Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through F-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 
E
In-vitro studies
 
F
Theoretical based on biochemistry/physiology/pharmacokinetics
 

Introduction

Inflammatory marker testing provides crucial health insights, aiding diagnosis, monitoring, and treatment decisions. Inflammation manifests through various symptoms, from acute signs to chronic indicators, and can be organ-specific. These markers offer valuable information for conditions related to inflammation. Understanding the complex relationship between inflammation and these conditions is essential. (NIEHS 2023)(NLM 2021)(Pahwa 2023)

Labs

C-reactive protein

Elevated C-reactive protein (CRP), a marker of inflammation in the body, is important for detecting and monitoring inflammatory conditions. CRP levels rise in response to inflammation caused by infections, injuries, or chronic diseases, depicting the presence and severity of inflammation. (Nehring 2023)(Sproston 2018)

C-reactive protein in the Fullscript catalog

Erythrocyte sedimentation rate

Erythrocyte sedimentation rate (ESR) is a widely used blood test that measures the rate at which red blood cells settle in a tube, providing a non-specific indicator of inflammation. ESR testing is valuable for detecting and monitoring inflammatory conditions. (Alende-Castro 2019)

Erythrocyte sedimentation rate in the Fullscript catalog

Omega-3 index

This test measures omega-3 fatty acid levels, which play a crucial role in regulating inflammation in the body. A higher omega-3 index is associated with lower levels of inflammatory markers, such as CRP and interleukin-6 (IL-6), and reduces the risk of inflammatory-related diseases. (Calder 2010)

Omega-3 index in the Fullscript catalog

Homocysteine

Homocysteine enhances inflammatory responses and contributes to atherosclerosis and cardiovascular diseases. Elevated levels are associated with increased inflammatory markers, suggesting homocysteine acts as both a marker and mediator of inflammation in various pathological conditions. (Durga 2005)(Elsherbiny 2020)(Li 2015)(Mokgalaboni 2024)(Oudi 2010)(Tawfik 2021)(Zhang 2021)

Homocysteine in the Fullscript catalog

Vitamin B12, vitamin B6, and folate

Vitamins B12, B6, and B9 (folate) are crucial in regulating homocysteine levels, thus controlling inflammation. These vitamins act as cofactors in homocysteine metabolism, reducing the risk of hyperhomocysteinemia and its inflammatory effects on cardiovascular health, cognitive function, and cellular processes. (Bajic 2022)(Chiocchetti 2018)(Kataria 2021)(Zhang 2021)

Vitamin B12, vitamin B6, and folate in the Fullscript catalog

Cytokine response

Tumor necrosis factor (TNF) and interleukin testing are crucial for evaluating inflammation. These cytokines regulate immune responses and are linked to various inflammatory conditions. Testing aids in diagnosing, predicting disease severity, and monitoring treatment responses, particularly for anti-TNF therapies. (Khan 2023)(van Loo 2022)

Cytokine response in the Fullscript catalog

Iron panel with ferritin

Iron panel testing with ferritin and complete blood count (CBC) provides a comprehensive assessment of both iron status and inflammation. Ferritin, an acute-phase reactant, can be elevated in response to inflammation, which may obscure its role in reflecting true iron stores. Therefore, interpreting ferritin alone can be misleading; for instance, ferritin levels may appear normal or elevated due to inflammation, even when iron deficiency or anemia is present. Including an iron panel—such as total iron-binding capacity (TIBC)—and a CBC, can help gain a fuller picture and distinguish between true iron deficiency and inflammation-related elevations in ferritin. This comprehensive approach not only differentiates types of anemia but also aids in identifying conditions like hemochromatosis and can indicate disease severity in certain infections. (Banchini 2021)(Faruqi 2021)(Fertrin 2020)(Kell 2014)(Khan 2016) 

Iron panel with ferritin in the Fullscript catalog

Antioxidants (vitamins A, C, and E)

