2. Ketone Bodies Are a Great Alternative to Sugar to Fuel the Brain
3. KD Fights Degeneration and Inflammation
4. Brain Mitochondria Love Ketone Bodies
5. KD Improves Brain Health and Cognition, and Corrects Neurotransmitter Imbalances
6. KD Promotes Weight Loss, Improves Body Composition
7. KD Improves Signs and Symptoms of MS
8. KD- Misconceptions and Warnings
9. My Thoughts
1.What is Keto diet and a brief history
-Has been researched and used since the 1920s as a therapy for epilepsy (this diet can remove the need for antiepileptic drugs in some cases)
-Researchers first noticed the benefits of fasting, then found that KD mimics the effects of fasting
-Since the 1960s till date, KD had been mostly known for weight loss (extensive research on its metabolic effects from Dr. Cahill and colleagues and Dr. Atkins) [1]
-It appears that KD is even referenced in the Bible in the story of a cured epileptic (New Testament, Matthew 17:14–21) [1]
-We now have many versions of KD, ketone bodies in supplement form, and a fasting mimicking diet (Dr V Longo).
-KD has been studied for various conditions, showing benefits for weight loss, heart diseases, type 2 diabetes, epilepsy (strongest evidence) as well as MS, Parkinson’s , Alzheimer’s, amyotrophic lateral sclerosis, brain trauma), PCOS, acne and cancer.
2. Keto bodies are a great alternative to sugar to fuel the brain
Traditional diet (high carbs- i.e. carbs 50% proteins 20% fats 30%).
You eat a high carb meal ——–>Your pancreas secretes insulin——>Insulin shuttles glucose in the cells —->Energy.
You eat a very low carb meal——-> Fat will break down into ketone bodies in your liver —-> keto bodies in the cells—–>Energy.
When carbohydrates are restricted from diet, the brain will use the fat. Fat can’t be used directly as a source of energy, and thus fat is converted into ketone bodies during a process called ketogenesis (not to be confused with diabetic ketoacidosis, which is a different process). Ketogenesis takes place in the mitochondria of the liver, and the main ketones are beta-hydroxybutyrate, acetoacetate, and acetone. These ketone bodies replace the glucose as a main source of fuel for the brain as they easily cross the blood brain barrier. Ketone bodies are able to produce more energy compared with glucose [1], [2], [3].
Technical: The brain’s usage of ketone bodies raises proportionally with their increase in serum concentration ( up to a concentration of 12 mmol/L). According to a meta-analysis (animal models), the brain metabolic rate of glucose is reduced by 9% with every 1 mmol/L increase in total plasma of the ketone bodies. Ketone bodies have the ability to bypass the glycolytic pathway and directly enter the Tricarboxylic Acid cycle within mitochondria, thus playing a role in anaplerosis.
3.Keto diet fights degeneration and inflammation.
Helping your body run on ketone bodies is beneficial not only for treating seizures (as it was originally designed for), but also for other conditions affecting the brain. This happens because KD protects the brain cells against damage and degeneration by supporting healthy mitochondria. Ketone metabolism also runs more efficiently than glucose metabolism. Like other low carb diets, keto diet also helps reduce inflammation by reducing inflammatory markers that are linked with degeneration [4].
Technical : KD inhibits neuroinflammation by suppressing a COX-2-dependent pathway via activation of PPARγ by the KD or acetoacetate [5]. PPARγregulate both inflammatory and multiple other pathways that are implicated in neurodegeneration.
4. Brain mitochondria love ketone bodies.
MS is strongly associated with mitochondrial dysfunction, and this dysfunction leads to neurodegeneration.
KD was found to improve mitochondrial function by reducing oxidative stress and boosting the antioxidant levels, thus raising the ATP molecules availability. KD also appears to directly preserve ATP levels in case of mitochondrial dysfunction and plays a key role in the formation of new mitochondria (a process called mitochondrial biogenesis).
Technical: The decrease of oxidative stress derives from its effect on uncoupling proteins (UCPs) . Keto diet promotes UCP2, UCP4, and UCP5 with corresponding decrease in reactive oxygen species. Ketones bodies can activate Sirt1 in neurons and reduce activity of mTORC1(animal studies) [5]. Keto diet increases the antioxidant levels (particularly catalase and glutathione) by inhibiting the action on histone deacetylases and by activating the Nrf2 pathway [6].
5. Keto diet improves brain health and cognition, and corrects neurotransmitter imbalances.
There is an increasing amount of research showing that KD increases the levels of adenosine (a chemical with strong anti-inflammatory and immunomodulatory qualities that also promotes brain cell repair). This relationship between adenosine and KD basically helps reset the brain metabolism and improves the brain cells’ activities [7].
A very low carb (keto type) diet has been found to improve cognition and verbal memory performance in elderly adults, after only 8 weeks.
Keto diet also increases GABA (a deficiency of this neurotransmitter is linked with increased disability in progressive MS), decreases glutamate (excess glutamate levels are strongly correlated with MS and loss of brain function)[8], [9], [10], [11].
