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THE CENTER WITHIN · EVIDENCE LIBRARY

Root-cause, systems-based, lifestyle-centered care

Functional Medicine

C – Emerging10 verified peer-reviewed articles

WHAT THE RESEARCH SHOWS

Functional medicine is a care model rather than a single treatment. It combines individualized assessment with nutrition, sleep, movement, stress and relationship interventions. That makes it harder to study than a single therapy, and most literature is editorial or narrative. The best outcome data come from Cleveland Clinic. A 2019 JAMA Network Open study of 7,252 patients found functional medicine care was associated with greater improvements in PROMIS global physical health at 6 months than primary care. A 2021 BMJ Open study found group (shared medical appointment) delivery improved physical and mental health more than individual visits and cost less. Smaller cohorts report improvements in inflammatory arthritis, IBD and Gulf War Illness. For longevity, a pilot RCT of an 8-week diet, sleep, exercise and relaxation program was associated with a 3.23-year reduction in epigenetic (DNA-methylation) age versus controls. The finding is intriguing but small and needs replication.

the studies,

READ THE EVIDENCE

10 of 10 studies

C – EmergingFunctional medicine associated with better quality of life (Cleveland Clinic, 7,252 patients)Retrospective cohort, propensity-matched · Tension / well-being

IN PLAIN LANGUAGE

In a large study at Cleveland Clinic, patients seen in the functional medicine center reported greater improvements in overall physical health after six months than similar patients in primary care.

Study type
Retrospective cohort, propensity-matched
Who was studied
7,252 adults (1,595 functional medicine; 5,657 family health center)
Outcome area
Tension / well-being
Key finding
At 6 months, functional medicine patients had significantly larger improvements in PROMIS global physical health than propensity-matched primary care patients (P = .004).
Evidence grade
C – Emerging
Limitations
Retrospective; 12-month comparison not significant in the full matched sample; modest effect size.
Citation
Beidelschies M, Alejandro-Rodriguez M, Ji X, Lapin B, Hanaway P, Rothberg MB. Association of the Functional Medicine Model of Care With Patient-Reported Health- Related Quality-of-Life Outcomes. JAMA Netw Open. 2019;2(10):e1914017.
PubMed 31651966DOI 10.1001/jamanetworkopen.2019.14017
C – EmergingGroup functional medicine visits improved outcomes and cost lessRetrospective cohort, propensity-matched · Tension / well-being

IN PLAIN LANGUAGE

Functional medicine delivered in small groups improved physical and mental health more than one-on-one visits, and cost less to deliver.

Study type
Retrospective cohort, propensity-matched
Who was studied
213 matched pairs with chronic conditions
Outcome area
Tension / well-being
Key finding
Shared medical appointments produced greater improvements in PROMIS physical and mental health and more weight loss than individual visits. Both groups improved systolic BP by 5.5 mm Hg. Shared visits cost less to deliver.
Evidence grade
C – Emerging
Limitations
Retrospective; single center.
Citation
Beidelschies M, Alejandro-Rodriguez M, Guo N, et al. Patient outcomes and costs associated with functional medicine-based care in a shared versus individual setting for patients with chronic conditions: a retrospective cohort study. BMJ Open. 2021;11(4):e048294.
PubMed 33849860DOI 10.1136/bmjopen-2020-048294
C – EmergingDiet and lifestyle program associated with lower epigenetic age (pilot RCT)Pilot randomized controlled trial (8 weeks) · Longevity marker (epigenetic age)

IN PLAIN LANGUAGE

In a small randomized pilot, an 8-week diet and lifestyle program, including relaxation practice, was linked to a lower "biological age" on an epigenetic clock. Larger studies are needed to confirm this.

Study type
Pilot randomized controlled trial (8 weeks)
Who was studied
43 healthy men aged 50–72
Outcome area
Longevity marker (epigenetic age)
Key finding
The program (diet, sleep, exercise, relaxation, probiotics, phytonutrients) was associated with a 3.23-year decrease in Horvath DNA-methylation age versus controls (p = 0.018).
Evidence grade
C – Emerging
Limitations
Small pilot; men only; no-intervention control. Two corrections published (PMIDs 35907207, 38488762).
Citation
Fitzgerald KN, Hodges R, Hanes D, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021;13(7):9419-9432.
PubMed 33844651DOI 10.18632/aging.202913
C – EmergingFunctional medicine health coaching improved elimination-diet adherence (RCT)Randomized controlled trial (10 weeks) · Tension / well-being

IN PLAIN LANGUAGE

Adding virtual functional medicine health coaching to an elimination diet helped people stick to it. People with more symptoms saw greater improvements in mental health.

Study type
Randomized controlled trial (10 weeks)
Who was studied
125 healthcare professionals
Outcome area
Tension / well-being
Key finding
Both arms improved. There was no between-group difference overall, but among more symptomatic participants, coaching improved PROMIS mental health and symptom scores more than self-guided care.
Evidence grade
C – Emerging
Limitations
Primary comparison not significant; relatively healthy sample. An erratum was published (PMID 38669437).
Citation
D'Adamo CR, Kaplan MB, Campbell PS, et al. Functional medicine health coaching improved elimination diet compliance and patient-reported health outcomes: Results from a randomized controlled trial. Medicine (Baltimore). 2024;103(8):e37148.
PubMed 38394515DOI 10.1097/MD.0000000000037148
D – InsufficientFunctional medicine for inflammatory arthritis (retrospective)Retrospective cohort (12 weeks) · Tension / pain

IN PLAIN LANGUAGE

People with inflammatory arthritis who added functional medicine to their standard care reported less pain and better physical health over 12 weeks.

