energy, the breakdown of these proteins may potentially lead to increased work by the kidneys to excrete excess nitrogen. Those with renal insufficiency, as a result, may suffer more from a high fat diet, though a couple studies have shown that a ketogenic diet may actually reverse diabetic nephropathy.

Effects on Digestion, Heart Health, and Liver

Those individuals with gastroesophageal reflux (GERD), heartburn, or problems with inborn errors of fat metabolism should not be on this diet. Diabetic patients taking SGLT2 inhibitors (Canagliflozin/Invokana, Dapagliflozin/Farxiga, Empagliflozin/Jardiance, or Ertugliflozin/Steglatro) should also not be on this diet. The diet is also extremely difficult to digest, and since it can stress the liver and other aspects of fat metabolism, it is not recommended for people with a poor appetite, or those with fatty liver, cirrhosis, cardiomyopathy, or dyslipidemia (non-normal cholesterol levels).

Weight Loss Is NOT Guaranteed

So if you think that you can go on a high fat diet and actually reduce your body fat, you're only getting part of the research. A few studies show many groups of individuals, especially those with a systemic nervous system that isn't completely intact, or patients who (aside from diabetes) are not completely healthy, a ketogenic diet may not help at all. On the contrary, most subjects in this study showed similar or better ketosis buildup with a diet of lower fat content. These observations suggest that personalized monitoring, and regular blood work before and during diet initiation is necessary Also, patients with an already with lower fat percentage, BMI, as well as higher metabolic rate (REE) have higher ketone buildups, and thus already metabolize fat more efficiently and thus would see more of a benefit than those with a slower metabolism.

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