These antioxidants have significant anti-inflammatory properties. Vitamin C combats oxidative stress and reduces inflammatory markers. Vitamin E, especially α-tocopherol, benefits subclinical inflammation. Vitamin A supports immune function and mucosal barriers. Assessing these vitamins provides insights into antioxidant status and potential inflammatory processes, enabling targeted interventions when combined with other inflammatory markers. (Asbaghi 2020)(Crook 2022)(Ellulu 2015)

Antioxidants (vitamins A, C, and E) in the Fullscript catalog

Complete blood count (includes differential and platelets)

A CBC with differential provides a comprehensive view of immune function by analyzing white blood cell counts, detecting inflammation-associated anemia, and evaluating platelet counts. Key inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), can be derived from CBC results. The NLR indicates inflammation levels and prognosis in conditions like infections, while the PLR reflects pro-inflammatory states, particularly in cardiovascular diseases. The LMR reveals shifts in immune cell populations, with low values suggesting immune dysregulation. (Seo 2022)

 

Complete blood count in the Fullscript catalog

Dietary supplements

Inflammation can have both positive and health effects. Inflammation works with the immune system. However, when inflammation becomes chronic, it can impact health. (Chen 2017)(Proctor 2015)(Sharif 2021)

The following evidence-based dietary ingredients may help address inflammation.

Curcumin (Curcuma longa)

600–1,000 mg, total per day, minimum 8–10 weeks

  • Curcumin decreased CRP (-0.58 mg/l), TNF-α (-3.48 pg/ml), IL-6 (-1.31 pg/ml), and malondialdehyde (MDA) (-0.33 umol/l), and increased superoxide dismutase (SOD) activity (20.51 u/l) and total antioxidant capacity (TAC) (0.21 mmol/l). (A) Curcumin decreased CRP (-3.67 mg/l) and hs-CRP concentrations. (A)
  • Compared to placebo, curcumin decreased IL-6 by ~49%, TNF-α by ~63%, and MDA by ~38%. (B) (Dehzad 2023)(Gorabi 2022)(Usharani 2008)
Curcumin (Curcuma longa) in the Fullscript catalog

Omega-3 fatty acids (EPA/DHA)

2.5 g, total per day, minimum 12 weeks

  • Omega-3s moderately decreased serum CRP, as well as IL-6 and TNF-α with a smaller effect. (A) 
  • Compared to placebo, omega-3 supplementation decreased total serum cortisol by 19% and IL-6 levels by 33% during a stressful event, CRP by ~30%, IL-6 by ~22%, and TNF-α by ~16%. (B) (Flores 2020)(Kavyani 2022)(Madison 2021)
Omega-3 fatty acids (EPA/DHA) in the Fullscript catalog

Probiotics

1.6 × 109 CFU, total per day, minimum eight weeks

  • Prebiotics and probiotics support the intestinal microbiome, oxidative stress, and inflammation balance by increasing intestinal anaerobes and maintaining the integrity of the intestinal barrier. (A)
  • Compared to placebo, a multistrain synbiotic reduced TNF-α by ~6% and hs-CRP by ~10% in postmenopausal females. (B)
  • Compared to placebo, Lactobacillus rhamnosus GG reduced IL1-Beta and lipopolysaccharide concentrations by ~ 35% and ~30%, respectively. (C) (Lahiji 2021)(Lopes 2018)(Moludi 2021)
Probiotics in the Fullscript catalog

Quercetin

≥500 mg, total per day, minimum eight weeks

  • Quercetin had a large effect on decreasing IL-6 and a smaller effect on decreasing serum CRP. (A)
  • Quercetin decreased TNF-α and IL-6 in females. (B)
  • Compared to placebo, quercetin increased serum TAC by ~20%. (B) (Dehghani 2020) (Ou 2020)(Vaez 2022)
Quercetin in the Fullscript catalog

Disclaimer

The Fullscript Medical Advisory Team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
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