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As suggested in a recent meta-analysis, it is challenging to define a ‘threshold’ of circulating ketone for appetite suppression(131). In addition, a large number of ad libitum eating studies showed that KD resulted in lower energy intake(86,89). A meta-analysis study showed a lower hunger and desire for energy intake in individuals adhering to KD(131). Furthermore, it has been proposed that limited food choices may be another cause of decreasing energy intake in KD’s followers(129,130). The Liver-derived fibroblast growth factor 21 is an endocrine regulator of the ketotic state and maybe another possible mechanism for appetite suppression following KD(126). Moreover, other studies have shown a decrease in leptin and increased ghrelin concentrations, which are two hormones that regulate satiety; however, these effects were mitigated when BM-reduced participants were ketotic(119,124). It is insufficient to compensate for the decrease in NEFA release through insulin secretion in response to carbohydrates, usually consumed, and fats(104). KD are based on the premise that reducing carbohydrate intake results in increased fat oxidation. The participants with the low-fat-responsive genotype were observed to lose more BM when assigned to an LFD than those assigned to an LCD, and vice versa for those with the low-carbohydrate-responsive genotype(99,100). Moreover, some studies have reported that genotype variation could predispose individuals to differentially respond to BM loss influenced by diet type(98,99). However, some studies did not reveal differential effects following the low fat v. LCD on BM loss by baseline insulin status(96,97). A combined preclinical therapy of cannabinoids and temozolomide against glioma. An open-label study of cannabis-based extracts for bladder dysfuntion in advanced multiple sclerosis. 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