**1. Introduction**

Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system (CNS) that causes a progressive deterioration of the myelin sheath associated with axonal injuries at a neuronal level, leading to functional disability. This neuronal damage is mainly based on high oxidative stress and inflammation in the central nervous system, affecting the permeability of the blood–brain barrier (BBB) and allowing autoreactive T cells, B cells, macrophages and microglia to access and especially damage the white matter in the brain and spinal cord [1–3].

Due to the inflammatory nature of MS, several inflammatory markers have been related to the disease, especially interleukin 6 (IL-6) whose levels are significantly high in MS patients [4]. Thus, it has been demonstrated that T cells in MS patients have more IL-6 receptors in peripheral blood than healthy individuals [5]. Due to the fact that it is an inflammatory marker, the amounts increase when the person is overweight or obese, which is determined by means of anthropometric parameters, such as the body mass index (BMI) [6] that is correlated with the individual's adiposity [7]. Clinically speaking, there is a relation to characteristic aspects of the disease, such as relapses and functional disability [4], and with its pathogenesis [8].

Nonetheless, patients with a higher concentration of IL-6 in serum show higher levels of anxiety [9]. Thus, the most anxious individuals have higher levels of IL-6, regardless of their age or gender [10]. Anxiety has been observed to influence the level of inflammation, increasing the risk of developing inflammatory diseases [11]. The influence of anxiety is due to a transcriptional pattern observed in animal models, in which monocytes are recruited that specifically depend on the increase of IL-6 in serum [12], once anxiety in stressful situations is caused. As a result of this link between the high levels of IL-6 and the perception of anxiety, we can see that anxiety disorders are found amongst the most common psychiatric disorders associated with MS [13]. In addition, anxiety symptoms have an effect on the course of the disease, increasing the levels of fatigue [14] and especially functional disability [15].

In this sense, ketone bodies obtained through hepatic beta-oxidation have shown improvements in inflammatory markers, including lipid markers, glycated haemoglobin (HbA1c) or high-sensitivity C-reactive proteins that are related to an increase in the total antioxidant state in blood [16]. Particularly in MS, the ketone body β-hydroxybutyrate (BHB) activates HCA2 receptors expressed by neuroinflammatory cells, reducing neuroinflammation [17] and achieving a neuroprotective effect [18]. In addition, ketone bodies have decreased the perception of anxiety in animal models with Alzheimer's disease, where an anxiolytic effect of the ketogenic diet has been observed [19], and in humans of advanced age [20]. Regarding the nutrients capable of providing higher levels of ketone bodies in blood, those with high levels of medium-chain triglycerides (MCTs) stand out, with coconut oil possibly being the food with the highest amount of MCTs, due to the high percentages of medium-chain fatty acids (MCFAs), such as lauric acid, palmitic acid, stearic acid, myristic acid and oleic acid [21]. These acids are absorbed intact and do not suffer degradation and reesterification processes [22].

On the other hand, epigallocatechin gallate (EGCG) is a polyphenolic catechin with a high antioxidant and anti-inflammatory activity [23,24]. EGCG's protective effect allows it to be especially efficient in autoimmune diseases, such as MS, as it promotes the repression of autoreactive T cell proliferation, a reduced production of proinflammatory cytokines, a decrease in Th1 and Th17, as well as an increase in the regulatory T cell populations in lymphoid tissues and the CNS [25]. It also takes the spotlight due to its capacity to penetrate the blood–brain barrier [26] and to accumulate inside the mitochondria of the neurons, decreasing apoptosis due to the high oxidative stress of the disease [27].

Finally, EGCG is also related to an emotional improvement, especially in terms of anxiety, as the activity of GABA receptors is modulated [28]. This would explain the decrease in anxiety after administration in CNS diseases, such as schizophrenia [29]. Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6 and anxiety related to functional disability in MS patients.

### **2. Materials and Methods**

A prospective, mixed and experimental pilot study was conducted by means of a clinical trial.
