A Review of the Ketogenic Diet

An effective way to lose weight safely

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Backed by Science: the Keto diet works

The Keto diet is based on a very low carbohydrate, moderate protein and high fat intake. This nutrient combination shifts the body from using glucose as its fuel to burning fats. This creates ketones which provide the body with energy. Fat is metabolized causing weight loss and ketones inhibit appetite.

It improves Body Mass Index (BMI) and reduces total cholesterol, triglycerides and blood sugars; it improves HDL cholesterol too.

It may have neurological protective effects for conditions such as Alzheimer's, Parkinson's disease, some tumors, ALS and even acne.

Below we will review the Keto Diet based on scientific studies.

Sugar, Fats and our Body's energy

The Normal energy source: Glucose

Avoid low quality carbohydrates: sugars, starches, flour.

The body generates the energy it needs inside its cells, in a process that is called "Cellular Respiration". The basic fuel is glucose, a six-carbon form of sugar, which is a carbohydrate.

Respiration is quite a complex process that takes place in a series of steps which are the following (we have simplified some of the intermediate chemical reactions):

1. Glycolisis

The name combines the Greek words "glykys" = "sweet" and "lysis" = "splitting", meaning: "sugar splitting", and that is precisely what takes place inside the cells' cytoplasms.

Sugar in the form of glucose (a six-carbon chain) is broken down into two shorter sugar molecules containing 3 carbon atoms each called pyruvate or pyruvic acid.

This splitting process requires an initial energy input which is provided by a molecule known as adenosine triphosphate or ATP.

Glycolisis generates energy in the form of more ATP molecules and the pyruvic acid it produces enters the second step of respiration:

2. Production of Acetyl CoA

The pyruvic acid enters small organelles located inside the cell, known as mitochondria. They are the "cell's powerhouse" and generate its energy.

Once inside a mithocondrion, pyruvic acid is converted into a shorter 2-carbon sugar called acetyl coenzyme A (or Acetyl CoA) and one molecule of CO2 (Carbon dioxide).

Krebs Cycle

Acetyl CoA enters a process known as the citric acid cycle, TCA cycle or Krebs cycle. It is oxidized (that is why we need to breathe: to provide oxygen for the Krebs Cycle), and produces more CO2, some ATP and hydrogen atoms.

In the final stage of respiration, known as "Electron Transport System" the hydrogen atoms react with even more oxygen to produce water and a large amount of energy which is stored as ATP.

The overall reaction can be summarized as follows:

Glucose + 6 O2 → 6 CO2 + 6 H2O + 36 ATPs

ATP cycle and the Keto Diet

During a ketogenic diet, the body will tap its glucose stores, and when these run dry, it resorts to its stores of Glycogen.

Glycogen and weight loss

Glycogen is a variety of sugar made up from glucose residues that is stored in the muscles and liver (10% of liver weight is glycogen, as is 2% of skeletal muscle weight).

Glycogen is metabolized following the same route as glucose and in the process 1 g of glycogen produces 3 g of water, which is eliminated in the urine. (MacKay, 1932)( 1 )

An average man weighing 200 lbs, with a normal muscle mass of 35% and a 3.5 lb liver would therefore store: 4 lbs of glycogen in muscle tissue and 0.35 lbs in the liver, which would result in 13.05 lbs of water bound to it.

Burning these glycogen stores result in a weight loss of 17.4 lbs of water and burned sugars.

The use of glycogen before the onset of ketosis is the reason for the sudden loss of weight experienced during the first stages of a keto diet.

After using up the glycogen, the body needs more fuel to keep up with the cells' energy requirements, so it turns to its fat stores. And ketosis begins.

Burning Fat

Fat molecules known as triglycerides are the fuel that the body burns during ketosis.

Triglycerides

Their name indicates that they have three fatty acid chains linked to a glycerol molecule. These triglycerides enter the mithocondrion and are broken down to produce acetyl-CoA which then enter the Krebs Cycle to generate energy as we explained above. This process is known as β-oxidation.

Disrupting the Cycle

However, during special circumstances such as fasting, starvation, keto diet or after vigorous exercise, and in cases of non-controlled type 1 diabetes, the mitochondria in the liver alter their Krebs cycle.

