11 Ketogenic Diet for Weight Loss Studies Reviewed; News from Harvard on the Horizon

Kiah Connolly, MD
     
Kiah Connolly, MD

Whether it’s with uncontained enthusiasm or harsh criticism, it’s hard to avoid hearing something somewhere about the new Keto-Craze.

So is keto the key to weight loss we’ve been missing all these years?

Or is it a dangerous fad that we should be warning our friends and family about?

The truth is, the answer is probably not going to be found on either end of these extremes. With any new hype involving such polarizing opinions, it’s always important to go back to the books and look at what the science says.

This article includes a summary of  peer-reviewed clinical studies to date, a promising new study in the works, and future research involving the keto diet for health and weight loss.

Looking for a comprehensive overview on all things keto? Read this article: The Keto Diet Explained by a Doctor and Dietitian.

 

Keto Diet Studies for Weight Loss


Why is losing weight and keeping it off so darn difficult?

While almost any diet can be successful if done properly, there has been literature suggesting that a low carbohydrate diet may provide superior benefits for weight loss (1). Indeed, the ketogenic diet does encompass a low carbohydrate diet.

But is there anything that makes the ketosis approach unique from other low carbohydrate diets?

Well, it turns out our bodies are hard wired from back in the ‘caveman days’ to ensure we’re getting enough nutrients. So, when we start losing weight, various hormones are released to make us really hungry and to encourage our body to decreases our overall energy to conserve what we have. If you’ve ever been on a diet you can probably attest to feeling more fatigued and hungry!

Can ketosis provide a way around this? Theories and some early studies suggest that when a state of ketosis is achieved, the signals in your body to increase hunger and decrease energy are suspended - ideally leaving you energetic, satiated and thus more capable of sticking to your diet (2).

There are many well done studies showing how the ketogenic diet can successfully treat seizures (3). These studies and others suggest that the ketogenic diet is safe for children with epilepsy and for individuals utilizing it for weight loss (4, 5).

However, the manner and extent to which ketosis may benefit other health conditions including how ketosis may independently accelerate weight loss beyond the well accepted calorie control paradigm has thus-far largely been based on theories (6). Unlike the plethora of positive data on ketosis for seizures, there are very few clinical studies that look directly at its independent effect on weight loss.  

Below includes a summary of the science that exists thusfar evaluating the keto diet for weight loss. All of the studies included are peer-reviewed and on human participants.  

Bottom Line: From the little evidence that exists, there seems there may be a positive effect of the ketogenic diet on weight loss. However, more research is needed to determine if ketosis is uniquely beneficial for shedding unwanted pounds.

 

Is Ketosis an Appetite Suppressant?

 

 

Boy on temptation with burger

 

Some people believe that being in a state of ketosis can actually suppress your appetite.  So how exactly could this diet affect your hunger and satiety?

The Hunger Hormone 

A special substance in your body called 'ghrelin' is often referred to as ‘the hunger hormone’ and has therefore been of particular interest in this debate. Your body traditionally increases ghrelin in order to stimulate your appetite. Some theories suggest ketosis may decrease your appetite by suppressing a rise in ghrelin. 

Let's see what the studies so far say. 

 

1) Gibson, AA et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. 

This meta-analysis looked at all of the peer reviewed published studies on the effect of the ketogenic diet on appetite suppression in people.

Study Details: 

12 studies were found to involve people on a ketogenic diet subjectively rating their appetites. Some of these studies were randomized while others were not. However, all participants rated in each of these studies were confirmed to be in a state of  ketosis.

Study Results: 

When looking at the individual studies, only 4 were found to have a significant increase in fullness/satiety and non found a significant decrease in hunger. However when combining the data from all of the smaller studies together into what is considered a meta-analysis, there was a significant increase in fullness/satiety and decrease in hunger. Nine studies were not included in the meta-analysis due to different data formats utilized. Of these studies, 2 reported a decrease in hunger and 5 reported no significant change, and 2 of these studies reported increased hunger while on the ketogenic diet.

 

Forest Plot Satiety Ketosis

Discussion: This information provides a mixed picture, showing that it’s not yet clear if ketogenic diets can effectively suppress appetite. As many of these studies have conflicting results, more research is needed to elucidate the effects of ketosis on hunger.


 

2) Sumithran, P et al. Ketosis and appetite mediating nutrients and hormones after weight loss. 

 

Study Details: 

39 people completed this study which involved 8 weeks of a ketogenic very low carbohydrate diet and subsequently 2 weeks of a balanced diet. Both subjective levels of appetite and objective levels of hormones including  glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones were measured.

Study Results: 

While on the ketogenic diet, people had increased levels of b-hydroxybutyrate (marker of ketosis) and levels of ghrelin were suppressed. On the balanced diet the markers of b-hydroxybutyrate was not elevated and ghrelin levels were elevated. Glucose, amylin, leptin, and subjective measures of appetite were lower in the ketogenic diet compared to the balanced diet.

