Nutrition for Precision Health, Powered by the All of Us

The goal of this investigational study is to develop algorithms that predict human response to foods. The main question it aims to answer are:How does varying foods and eating patterns impact one's biological and physiological responses?In what ways can novel dietary assessment measures be used to improve dietary assessments and to prescribe assessments to people in future research with increased precision?Can artificial intelligence and machine learning techniques be combined to prescribe foods and eating patterns to individuals for optimization of their health?There are 3 Modules participants may take part in:Module 1- A participant's dietary intake and accompanying nutritional status, biological and other measures will be observed over 10 days, as well as physiological responses to a liquid mixed meal tolerance test will be measured.Module 2- Participants will undergo three controlled dietary interventions provided for 14-days each and separated by washout periods of at least 14 days. Physiological responses following a diet-specific meal test will be measured.Module 3- Participants will undergo the same three dietary interventions during the same 14 day periods as Module 2 while being studied in-residence. Physiological responses following a liquid mixed meal tolerance test and a diet-specific meal test will be measured.

Inclusion Criteria:Overall Inclusion -- Participants 18 years of age or older who have completed the primary All of Us consent process, Electronic Health Record consent process, and genetic Return of Results consent process (any answer), have provided at least one All of Us biospecimen suitable for DNA sequencing, and have completed All of Us Participant Provided Information (PPI) Modules 1-3 (Basics, Overall Health, and Lifestyle); Speak English or Spanish; Able and willing to comply with study requirements and consent to participate.Module 1 -- Must be willing and able to comply with Module 1 protocol; Must provide informed consent for Module 1.Module 2 -- Must have completed Module 1; Must provide informed consent for Module 2; Must agree to comply with protocol over a period of approximately 10 to 12 weeks and up to six months. This includes consuming only the foods provided during periods of controlled feeding. Module 2 has three controlled feeding periods each lasting two weeks with at least two weeks between feeding periods, and up to 6 months allowed for completion of the Module.Module 3 -- Must have completed Module 1; Must provide informed consent for Module 3; Must agree to comply with protocol over a period of approximately 10 to 12 weeks and up to 6 months. This includes being domiciled three times, for two weeks each, and consuming only the foods provided during the domiciled periods. There is at least two weeks between domiciled periods, and up to 6 months allowed for completion of the Module.Exclusion Criteria:Module 1Any change to the participant's status from the time of All of Us enrollment that would render them ineligible for All of Us (e.g., being incarcerated, no longer living in the United States, or withdrawn from that study).Inability to provide informed consent and engage in informed consent proceduresParticipants who suffer from allergic reactions to, or are unwilling to consume, any components of the liquid mixed meal (e.g., milk products, berries)Barriers to safe insertion of peripheral IV canula:Contraindications to peripheral IV canula insertion such as local skin infection, inflammation, trauma or burns if all the upper extremities were involved and there is no unaffected extremity available for IV placement; orA need for long-term IV access (e.g., ESRD); orlymphedema or deep vein thrombosis (DVT) in the extremity of the IV (in the case where another extremity is not available); orCoagulopathy requiring blood thinning products; orArteriovenous (AV) graft or fistula in the extremity of the IV (in the case where another extremity is not available)Pregnancy-related conditions:Gestational age precluding completion of the Module by 36 weeks. A pregnant participant should complete visit 1 by gestational age 34 weeks, 0 days and complete Module 1 by week 36.Severe morning sickness limiting mixed meal tolerance test (MMTT) consumptionCertain types of disease states:Dumping syndrome or inability to consume 400 mL of liquidSevere malabsorption such as history of short gut syndrome or need for parenteral or enteral nutritionLess than 12-months post-metabolic or bariatric surgeryHistory of chronic pancreatitis (e.g., Cystic fibrosis) complicated by inability to tolerate 400 mL of fluidAnemia requiring chronic blood transfusions or iron infusionsAnemia defined as point of care (POC) Hemoglobin <9.5 g/dL at screeningSerious illness and in hospice or palliative care for terminal diseaseSwallowing issuesSelf-reported difficulty tolerating solids or liquidsAspiration risks that require change in thickness of liquid or dietary modificationsActive antibiotics use for an ongoing acute infectionAny disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's and/or team's opinion jeopardizes the safety of the participant or others or would interfere with adherence to the protocol.Module 2Any change to the participant's status