They do so because a molecule that is critical for the cycle, known as oxaloacetate, is used for another purpose: production of glucose.

Insulin and sugars during ketosis

As carbohydrate intake is very low (between 20 and 50 g daily), insulin secretion decreases, and this reduces the signal that instructs the cells to store fat and glucose. Instead of being stored, they are consumed.

But the body needs sugar and can -and does- produce it in the liver: this is a proces known as "Gluconeogenesis", by which glucose is generated from non-carbohydrate moleucules such as glucogenic amino acids from proteins or glycerol from fats (the liver breaks down triglycerides).

The amino acid source gradually decreases as the days go by and is replaced by triglycerides and this effect is more noticeable in obese people, who generate up to 80% of their glucose by burning fat (Bortz, 1972) ( 2 ) while lean subjects burn more "protein" than fats (only 38% of their glucose comes from fats).

The liver releases this glucose into the bloodstream.

Ketone bodies

As oxaloacetate levels are low, little acetyl-CoA enter the Krebs cycle. Instead it is diverted into the formation of "ketone bodies", which aren't bodies at all, they are water soluble molecules known as ketones.

They come in three varieties:

  • acetoacetate
  • beta-hydroxybutyrate (β-hydroxybutyrate) or BHB
  • acetone

The liver releases these ketone bodies into the bloodstream, which distributes it to the body's cells. Their mitochondria can convert the ketone bodies back into acetyl-CoA, and feed it into their Krebs cycle to generate energy.

Ketone bodies can also enter the cells of the central nervous system (fat cannot cross the blood-brain-barrier, but ketones can), and provide them with a source of fuel when glucose is short.

Ketosis

Ketones in the blood cause a condition known as ketosis, Vargas (2018) ( 3 ) shows that β-hydroxybutyrate which in non-fasting or non-keto-dieting individuals is less than 3 mmol per liter, increases to around 7-8 mmol ⁄ L during a keto diet, yet this does not alter the blood pH (ketones are acidic).

Ketosis is not the same as ketoacidosis

The keto diet induces a state of physiological ketosis which is not the same as the diabetic ketoacidosis (where ketones in blood can reach concentrations of 20 mmol ⁄ L and acidify the blood of diabetic subjects).

Ketoacidosis is dangerous in diabetic subjects as it can cause coma and even death.

Acetoacetate like most ketones has a typical characteristic sweet and fruity smell. Its odor can be detected in the urine during ketosis. Acetone generated spontaneously from acetoacetate is a toxic byproduct which evaporates easily and is eliminated during respiration, giving a fruity odor to the breath (which, by the way, is a sign that the subject is in ketosis).

About 10 or 20% of ketone bodies are lost in the urine.

Ketosis can be defined as a metabolic state characterized by increased quantities of ketone bodies in the body tissues.

What is a Ketogenic Diet?

Ketogenic: definition

Ketogenic means "generator of Ketones", and that is the basis of the diet: generate ketone bodies through a restriction in the intake of carbs and an adequate input of protein and fats.

Masood and Uppaluri (2018) ( 4 ) give a detailed scientific review of the ketogenic diet (KD for short). They define it asa high-fats, moderate-proteins and very-low carbohydrates diet.

The breakdown of calories and quantities of these macronutrients are generally the following:

These values are known as Macros:

  • Carbohydrates: 20 - 50 g per day (5 - 10% of daily calorie needs).
  • Fats: 55 - 60% of total daily calories
  • Protein: 30 - 35% of daily caloric intake

The moderate protein intake is to prevent the body from making glucose using protein as a raw material (the process known as gluconeogenesis which we described further up). The idea is to supply the necessary amino acids but not more than that.

Based on this, and knowing your daily energy requirements you can calculate your "macros" for a Keto Diet tailored to your body and needs:

Read More about our Keto Macros Calculator:

> > Keto Diet Calculator

Compare the ketogenic diet macros with those of a typical American diet:

The Typical American Diet

The average American diet is based mainly on carbohydrates (55% of the daily caloric intake): 200 to 350 g ⁄ day.

A large proportion of refined carbs (sugars and starches) promotes obesity and increases the risks of diabetes and metabolic syndrome.