Study type
Retrospective cohort (12 weeks)
Who was studied
54 patients with rheumatoid or psoriatic arthritis
Outcome area
Tension / pain
Key finding
Adding functional medicine to standard care was associated with significant reductions in pain and improvements in PROMIS physical health.
Evidence grade
D – Insufficient
Limitations
Retrospective; small; baseline differences between groups.
Citation
Droz N, Hanaway P, Hyman M, Jin Y, Beidelschies M, Husni ME. The impact of functional medicine on patient-reported outcomes in inflammatory arthritis: A retrospective study. PLoS One. 2020;15(10):e0240416.
PubMed 33031458DOI 10.1371/journal.pone.0240416
D – InsufficientFunctional medicine program improved sleep and fatigue in IBDSingle-arm cohort · Parasympathetic / sleep

IN PLAIN LANGUAGE

A small group of people with inflammatory bowel disease reported better sleep, less fatigue and better quality of life after a functional medicine program that addressed nutrition and stress.

Study type
Single-arm cohort
Who was studied
19 patients with IBD (15 completers)
Outcome area
Parasympathetic / sleep
Key finding
A 5-visit program with a 6-week elimination diet and lifestyle sessions (including stress) improved fatigue, sleep quality, IBD quality of life and symptoms (all P < .001).
Evidence grade
D – Insufficient
Limitations
Very small; no control group.
Citation
Strobel TM, Nguyen C, Riggs T, et al. Functional Medicine Approach to Patient Care Improves Sleep, Fatigue, and Quality of Life in Patients With Inflammatory Bowel Disease. Crohns Colitis 360. 2022;4(3):otac032.
PubMed 36777428DOI 10.1093/crocol/otac032
D – InsufficientVirtual functional medicine program for Veterans with Gulf War Illness (VA pilot)Clinical pilot, pre–post · Tension / well-being

IN PLAIN LANGUAGE

A VA pilot program delivering functional medicine by telehealth, similar to TCW's virtual model, was well attended and linked to better physical and mental health and sleep in Veterans with complex illness.

Study type
Clinical pilot, pre–post
Who was studied
Combat-deployed Veterans with chronic multisymptom illness
Outcome area
Tension / well-being
Key finding
A 6-month telehealth program (functional medicine assessment, nutrition and exercise coaching, mindfulness, yoga) was associated with improvements in physical and mental health symptoms and sleep quality.
Evidence grade
D – Insufficient
Limitations
Pilot; no control group.
Citation
Haws K, Mak S, Greer S, et al. A Virtual Functional Medicine-Based Interdisciplinary and Integrative Intervention for Gulf War Illness. Mil Med. 2024;189(Suppl 3):99-105.
PubMed 39160805DOI 10.1093/milmed/usae054
C – EmergingFunctional medicine vs usual care in type 2 diabetes: no significant difference (balancing)Open-label randomized pilot (24 months) · Longevity marker (metabolic)

IN PLAIN LANGUAGE

In a small randomized trial, adding functional medicine to diabetes care did not lead to better blood sugar or quality of life than standard care. It is included for balance.

Study type
Open-label randomized pilot (24 months)
Who was studied
71 adults with type 2 diabetes on insulin
Outcome area
Longevity marker (metabolic)
Key finding
Adding functional medicine did not significantly improve glycemic, metabolic or quality- of-life outcomes compared with usual endocrinology care.
Evidence grade
C – Emerging
Limitations
Small; high dropout; pilot design.
Citation
Eldib M, Hatipoglu B, Beidelschies M, et al. A functional medicine approach to diabetes control and quality of life: an open-label randomized pilot study. J Clin Transl Endocrinol. 2026;44:100437.
PubMed 41953254DOI 10.1016/j.jcte.2026.100437
Not graded (review)Review: integrative approach to HPA-axis (stress system) dysfunctionNarrative review · Mechanisms

IN PLAIN LANGUAGE

Published in The American Journal of Medicine, this review explains how the body's central stress system can become dysregulated, and how integrative and functional approaches aim to restore balance.

Study type
Narrative review
Who was studied
Not applicable
Outcome area
Mechanisms
Key finding
Summarizes how chronic stress, diet, circadian disruption and environmental exposures affect the HPA axis, and reviews integrative strategies including mind-body therapies and lifestyle interventions.
Evidence grade
Not graded (review)
Limitations
Narrative, not systematic.
Citation
Ring M. An Integrative Approach to HPA Axis Dysfunction: From Recognition to Recovery. Am J Med. 2025;138(10):1451-1463.
PubMed 40499704DOI 10.1016/j.amjmed.2025.05.044
Not graded (review)Review: measuring outcomes in functional medicine with PROMISReview · Methods

IN PLAIN LANGUAGE

This paper explains how functional medicine practices can use a validated NIH questionnaire (PROMIS) to track patient progress, a practice TCW can adopt to build its own outcome data.

Study type
Review
Who was studied
Not applicable
Outcome area
Methods
Key finding
Describes how the NIH-validated PROMIS Global measure can track physical, mental and social well-being in functional medicine care and research.
Evidence grade
Not graded (review)
Limitations
Methods paper.
Citation
Beidelschies M, Cella D, Katzan I, D'Adamo CR. Patient-Reported Outcomes and the Patient-Reported Outcome Measurement Information System of Functional Medicine Care and Research. Phys Med Rehabil Clin N Am. 2022;33(3):679-697.
PubMed 35989058DOI 10.1016/j.pmr.2022.04.008

EDUCATIONAL DISCLAIMER

This library is for educational purposes and is not medical advice. Individual results vary. Consult a qualified provider before starting any new therapy. Citations were verified against PubMed on September 25, 2026.

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