 

ketosis and appetitie-mediating nutrients and hormones after weight loss

Discussion: This small study supports the theory that ketosis may suppress both ghrelin and appetites. 

 

3) Johnstone, AM et al. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum.  

 

Study Details: 

17 men completed a residential cross-over study in which they each ate 4 weeks of a low carbohydrate ketogenic diet and 4 weeks of a medium carbohydrate non-ketogenic diet. 

Study Results: 

Hunger was significantly lower and weight loss was significantly greater when patients were eating a low carbohydrate ketogenic diet compared to a medium carbohydrate non-ketogenic diet. 

Discussion:  It's important to be careful when interpretting this study, as with many others it is very small and may incorporate many elements of bias. However, it's conclusions support the theory that ketosis may blunt hunger and could be a superior diet for weight loss.

 

Ketogenic Diet vs. Low-Fat Diets

 

Many studies support a low-carbohydrate diet may be superior to low fat diets. But what research involves comparing the ketogenic diet to low-fat diet?

This meta-analysis did a lot of literature review for us. It looked at all of the randomized controlled trials published on evaluating weight loss in very low carbohydrate ketogenic diets and low fat diet studies prior to its publication in 2013.

 

4) Bueno, NB et al. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trial. 

 

Study Details:

These authors found the 13 studies (randomized controlled trials) that had been done to date of patients on a Very Low Carbohydrate Ketogenic Diet (VLCKD) or a Low Fat Diet (LFD) and had a follow up evaluation of their participants in at least one year. The studies primarily looked at bodyweight. However they also measured other health measures including cholesterol, blood pressure and glucose.

Study Results: People in the ketogenic diet group lost significantly more weight and had lower blood pressure than patients in the low fat diet group.

 

Discussion:

These studies suggest that a keto diet seems to be superior to a low fat diet  for weight loss and potentially other cardiovascular risk factors such as blood pressure. While these studies provide additional support for a benefit of low carbohydrate diets over low fat diets, they do not evaluate if ketosis offers any unique benefit over other low carbohydrate diets. 

 

Ketogenic Diet vs. Low Calorie Diets

 

Much debate exists on whether all calories are created equally when it comes to weight management. Do macronutrients matter when losing weight?   

 

5) Partsalaki I, et. al. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents. 

 

Study Details:  

58 obese children were assigned to either a low calorie diet or a ketogenic diet for 6 months. 

Study Results: While both groups significantly decreased their weight, waist circumference and fasting insulin, the ketogenic group seemed to produce greater positive results. 

 

Discussion:

The ketogenic diet may be superior to low-calorie diet in obese children. 

 

6) Moreno, B et. al. Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. 

 

Study Details:

A group of individuals were randomized to either very low-calorie-ketogenic diet (VLCK) or very low-calorie diet (LC). Both groups received similar external support including counselling on physical activity. Weight loss was evaluated at 2 months and 12 months. 

Study Results: 

At 2 months, the weight reductions in the VLCK diet and LC diet groups were 13.6 ± 3.9 and 4.8 ± 2.7 kg, respectively (p < 0.0001). At 12 months, the weight reductions were 19.9 ± 12.3 and 7.0 ± 5.6 kg, respectively (p < 0.0001).

Discussion: The very low-calorie-ketogenic diet led to significantly greater weight loss than a traditional low-calorie diet when evaluated at 2 and 12 months. 

 

Ketogenic Diet for Longterm Weight Loss

 

Can keto be a long term solution for weight loss? Theoretically, yes. But there are so many ways one can go about involving ketosis in keeping weight off.

Is a perminant state of ketosis the most effective way to stay fit?

Or can intermittent periods of ketosis among an otherwise balanced diet be just as or even more effective than persistent sustained ketosis?

 

7) Paoli, A et al. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol.

Study Details:

89 people participated in a 12 month study in a preplanned cyclic diet scheme that involved a 20 day ketogenic phase, 20 days low carb-non ketogenic phase; 4 months Mediterranean normocaloric nutrition phase; followed by a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. 

Study Results:

Most people (85%) in the study demonstrated significant sustained weight loss. Furthermore there were also significant improved health markers including decreased total cholesterol, LDLc, triglycerides and glucose.

 

weight loss on a ketogenic diet

 

Discussion: People in the study enjoyed successful weight loss and improvement in cardiovascular markers by alternating between ketosis and a balanced diet. However it's important to note that this did not evaluate whether intermittent ketosis is more or less effective than sustained ketosis or other non-ketotic diets. 

 

8) Moreno, B et al. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burdern of disease.  

Study Details:

This study focused on the long term affects of a very low-calorie-ketogenic diet on long term weight loss. Over the course of two years, this study compared the efficacy of 45 obese individuals on a ketogenic diet to 23 obese individuals on a low-calorie diet. 