Low quality carbohydrates don't leave room for healthy carb options such as nuts, unprocessed grains, vegetables or fruits.

Origin and History of the Keto Diet

It was created by Russel Wilder in 1921, he used it to treat seizures in epileptic children in time when antiepileptic drugs were unknown. Most studies of long-term effects of ketosis were therefore conducted on children.

Its use for dieting and weight loss is a relatively modern concept.

High Fats for dieting?

The general consensus for many years has been that consuming less fat and replacing it with carbohydrates leads to weight loss.

However the Ketogenic diet proposes the opposite: drastically cutting back on carbs and increasing consumption of fats.

Paoli (2014) ( 5 ) points out that the low fat approach, which is the most commonly accepted dietary strategy "yield only modest weight losses and suffer from low long-term compliance issues"; this is due to two factors:

  • Obese people prefer foods that are rich in fat, which are restricted in conventional diets, and
  • When they select carbs they choose highly processed foods made up of refined sugars rather than complex or raw carbs, worsening weight issues
Natural olive oil.
Oregon State University

A low carb and high fat diet (i.e. a ketogenic diet) avoids both problems.

Bear in mind that fats does not necessarily mean lard or grease. There are many healthy options that allow you to include fats into your diet such as olive oil or canola oil.

Conventional wisdom states that high-fat diets can cause heart disease, diabetes and obesity but this has not been observed in scientific studies: "Studies carried out in animals that were fed high-fat diets did not show a specific causal relationship between dietary fat and obesity. On the contrary, very-low-carbohydrate and high-fat diets such as the ketogenic diet have shown to beneficial to weight loss" (4).

Diet Length

Masood & Uppaluri (2018) (4) recommend following it for a period not shorter than 2 or 3 weeks and not longer than 6 to 12 months. And emphasize that kidney funcitions must be monitored while on a KD and that the transition out of a ketogenic diet to a normal one should be gradual and well controlled.

Take home point

If you have renal issues, don't follow a ketogenic diet.

Let's look into its pros and beneficial effects in the following section:

The Ketogenic Diet helps to lose weight

Masood and Uppaluri (2018) (4) cite several studies that compared the long-term effects of diets (such as maintaining weight loss vs. recovering the lost fat after finishing the diet) which found that "low-carbohydrate diets led to significantly greater weight loss compared to low-fat interventions".

They also found that the quality of calories consumed affects the quantity of calories burned. It is good for the body to maintain its Basal Metabolic Rate, and that is what happens during a keto diet. Low fat diets on the other hand cause BMR to drop considerably, which is not desireable as the body will burn less energy in response to its lower caloric intake.

Learn more about Basal Metabolic Rate and how to calculate it.

Weight Loss

The initial weight loss during a ketogenic diet is up to 10 lbs in 2 weeks or less.

This loss is due to the diuretic effect of the diet as mentioned further up when we discussed the water lost due to the breakdown of glycogen.

The intake of protein ensures that muscle mass is not lost.

Paoli (2014) (5) sumarizes the possible ways that a ketogenic diet causes weight loss:

  • Less production of fats (reduced insulin causes less cellular uptake of fats). Increased lipolysis (fats breakdown for use as fuel).
  • The extra energy burned by the body to generate glucose by gluconeogensis: making sugar from protein or fats requires around 400 to 600 Calories ⁄ day. It is an "expensive" way to obtain sugar. This extra energy requirement contributes to weight loss.

Take home point

A ketogenic diet is effective in causing weight loss.

Another weight loss mechanism of KD is its ability to decrease hunger:

The Keto diet suppresses appetite

A meta-analysis by Gibson et al., (2015) ( 6 ) found that individuals following a Ketogenic low-carbohydrate diet "were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people.".

Take home point

A ketogenic diet prevents an an increase in appetite, makking you feel slightly less hungry (or more full or satisfied).

Paoli (2014) (5) adds that the reduced appetite may be also due to the effect of proteins which cause greater satiety or to its effect on the hormones that control appetite (such as ghrelin).

Masood and Uppaluri (2018) (4) confirm that ketosis causes hunger pangs to subside.