Technical : Excessive activation of the glutamatergic pathway plays a key role in the development of MS. Besides the well known direct toxic effect in the neurons, glutamate induced cell damage had been found in oligodendrocytes, astrocytes, endothelial cells, and also in the immune cells. These multiple cell damage could explain different pathological aspects found in MS such as axonal damage, OL cell death, demyelination, autoimmunity, and even the BBB dysfunction [12].
Keto decreases glutamate toxicity. Acetoacetate and β-hydroxybutyrate inhibit vesicular glutamate transporters. The filling of glutamatergic synaptic vesicles by vesicular glutamate transporters requires the presence of chloride ions outside the vesicle. Both acetoacetate and β-hydroxybutyrate block glutamate transport into synaptic vesicles and shift the chloride dependence of the transporters to higher chloride concentrations. Acetoacetate is more potent than β-hydroxybutyrate[13].
6. Keto diet promotes weight loss and improves body composition.
There is no doubt that ketogenic diets are effective for losing weight. KD helps improve body lean mass while decreasing body fat [14] and KD improves testosterone levels (when compared with western diet)[15], [16].
Technical : KD- for weight loss 4 mechanism of actions proposed: 1.Decrease in appetite due to higher satiety derived from protein intake, effects on the hormones that control appetite and possibly a direct appetite suppressant effect; 2. Decreased lipogenesis and increased lipolysis; 3. increased metabolic efficiency in consuming fats; 4. Increased metabolic costs of gluconeogenesis and the thermic effect of proteins [16].
There is some evidence that it has anti-aging qualities and mid-life mortality, and help reverse autoimmune response. Genetic factors also influence how you respond to a ketogenic diet. [R], [R], [R].
7. KD improves signs and symptoms of MS.
KD decreases neuropathic pain (numbness, tingling) and inflammation, as it has anti-inflammatory and analgesic qualities. Compared to glucose metabolism, ketone metabolism produces fewer reactive oxygen species – which are known to contribute to inflammation [17].
KD was found to reverse brain lesions and decrease brain inflammation and oxidative stress [18]. KD improves motor disability, cognitive impairment, anxiety and depression (in animal model of MS) [19].
8. KD- Misconceptions and warnings
1. Ketosis from KD or fasting is different from diabetic ketoacidosis. Ketosis is a normal physiological mechanism, also known as “physiological ketosis” described by biochemist Hans Krebs. The blood levels of KB reach a maximum of 7/8 mmol/l and won’t go higher because the brain uses KB efficiently instead of using glucose, and the pH is normal. Diabetic ketoacidosis is an abnormal, pathological ketosis where KB blood levels can exceed 20 mmol/l and a lower blood pH [20].
2. Get into ketosis gradually, to avoid thyroid problems. When you switch from high or normal sugar diet to a low or very low carb diet you may experience symptoms of low thyroid hormones (i.e. feeling tired, cold feet and hands, digestive problems). Routine thyroid tests may look normal, but advanced tests such as rT3 (reverse T3 hormone) may be high. These change in rT3 is reversible but it can be avoided by cutting down the amount of carbs over a few days. I need to do more research, as I suspect low T3 and rT3 may not be as bad as we have previously thought, in the context of ketosis [21], [22].
Other side effects include: flu-like symptoms (headache, fatigue, lack of motivation , brainfog ), leg cramps, constipation, heart palpitations, decreased physical performance), are usually caused by dehydration and loss of salt, potassium and magnesium. They are temporary symptoms, as the body needs to adjust to burn fat versus glucose. The best way to avoid these side effects is to drink plenty of water and replace minerals (caution with salt supplementation, because low salt intake is actually beneficial for MS [23].
Overall, KD helps improve cholesterol levels long term, however, a very small percentage (1-2% ) of people may experience an increase in total cholesterol and LDL levels.
3. KD should not be used during pregnancy or or lactation [24], [25].
KD has many health benefits and can help manage MS. It may be suitable for many, but not for everyone. Consider a personalized nutrition and seek professional advice when starting a diet like KD. KD should not be used for a long time, but rather cyclically and alternately with non-keto/other low carb diets.
Ketone bodies are tested in a similar way with glucose, with a home test kit. Combining KD with a low lectin diet could further improve its efficacy, as KD targets mostly neurodegeneration (and to a lesser extent inflammation), while low lectin diet would work on the autoimmune component and neurodegeneration. No studies in humans yet, but I think KD is likely to improve longevity considering its impact on key proteins and pathways linked with lifespan (SIRT proteins, mTOR).
Protein intake should be moderate, not high. Excessive proteins convert in sugar, which then turns into fat. Too much protein in the diet can get you out of ketosis, plus increase the risk of kidney stones, osteoporosis, and other issues. KD should be used along with some supplements (ie magnesium, potassium) to avoid muscle cramps and other symptoms of nutrient deficiencies [27], as well as digestive enzymes with ox bile (to help break down the fats), and of course, more water as dehydration can be a problem. Extra fibers and prebiotics are needed as this diet may not provide enough.
