# Ketogenic Diet Plus Resistance Training Applied to Physio-Pathological Conditions: A Brief Review
## 2 Ketogenic Diet Applied to Physio-Pathological Conditions Not Cancer Related  
It is noteworthy to mention that older phenotypes might experience a slower glycogen depletion and ketogenesis rate [8], possibly due to an impairment of metabolic switching [9]. Even if using urine strips to assess ketosis is a common practice, practitioners and consumers should be cautious of potential false negatives [10]. For instance, BHB, one of the major ketoacids, does not react with nitroprusside in dipsticks. Hence, using self-blood monitoring for ketoacids is recommended. About one hundred years since its first application for the management of epilepsy [11], the KD has undergone numerous developments [12]. It is frequently employed as a non-pharmacological therapy in various physio-pathological conditions, such as, first of all, neurological disorders [13;14], polycystic ovary syndrome (PCOS) [15], obesity and lipedema [13;16;17], and, importantly, as a supportive measure for metabolic disorders [13;18]. It should be noted that the KD and other low-carbohydrate configurations are frequently used during a hypoenergetic diet to promote weight loss and improve body composition [19]. Several studies as part of the Curves Women's Health & Fitness Initiative at the Exercise & Sport Nutrition Laboratory  
Figure 1: Scheme of cell during ketogenic diet vs normal diet: (**A**) Increase in ketone body level as a result of fatty acid oxidation, thus enhancing level of acetyl-CoA in mitochondria to compensate for the ATP needed. (**B**) Glucose is fully oxidized through glycolysis followed by the mitochondrial Krebs cycle coupled to oxidative phosphorylation. Created with BioRender. (Texas A&M University) have demonstrated that a carbohydrate-restricted diet promoted more favorable changes in weight loss, fat loss, and markers of health in obese women who initiated a circuit-style resistance training program compared with a diet higher in carbohydrate [20; 21; 22]. In fact, it seems that greater improvements in body composition are achieved when carbohydrates are replaced in the diet with protein, in general [23]. Similarly, the KD involves a high fat intake, accounting for up to 80% of total calories. Importantly, the protein/fat ratio varies based on the intended goal; for example, a 4:1 ratio for fat/protein intake has been discussed for pediatric epilepsy [24], and our research group has applied the 2.5:1 ratio to manage lipedema [16]. Its clinical use as well as short- and long-term non-desired effects [16; 25; 26; 27; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43] are listed in Table 1.  
Hence, despite its popularity, the KD should not be selected only under hypoenergetic conditions and the isocaloric ketogenic diet (ICKD) might be preferable if the aim is to support seizures, immune function, PCOS, and muscle status [44]. Although there are still relatively few studies on this topic, it seems that the ICKD could serve as a viable alternative to traditional diets, particularly in pathological conditions. For instance, [PERSON] et al. [45] demonstrated that just three days of the ICKD led to improvements in inflammation-related parameters, particularly in regulating the inflammasome. This is of particular importance, if we consider the anti-inflammatory action through the modulation of nuclear factor-\(\kappa\)B (NF\(\kappa\)B) and the nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as Nrf2) [45]. Also, in a systematic review, [PERSON] et al. concluded that the ICKD could be beneficial in supporting the treatment of various types of tumors [46]. This is probably because cancer cells, known to use glucose preferentially as a substrate for growth, with a mechanism known as the Warburg effect, are delayed in their progression because of this metabolic alteration. In any case, here we want to discuss more regarding the KD applied to decreasing cancer levels.