The Keto Diet is better than a "low fat" diet

Brehm (2003) ( 7 ), in a trial involving 53 healthy obese women (BMI of 33.6 on average). They all received a low calorie diet during a 6 month period, but half went on a very low carbohydrate diet and the other half followed a low fat diet.

The outcome was that the very low carb group lost more weight 18.7 lbs. vs. 8.6 lbs. and and more body fat (10.6 lbs. vs. 4.4 lbs.) than the low fat diet group.

The study concluded that "a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on important cardiovascular risk factors in healthy women".

More Positive effects of Ketogenic Diets

We have separately reviewed the negative aspects of a keto diet in our "Negative Aspects of a Keto Diet" webpage, so here we will go over its positive aspects.

A review of different scientific papers by Paoli et al., (2013) ( 8 ) indicates that there is "emerging evidence" of the benefits of a ketogenic diet in treating not only obesity, but also "pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors".

Let's look into some detailed benefits of a ketogenic diet:

Cardiovascular Disease and Blood lipids

Dasthi et al., (2004) ( 9 ) studied 83 obese subjects with a BMI (Body Mass Index) greater than 35 -meaning that they were very obese. Thse individuals followed a keto diet during 24-weeks with the following macros:

  • 30 g carbohydrate
  • 1 g/kg body weight protein
  • Fats were distributed as follows: 20% saturated fat, and 80% polyunsaturated and monounsaturated fat.

Learn more about Macros on our Keto Diet Calculator webpage.

All subjects lost weight and BMI. And they also improved all key indicators: total cholesterol (drop), HDL (increased), LDL (decrease), Triglycerides (drop), sugar (drop).

Dashti concluded that their "study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated." (a six-month diet).

Masood and Uppaluri (2018) (4) mention a series of improvements that overweight subjects will notice after following a keto diet:

  • Glucose control improves, so does insulin sensitivity
  • Improved blood pressure
  • Lower blood lipids (triglycerides)
  • Higher good cholesterol (HDL).

However "bad" cholesterol LDL may increase on a KD

Take home point

A KD improves HDL, BMI, Total Cholesterol, Triglycerides and fasting glucose levels. Watch out for LDL though!

nurse holding a paper heart
Look after your heart

Keto Diet Reduces Fat Mass and Abdominal Fat

Vargas (2018) (3) studied trained athletes during resistance training to observe the effects of a ketogenic diet. He concluded that:

  • To achieve a state of ketosis, carbs intake should be reduced to not more than 50 g per day (approx. 10% of the total daily caloric intake).
  • Protein intake should range from 1.2 to 1.5 g per kg, daily.
  • Fats should account for 60 - 80% of the daily caloric intake

Athletes lost fat but not muscle

Compared to a group on a non-keto diet, those following a ketogenic diet "experienced a greater reduction in Fat Mass and Visceral Adipose Tissue" and their Lean Body Mass or LBM (muscle) was maintained: " this research showed no significant changes nor effect size on LBM", which is great for those who diet to lose fat and not muscle, but maybe not optimal for athletes seeking to build up more muscle.

No adverse heart Effects

Kosinski and Jornayvaz, (2017) ( 13 ), found that subjects following a low-carb, high-protein diet were not affected "with higher mortality after 12 years of follow-up" and that the effect of a keto diet on cardiovasular risk factors "are unanimous about general positive effects".

The Brain: Neuroprotective effects of ketones

Alzheimer's, ALD, Parkinson's

The KD has also shown some "promising" effects in several health conditions such as epilepsy, dementia, ALS and traumatic brain injury.

White and Venkatesh (2011) ( 10 ) report that ketones may have a neuroprotective effect: "Studies of Parkinson's disease and Alzheimer's disease confirm the encouraging effects of ketones... Other conditions that may be responsive to ketones include amyotrophic lateral sclerosis and certain brain tumors".

The authors believe that the ketones decrease free radical production. For instance when glutamate, an amino acid that functions as a neurotransmitter, appears in high concentrations in the brain, it causes the death of neural cells, ketones may protect against this effect by oxidizing coenzyme Q and decreasing the formation of free radicals. Ketones can oxidize coenzyme Q, thus decreasing mitochondrial free radical formation. Ketones also increase cerebral blood flow.

