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Do or Die-t | The Ketogenic Diet

Of the many diets out there, the one that tops the list as the most maligned or frowned upon seems to be The Ketogenic Diet or Keto. So I thought, it would be best to start explaining what the Keto diet is in layman terms. The purpose of this series "Do or Die-t" is to educate my readers as to the pros and cons the top 5 weight loss diets. Let's start with the Keto Diet (KD).

What is the Keto diet?

  • A diet that has 70% of calories coming from fats, 20% coming from protein and 5% coming from carbs. It comes under the umbrella of LCHF (low carb high fat), so while Keto is LCHF, not all LCHFs are keto.

  • The word "keto" comes from Ketones. That is, your body is in a state of Ketosis. Ketones are the by-product of fat metabolism produced by the liver and is used as an energy source when glucose is not readily available. Ketosis is the metabolic state in which your body accumulates ketones faster than they’re being burned.

How Ketones are formed?

  • When we fast, or when we completely avoid carbohydrates for a long time or deplete our glycogen stores in the muscle and liver, the body utilizes its fat stores to be used for energy. Body fat is broken down into fatty acids and glycerol molecules.

  • Most cells throughout the body can use fatty acids and glycerol as fuel but with the brain that is not the case because the breakdown of fatty acids and glycerol into energy is too slow for our energy-sucking brains.

  • So to provide an alternative fuel to our hungry brain (in absence of glucose), fatty acids and glycerol molecule enter the liver and gets converted into Ketones and glucose. Two processes happen here: Gluconeogenesis, which converts glycerol into glucose, while the fatty acids are converted into ketone bodies through a process called Ketogenesis. (P.S: The brain will never entirely give up glucose and run on ketones completely. Even on an extended fast, the brain still runs on 40% glucose, 60% ketones).

What are the three types of ketone bodies?

So, fatty acids in the liver first convert into a molecule called acetyl-CoA. The three types of Ketone bodies synthesized from this are

  • Acetoacetate: This is the first molecule that is created from acetyl-CoA. It is then converted by the liver into Beta-hydroxybutyrate.

  • Beta-hydroxybutyrate [BHB]: This is the most abundant out of the three Ketone bodies.

  • Acetone: is generated through the decarboxylation of acetoacetate and is mostly excreted as waste.

How do we know we are in a state of Ketosis?

The only way to know if by measuring your ketones. This can be done by:

  • Urine test

  • Breath test

  • Serum/ blood test

Many people wrongly assume that cutting out grains alone means we are in a Keto Diet, or having high protein is equal to being in a state of ketosis. That is simply not the case.

How does stored body fat leave the body?

As we know the law of thermodynamics - energy can neither be created nor destroyed, but can be transformed from one form to another, right? So what happens to the 5kgs we lost? Where has it all gone? We've pee-ed it out or breathed it out. Yep! Through a long series of chemical processes, fat leaves our body through urine or our breath. That is why people who start off on a Keto diet tend to have the "keto breath". This is how we get to measure our ketone levels too.

So yes, it is natural to see ketones present in urine in the first months of active weight loss on a LCHF diet, but over time, your body gets efficient at producing ketones and once weight loss stabilizes or you introduce carbohydrates, ketones in urine become untraceable.

 

15 Benefits of the Ketogenic Diet


So I've spent some time compiling the list of benefits and studies on the KD and I'm leaving links to the studies that support each point for my nerdy folks on here.


1. Overall health benefits with Keto

The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.

2. The Keto advantage for weight loss

The subjects were put on one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non– restricted-calorie diet. Among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively.

3. Keto has a positive effect on the mitochondria

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867088/ These data show that a calorie-restricted KD enhances brain metabolism. Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging.

