Nutritional intervention in bipolar disorder and schizophrenia

The intervention group ("the KD arm") will be asked to follow a well-formulated and nutritionally balanced ketogenic diet (75% fat, 20% protein and 5% carbohydrates) for 12 weeks (+2 weeks introduction "run-in" to the diet and +2 weeks cessation period), taking into account the participants food preferences, allergies and intolerances, food preparation abilities and financial circumstances. The definition of "ketogenic" is based on the ability of the diet to induce the physiological production of ketone bodies ("ketones") by the liver in response to the diminished carbohydrate intake. Such ability is a natural physiological response and as such varies in accordance to the participants' sex, underlying metabolic state and long-standing dietary habits. During the 2-week run-in period, the participant will for the first five days be required to only change their breakfast meal. On day six, the participants will be required to change the lunch meal as well (at this point, they are on their specified diet both morning and lunch). On day eleven, the dinner meal will be required to be changed into the specified diet, resulting in a complete change of diet. Similarly, during the cessation period, the participant will start by changing one meal back to "normal" for 5 days, then 2 meals and after 11 days, the participant will be back to their previous dietary habits. If the participant decides to continue the diet after the study has ended, they will not be required to stop it after week 14. Support from a dietitian and a team member will be offered for up to 3 months. The KD arm will therefore receive an individualised nutritional assessment and advice by a qualified dietician experienced in therapeutic KD that will maximise the efficacy and safety of the KD in each case. The assessment will occur as soon as possible following the randomisation into the treatment group and will last approximately 60 minutes. Following the assessment, the participants in the KD arm will receive informational material in the form of a KD Handbook (designed specifically for this study) containing the principles of the diet; necessary information to understand different macro and micronutrients relevant to the diet; education around the most common side effects of being on a KD and how to manage them; a collection of illustrated, easy to follow recipes to help the participants' daily compliance with the diet; Daily readings of peripheral blood ketone and blood glucose levels will be monitored in order to ensure safety of, and compliance with, the diet. The participants will be asked to text a picture of their digital device showing ketones and blood sugar levels; as an optional alternative, they may send a text with the results to the team or receive a phone call by a team member instead. With appropriate consent in place, family members and/or carers will be encouraged to support the participant with their food sourcing, meal preparation, and blood test monitoring. If necessary, in view of poor adherence to the diet by a participant or at the participant's own request, additional education by a team member under strict supervision of the dietitian and senior psychiatrists in the team, will be delivered to the participants or to their families or carers to ensure adherence to the KD.