Dashti, et al., (2004) (9) report that a KD can act as a mood stabilizer in bipolar illness and also induces gene expression in the brain.

Regarding gene expression, (Noh, 2004) ( 11 ) β-hydroxybutyric acid or BHB acts on the genes that encode certain mitochondrial enzymes in a part of the brain known as hippocampus, the extra energy boost that ketones gives those cells may prevent cellular death and mitigate the effects of age-related degenerative brain diseases.

Clear Mind

Furthermore, a study by Murray (2016) ( 12 ), with rats found that "ketosis improve[d] cognitive performance during a maze test of working memory" and suggested that the brain prefers to use ketone bodies instead of glucose.

Perhaps this is the reason for the un-fogged brain reported by keto dieters on websites that promote this diet.

Take home point

Positive effects on your brain and central nervous system

two overweight women view of rear and thick waist
Obesity, full hips and wide waist

Conclusions

A ketogenic diet or KD is an effective way of losing weight, abdominal fat and improving several indicators such as BMI, total cholesterol, blood sugar and HDL.

It should, as with any diet, be supervised by a nutricionist or a physician. Renal side effects may appear, LDL cholesterol may increase, the transition out of a KD should be gradual, and it has some negative side effects, but also many positive effects.

Cite this article:

. ©2018. Ketogenic Diet: a Review. Patagonia Wellness, 24 Oct. 2018. http://www.patagoniawellness.com/diet-food/keto-diet-review.html

Tags: A review of the ketogenic diet, what is the keto diet, ketogenic diet, keto diet, Obesity, keto diet pros, benefits of the KD

Subject: Review of the Ketogenic diet. An effective diet for weight loss with many health benefits. The science behind a keto diet

 

References and Further Reading

(2) WM. Bortz, Pavle Paul, AC. Haff, and WL. Holmes, (1972). Glycerol turnover and oxidation in man, J Clin Invest. 1972 Jun; 51(6): 1537-1546. doi: 10.1172/JCI106950

(3) Salvador Vargas, (2018). Efficacy of ketogenic diet on body composition during resistance training in trained men: a randomized controlled trial, J Int Soc Sports Nutr. 2018; 15: 31. 2018 Jul 9. doi: 10.1186/s12970-018-0236-9

(4) Wajeed Masood; Kalyan R. Uppaluri, (2018). Ketogenic Diet, 2018, StatPearls Publishing LLC. Bookshelf ID: NBK499830PMID: 29763005

(5) Antonio Paoli, (2014). Ketogenic Diet for Obesity: Friend or Foe?, Int J Environ Res Public Health. 2014 Feb; 11(2): 2092-2107, 2014 Feb 19. doi: 10.3390/ijerph110202092

(6) Gibson AA, et al., (2015). Do ketogenic diets really suppress appetite? A systematic review and meta-analysis, Obes Rev. 2015 Jan;16(1):64-76. doi: 10.1111/obr.12230. Epub 2014 Nov 17

(7) Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA., (2003). 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, J Clin Endocrinol Metab. 2003 Apr;88(4):1617-23

(8) Paoli A, Rubini A, Volek JS, Grimaldi KA., (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets, Eur J Clin Nutr. 2013 Aug;67(8):789-96. doi: 10.1038/ejcn.2013.116. Epub 2013 Jun 26

(9) Hussein M Dashti, et al., (2004). Long-term effects of a ketogenic diet in obese patients, Exp Clin Cardiol. 2004 Fall; 9(3): 200-205

(10) Hayden White and Balasubramanian Venkatesh (2011). Clinical review: Ketones and brain injury, Crit Care. 2011; 15(2): 219. 2011 Apr 6. doi: 10.1186/cc10020

(11) Noh HS, (2004). A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet, rain Res Mol Brain Res. 2004 Oct 22;129(1-2):80-7

(12) Andrew J. Murray, (2016). Novel ketone diet enhances physical and cognitive performance, FASEB J. 2016 Dec; 30(12): 4021-4032, 2016 Aug 15. doi: 10.1096/fj.201600773R

(13) C. Kosinski and F. R. Jornayvaz, (2017). Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies, Nutrients. 2017 May; 9(5): 517. 2017 May 19. doi: 10.3390/nu9050517