Neuroprotective protocol OPIK: oral pyruvate plus intermittent Ketosis
Creators: name: Zilberter, Tanya
name: YURI ZILBERTER
Publisher: name: F1000 Research Limited
Year: 2018

description: JUSTIFICATION OF OPIK<br>The proposed protocol is a synthesis of two known effective neuroprotective regimes: ketogenic diet (KD) and intermittent fasting (PG). This combination avoids the difficulty of adhering to a ketogenic diet that reduces the likelihood of compliance, and its unwanted side effects.<br><br>ORAL PYRUVATE<br>Pyruvate is a powerful neuroprotective agent (Zilberter, Gubkina, Ivanov, 2015, Koivisto et al., 2016).<br>• Increases energy in the brain in the form of glycogen:<br>• Increases the resistance of neurons to ischemia;<br>• Reduces neurotoxicity in hyperactivity;<br>Has a strong anti-inflammatory effect.<br><br>However, there is an important protective function on which pyruvate is incapable, but to which a ketogenic diet is capable: epigenetic activation of the endogenous antioxidant system.<br><br>KETOGENIC DIET<br>The positive effects of ketogenic diet (KD)<br>1. KD prevents the hypometabolism of the brain - the pathophysiological state characteristic of neurodegenerative diseases, including epilepsy. [35-43] *.<br>2. Neuronal hyperactivity in epileptogenesis is weakened with KD [40, 48-54].<br>3. KD improves glucose control, whereas HDL causes glucose intolerance [64-68].<br>4. KD improves cognitive performance in patients with epilepsy (vocabulary, reaction time and attention) [82].<br><br>PROBLEMS WITH OBSERVING KD<br>The main problems of KD are: a) the difficulties of its compliance, leading to stress and feelings of deprivation, and b) the actual metabolic deprivation that leads to a deficiency of water-soluble vitamins and, especially when drinking is restricted, problems with water-salt metabolism. The modern attempt at a compromise between the useful and undesirable effects of KD led to the wide application of the protocol "Modified Atkins", the ketogenic ratio of which was three times lower than that of KD, and the efficacy in epilepsy was 37% lower [13, 22, 23] **.<br><br>POSITIVE EFFECTS OF INTERMITTENT FASTING (IF):<br>PG is achieved by chronic restriction of the "food intake window" to 4-8 hours during the day. PG improves glucose control and insulin sensitivity, and also includes a direct antiepileptic calorie restriction effect, as it leads to a voluntary reduction in energy intake with food up to 400 Kcal per day (Zilberter &amp; Zilberter, 2014). PG showed long-term neuroprotective effects in the prevention of neurodegenerative diseases. In the experiments, improvements in synaptic plasticity and cognitive function were observed.<br><br>INTERMITTENT KETOSIS (IK).<br>The first and for centuries the only treatment for epilepsy was complete starvation. KD appeared as a metabolic imitation of fasting, which gave grounds to assume that the IK can be considered as a metabolic analogue of IK (Zilberter, 2011). The PC as a metoprotective regimen was proposed in 1991 by Heller &amp; Heller, who rationalized the significant practical success of their followers with the above effect on insulin sensitivity (Heller &amp; Heller, 1994).<br><br>The diet continues to be successful. Its foundations are close to our understanding of a regime that combines efficacy, nutritional value and the absence of adverse effects. We analyzed the responses of 423 people who adhered to this regime (Figure 1). Participants noted that it was easy for them to follow a diet, that they had decreased appetite, decreased weight, and that there was no feeling of stress and / or deprivation.<br><br>IK APPLICATION<br>Our IK version was included as one of the options in the Banta Diet program (2010), tested in 2002-2004 by 1,300 participants with an efficiency of 92%<br><br>The state of ketosis, which begINS during the night sleep, is prolonged by the morning hot drink (prescription is attached) with a very high ketogenic ratio of 1: 8.45 (which we proposed for simplicity to be called "ketogenicity"), which is more than twice the ketogenicity of a strict classical KD. The amount of such a drink is not limited. According to the opinions of our participants, the taste of the drink is more than satisfactory.<br><br>The last food intake is recommended no later than 6 pm. We instruct him to begin with a large portion of a salad, based on green leafy vegetables as a source of vitamins, fibers and phytonutrients. After salad, any food is allowed, but the total meal time should be limited to one hour. If necessary, another hot drink according to the prescription, based on herbal teas, is allowed.<br><br>In case of insufficient individual effectiveness of the plan, we offer special recipes for the main meal, having a ketogenicity above 2, that is, above the threshold of ketogenicity.