Study Results:

The very low-calorie-ketogenic diet induced a greater reduction in body weight (−12.5 kg), waist circumference (−11.6 cm), and body fat mass (−8.8 kg) than the low-calorie diet (−4.4 kg, −4.1 cm, and −3.8 kg, respectively; p < 0.001). 

Discussion: The very low-calorie-ketogenic diet was more effective for weight loss than a traditional very low-calorie diet over a two year period. 

 

Ketogenic Diet & Diabetes

 

ketogenic diet and diabetes

People with diabetes may uniquely benefit from the ketogenic diet in a variety of ways. Because the nature of diabetes involves an inability to process carbohydrates appropriately due to inadequate insulin function, it makes sense that decreasing the number of carbohydrates consumed may be beneficial for the disease. Additional studies demonstrate ketosis improves insulin function and therefore could have additional significant positive effect on these individuals (7). 

Many studies support that a low carbohydrate diet may be superior to a low-fat diet in patients with diabetes (8). While there are few studies looking at a ketogenic diet for patients with diabetes, the results thus-far seem promising. 

 

 9) Hussain, T et al. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. 

 

Study Details:

363 adult patients ate either a low calorie diet or a low carbohydrate ketogenic diet for 6 months and completed a 24 week follow up evaluation. Body weight and various chronic disease markers were evaluated between those who were diabetic and those who were not diabetic in each diet group compared. 

Study Results:

While both diets led to improvements in body weight and chronic disease markers, these effects seemed to be more substantial in the low carbohydrate ketogenic diet group including a significantly greater improvement in HbA1c in the ketogenic group compared to the low calorie group. 

 

ketodiet and weight loss in diabetes

ketogenic diet and diabetes

Discussion:  A low carbohydrate ketogenic diet may be superior to a low calorie diet alone for patients with diabetes.   

 

10) Goday, A et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. 

 

Study Details:

89 adults with diabetes were randomized to either a low calorie diet or a ketogenic diet for a duration of 4 months. 

Study Results:

Weight loss, reduction in waist circumference and HbA1c was significantly greater in the ketogenic diet than in the low calorie diet.

Discussion: This study supports that the ketogenic diet is superior to a low-calorie diet in improving glycemic control and weight loss in people with diabetes. 

VLCK ketogenic diet

 

Is the Ketogenic Diet Good for Your Health?

 

Some people are concerned that very low carbohydrate and high fat diets may be bad for the body by increasing the risk factors for cardiovascular disease. This study compared weight loss and many of these risk factors between very low carbohydrate diets and calorie restricted diets. 

 

11) Brehm, BJ et al. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. 

 

Study Details:

Randomized controlled trial of 53 individuals to a very low carbohydrate diet or a calorie restricted diet for 6 months. Calorie in take was similar between both groups.

Study Results:

Participants in the very low carbohydrate diet lost significantly more weight and more body fat than the calorie restricted diet alone. At 6 months factors contributing to cardiovascular disease including blood pressure, glucose, lipids and insulin all improved in both groups equally. B-hydroxyburate levels were increased in the very low carbohydrate group.

 

body fat in a ketogenic diet

Discussion: While fairly small, this study provides support that a very low carbohydrate diet may have a greater impact on weight loss than calorie control alone. It also supports that this diet is safe and suggests the keto diet may improve cardiovascular risk factors.

 

Harvard’s Keto Diet Plan in the Works  


As explained above, the theory that ketosis independently supports weight loss and also ‘tricks’ your body into not being as hungry has been evaluated by very few small studies.

Dr. Ludwig et al at Harvard University is amidst the largest and arguably most well controlled study evaluating the effect of the ketogenic diet on weight loss and health (9). He is working with 125 adult participants with obesity who will be living in a residential facility for 13 weeks during which time their diets will be strictly controlled. Participants will be randomly assigned to one of three groups where they will be exclusively eating either a very low carbohydrate (ketogenic) diet fueled by food from Trifecta, DASH low sugar diet or DASH high sugar diet.

Trifecta salmon in package and on plate

Not only will this study be comparing these three diets for weight loss efficacy in a highly controlled environment, but it will also be evaluating the effect of different quantities and types of carbohydrates on health and weight loss. Furthermore, they will also be comparing the effects each diet has on other cardiovascular risk factors, such as lipid profiles and insulin sensitivity.

As DASH (Dietary Approach to Stop Hypertension) is currently one of the most well accepted diets among the medical community for obesity and other cardiovascular risk factors, results from this study have the potential to challenge current nutritional dogma if the keto diet is found to be superior.

 

Future Research for Ketogenic Diet

Despite the high anticipations many hold for the results of this study, it may be just the beginning of work needed to evaluate the potential power of keto. Well done studies evaluating the potential difference between traditional low carb diets and the very low carbohydrate ketogenic diet have yet to be performed. And while this ongoing Harvard study is the largest and most well controlled on the ketogenic diet to date, even more research and more participants are needed to provide enough data needed to change recommendations for health and wellness.

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