from the time of All of Us enrollment that would render them ineligible for All of Us (e.g., being incarcerated, no longer living in the United States, or withdrawn from that study)Inability to provide informed consent and engage in informed consent proceduresInability or failure to complete all critical elements from Module 1 (dietary, physical activity and sleep assessments, continuous glucose monitoring, MMTT)Participants who are already enrolled in Module 3Participants who are unlikely to be able to adhere to the protocol, based on structured adherence assessment by a study registered dietitian or other trained staff. This includes participants who have known allergic reactions to, or unwillingness to consume, study foods in Module 2 (e.g., gluten, meat, fish, dairy products) that cannot be reasonably accommodated by the metabolic kitchen within allowable criteria for the test diets.Participants who plan to relocate to an area not served by NPH or travel plans that do not permit completion of the Module 2 study over a continuous period of approximately 10 to 12 weeksPregnancy-related conditions:Gestational age precluding completion of the Module by week 36. A pregnant participant must be able to begin the first dietary intervention by gestational age 26 weeks, 0 days and complete the Module by week 36.High risk pregnancy defined as fetal anomaly, gestational hypertension (SBP >140 mmHg and DBP >90 mmHg), pre-eclampsia, or gestational diabetes mellitusPossible ethanol (alcohol) use disorder defined by Alcohol Use Disorders Identification Test (AUDIT) score of >15History of surgery for the treatment of obesity and:Self-reported dumping syndrome; orFollowing a special diet prescribed by their practitionerUncontrolled disease states:Hypertension >160/100mmHgExacerbation of underlying gastrointestinal disease, including inflammatory bowel disease or other malabsorptive disordersDecompensated cirrhosisDiabetes Mellitus with HbA1c >12% at screeningNewly diagnosed diabetes within the past three months or diagnosed diabetes mellitus at screening (HbA1c >6.5%)Participants with a history of end-stage renal disease (ESRD) on hemodialysisActive infectious diseases (e.g., active tuberculosis < 3 months from symptom onset or positive test, COVID < 1 month from symptom onset or positive test)Malignancy (e.g., cancer) actively receiving cytotoxic chemotherapy (oral or infusions) treatment except for nonmelanoma skin cancers during the study periodParticipants who require dietary restrictions due to a medical condition or are on a prescribed diet for underlying chronic diseasesParticipants with Type 1 or Type 2 diabetes on insulinParticipants aged ≥ 75 years with Type 2 diabetes taking prescribed medications that can cause hypoglycemia (e.g. sulfonylureas, glinides), or on a prescribed dietHospitalization for a chronic disease (e.g., congestive heart failure, stroke) within the past three monthsRequiring transfusions/apheresis during study periodParticipants with a current diagnosis of, or who have received treatment for, bulimia or anorexia nervosa within the past 3 yearsParticipants with major psychiatric disorders, including major depression, schizophrenia, or psychosis, who have been hospitalized in the past six (6) months or are currently enrolled in treatment programsAnemia defined as point of care (POC) Hemoglobin <9.5 g/dL at screeningMyocardial infarction, invasive cardiac procedure, participation in a cardiac or acute rehabilitation programs, transient ischemic attacks, or unstable arrhythmias within the past 3 monthsAny disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's opinion, might jeopardize the safety of the participant or others, or be expected to interfere with adherence to the protocol.Module 3All the above mentioned exclusion criteria for Module 2Participants who are already enrolled in Module 2Any disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's opinion, might jeopardize the safety of the participant or others, or would interfere with adherence to the protocolInability to abstain from tobacco or nicotine use, vaping, alcohol, illicit drug use, or recreational drug use for two (2) consecutive weeks while domiciled in the clinical unit. Nicotine gum or patch are permitted.Any condition requiring in-person treatments or visits during the study period. This will not be accommodated by the domiciling protocol; however, tele-health visits with the participants regular doctor are permitted.Lactation or other infant care needs that cannot be accommodated while domiciled in the clinical unitDepression as assessed by:Patient Health Questionnaire (PHQ-9) score ≥ 15; orAffirmative answer to PHQ-9 suicidality question: "Thoughts that you would be better off dead or of hurting yourself in some way"Unable to engage in daily self-care activities (e.g., bathing, transferring, toileting, feeding, dressing)Uncontrolled endocrine disorders (such as Cushing's disease, pituitary disorders, diabetes)Uncontrolled pain requiring frequent or daily treatment, or adjustment of medication requiring weekly or bi-weekly visits. Pain medications used on an as-needed basis (PRN), such as acetaminophen or NSAIDs, are not excluded.Chronic prescription medications that would pose logistical and safety issues for participation