4. Ketones and reduction in oxidative stress

https://pubmed.ncbi.nlm.nih.gov/7768357/ Ketones don’t just provide energy but they provide a more efficient fuel source when compared with glucose. Glucose metabolism yields 36 ATP (adenosine triphosphate) molecules whereas fat metabolism yields 48 molecules of ATP (which is the unit for cellular energy). Glucose metabolism causes more oxidative stress and the creation of free radicals, which in turn will speed up aging whereas beta-hydroxybutyrate (a ketone body) is associated with a reduction in the generation of reactive oxygen species by the mitochondria.

5. Keto increases BDNF that in turn increase neuroplasticity

https://www.ncbi.nlm.nih.gov/pubmed/22787591 A ketogenic diet is said to increase BDNF levels. BDNF stands for Brain Derived Neurotrophic Growth Factor and is a key neurochemical responsible for the growth and maintenance of neural connections.

6. Keto Diet balances GABA and glutamate, improving anxiety

Studies have shown that a Ketogenic diet increases glutamic acid decarboxylase (GAD) enzyme, which is needed for glutamate to make the conversion to GABA, and neurons can use ketones produced from ketosis as a precursor to GABA. Glutamate and gamma-aminobutyric acid (GABA) are the most common types of neurotransmitters. Following a Keto diet would be ideal for maintaining balance between gamma- aminobutyric acid and glutamate. People with anxiety disorders report improved focus, mental clarity and less anxiety on the Keto Diet.

7. Keto lowers the risk of Alzheimer's Disease

Alzheimer's disease is considered as Diabetes Type 3, or Insulin Resistance of the neurons in the brain. Studies have demonstrated efficacy in animal models of neurodegenerative disorders and in human clinical trials, including Alzheimer’s Disease trials. Much of the benefit of Ketone bodies can be attributed to their ability to increase mitochondrial efficiency and supplement the brain's normal reliance on glucose. Research into the therapeutic potential of Ketone bodies and ketosis is promising.

9. Keto diet for diabetes type 2, glucose management and insulin resistance

It was a 16-week study that proved that the KD was effective in improving glycemia and reducing medications in patients with type 2 diabetes. Another study documents the obese patients who were diabetic and put on a low-carbohydrate ketogenic diet. After 44 months observation time, without close follow-up it concluded that for obese patients with type 2 diabetes to follow a 20% carbohydrate diet with some caloric restriction the KD had lasting effects on body weight and glycemic control. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424054/

10. Keto inhibits cancer cell growth

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235292/ This article published in The International Journal of Cancer states that ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Please note that there are no conclusive clinical trials yet for humans. Studies have indicated that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy.

11. KD lowers triglycerides

This study concludes that weight loss induced by carbohydrate restriction favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease.

This study shows that plasma LDL cholesterol and triglycerides were significantly reduced by 8.9 and 38.6%, respectively for men on a 12-wk carbohydrate restricted diet.

12. KD relieves symptoms of Parkinson’s

One recently published clinical study tested the effects of the ketogenic diet on symptoms of Parkinson’s disease. In this uncontrolled study, Parkinson’s disease patients experienced a mean of 43% reduction in Unified Parkinson’s Disease Rating Scale scores after a 28- day exposure to the ketogenic diet. All participating patients reported moderate to very good improvement in symptoms.

13. KD can effectively be used to treat PCOS

The results of this study suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS.

14. Ketogenic diet as a metabolic treatment for mental illness

Psychiatric conditions, such as schizophrenia, depression, bipolar disorder and binge eating disorder, are neurometabolic diseases that share several common mechanistic bio-pathologies. These include glucose hypometabolism, neurotransmitter imbalances, oxidative stress and inflammation. There is strong evidence that ketogenic diets can address these four fundamental diseases, and now complementary clinical evidence that ketogenic diets can improve the patients' symptoms.

15. KD is effective in suppressing appetite making you eat less and feel full for long

This study suggests there is benefit in a ketogenic diet as it prevents an increase in appetite, despite weight loss, with individuals feeling slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite.

 

5 Pitfalls of a Ketogenic Diet


While there are many anecdotal accounts of the dangers of a Ketogenic Diet (haven't we had at least one person scare us about our kidneys with KD?) very few studies have been done on the long term effects of Keto. However, what I've managed to read upon and research are the pitfalls on the extreme versions of Keto. As we know, Keto is a very low-carb, high fat diet with 70% of calories coming from fats and 5-10% coming from carbs. I have come across many people who don't do the Ketogenic diet properly but instead their version of Keto, like high carbs and high fat, or an excess emphasis on dairy, exogenous ketones etc. This is where we veer into dangerous territory.

1. Weight gain - Most people turn to KD to lose weight as it is one of the most effective diets for weight loss. But over and above the work and action of hormones, calories do matter. Fats have calories. Further, dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. Sustained insulin resistance is a contributing factor to weight gain.

2. Increase in Low Density Lipoprotein Cholesterol (LDL-C) - This seems to be a common occurrence among Keto dieters, but it isn't as simple as "high fat increases cholesterol". It is because of decreased insulin production that inhibits 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activation and stimulates HMG-CoA lyase involved in ketone production. What this does is that it decreases liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels. Thus, following a low carbohydrate diet inadvertently leads to increased production of LDL-C (not a high fat diet!)

3. Very low insulin levels - We know that one of the main functions of insulin is to regulate the body's energy sources and to supply the body's cell with glucose for ready fuel. Besides this, insulin also controls electrolyte balance within the cells. When insulin levels fall very low (which is sometimes the case on a KD), blood glucose levels rise as insulin produced by the pancreas isn't enough to move this circulating blood glucose into the cells. This leads to hyperglycemia (or high blood sugar) and if left untreated can lead to Diabetes type 1 (though a autoimmune condition, but is essentially a situation of high blood sugar and very low insulin). Other conditions that can arise is Pancreatitis. A person with hyperglycemia will show symptoms of fatigue, brain fog, paleness, nausea, shakiness / giddiness and hunger. The normal range of fasting insulin varies somewhat between labs, but around 2 to 20 mIU/mL is considered normal by most, with 3-9 being optimal. Anything less than 2 is dangerous.

Insulin deficit leads to the significant increase in glucagon plasma concentration. Glucagon is an antagonist of insulin. Glucose synthesis from glycogen by gluconeogenesis in the liver significantly increases when insulin is unable to inhibit glucagon effects. At the same time, utilization of glucose by liver, muscles and adipose tissue decreases. Ultimately, these processes result in hyperglycemia. Hyperglycemia is further progressed due to activity of other hormones having antagonistic action to insulin. They include cortisol, epinephrine, somatotropin.

4. Electrolyte imbalance - In continuation to the previous point, Insulin shifts potassium into cells by stimulating the activity of Na+-H+ antiporter on cell membrane, promoting the entry of sodium into cells. Insulin is a potent stimulus for hypokalaemia (low potassium), sparing body potassium from urinary excretion by transporting it into cells. Potassium also appears to play a key role in the antinatriuretic effect of insulin.

Insulin stimulates all the transporters involved in Na absorption from proximal tubules. The effect of hyperglycemia is well known for its lowering of serum sodium levels.

5. Non-Diabetic (or Metabolic) and Diabetic Ketoacidosis - These terms are often thrown around and confused with the term "Nutritional Ketosis". Ketoacidosis is rare. Insulin deficit accelerates protein catabolism. Amino acids formed in this process can also contribute to gluconeogenesis in the liver resulting in deterioration of hyperglycemia severity. The massive breakdown of lipids in adipose tissue leads to the strong increase in free fatty acid plasma levels. This in turn leads to accumulation of ketone bodies which are products of free fatty acid degradation. In other words, Diabetic Ketoacidosis develops when your body doesn't have enough insulin to allow blood sugar into your cells for use as energy. Instead, your liver breaks down fat for fuel, a process that produces acids called ketones. When too many ketones are produced too fast, they can build up to dangerous levels in your body.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199956/ --> This study explains very simply what happens in the state of Ketosis and what happens in Ketoacidosis.

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