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 D-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
 

Whole person care is a person-centered approach to medicine. It goes beyond treating symptoms or isolated conditions, focusing on the interconnectedness of bodily systems and addressing a wide range of factors. These include biological makeup, behavioral habits, environmental factors, and a patient’s personal beliefs, values, and goals. By tailoring care to align with these unique aspects, healthcare providers can create highly personalized treatment plans that address not only physical health but also emotional and mental well-being.

This protocol aims to provide healthcare providers with practical suggestions for supplements and lifestyle strategies, helping them design personalized whole person care plans for patients looking to optimize their endothelial and vascular health.  

Evidence-based supplements support vascular and endothelial health by targeting inflammation, oxidative stress, lipid metabolism, and endothelial function. Key ingredients include anthocyanins, coenzyme Q10 (CoQ10), folic acid, omega-3 fatty acids, specialized pro-resolving mediators (SPMs), and vitamin C, each with clinically backed benefits for cardiovascular wellness. 

Lifestyle strategies are essential for vascular and endothelial health, complementing clinical interventions with nutrition, movement, and oral care. Eating a balanced diet, engaging in regular exercise, and maintaining oral health supports metabolic function, vascular integrity, and cardiovascular resilience. 

This flexible approach ensures a personalized and comprehensive care plan for optimal results.

Ingredients

Anthocyanins 

320 mg total per day for a minimum of four weeks (Li 2015)(Thompson 2017)(Zhu 2013) 

  • Anthocyanins are naturally occurring plant compounds that are responsible for the deep red, purple, and blue colors found in many fruits and vegetables. (Khoo 2017)
  • Anthocyanins are known for their anti-inflammatory and antioxidant properties. Studies have found that supplementing with anthocyanins may help reduce inflammatory markers, such as TNF-α, C-reactive protein (CRP), IL-6, and IL-1β, and antioxidant markers, such as total radical-trapping antioxidant parameter (TRAP) and ferric reducing antioxidant power (FRAP). (Li 2015)(Xu 2021)(Zhu 2013)
  • Anthocyanins have also been found to support endothelial function by increasing the responsiveness of blood vessels to changes in blood flow (i.e., ↑ flow-mediated dilatation (FMD)) and decreasing proatherosclerotic activity at the artery wall (i.e., ↓ sVCAM 1). (Weissgerber 2014)(Zhu 2011)(Zhu 2013)
  • Studies have also shown that supplementation with anthocyanins may help reduce the risk of blood clots. (Thompson 2017)
Anthocyanins In the Fullscript catalog

CoQ10

Minimum of 100–200 mg once per day for a minimum of 8–12 weeks (Fan 2017)

  • Coenzyme Q10, otherwise known as CoQ10 or ubiquinone, is a fat-soluble, non-essential nutrient that plays an important role in free radical scavenging. (Díaz-Casado 2019) 
  • CoQ10 has been shown to decrease inflammatory markers such as CRP, IL-6, and TNF-α. (Fan 2017)
  • Additionally, CoQ10 has also been shown to increase total antioxidant capacity (TAC) and reduce free oxygen radicals like malondialdehyde (MDA). (Sangsefidi 2020)(Yoo 2018)
  • These therapeutic properties are likely the mechanism by which CoQ10 improves FMD and endothelial function. (Gao 2012)
CoQ10 in the Fullscript catalog

Folic acid

Minimum of 5 mg total per day for a minimum of 12 weeks (Alian 2012)(Zamani 2023)

  • Folic acid, also known as folate and vitamin B9, is a water-soluble B vitamin that has the potential to improve endothelial dysfunction. (Stanhewicz 2017) 
  • It has been proposed that folic acid may reduce atherogenesis by improving glycemic control and decreasing oxidative stress (i.e., ↑ TAC and glutathione (GHS), and ↓ MDA levels), inflammation (i.e., ↓CRP), blood pressure, cholesterol, and homocysteine levels. (Asbaghi 2021 A)(Asbaghi 2021 B)(Zamani 2023)
  • Supplementation with folic acid has been associated with improved endothelial function as measured by improved FMD and decreased adhesion molecules (i.e., ↓ VCAM) and microalbuminuria (Alian 2012)(Zamani 2023)
Folic acid in the Fullscript catalog

Omega-3 fatty acids 

 2–4 g total of EPA/DHA per day for a minimum of 12 weeks (Hu 2019)(Sekikawa 2019)(Wang 2012) 

  • Omega-3 fatty acids, like EPA and DHA, are polyunsaturated fatty acids that are most commonly derived from oily fish. (Calder 2012) 
  • Supplementing with omega-3 fatty acids has been shown to decrease atherosclerotic progression and fasting serum triglyceride. (Kastelein 2014)(Sekikawa 2019)
  • In addition to their antilipidemic and antiatherosclerotic properties, omega-3 fatty acids have also been shown to decrease inflammation (i.e., ↓ hs-CRP, IL-6, TNF) (Guo 2022)(Mortazavi 2018) and improve endothelial function (i.e., ↑ FMD). (Wang 2012) 
Omega-3 fatty acids in the Fullscript catalog

Specialized pro-resolving mediators (SPMs)

1.5–6 g of active fractionated marine lipid concentrate per day (Schaller 2020)

  • SPMs, derived from omega-3 polyunsaturated fatty acids, accelerate inflammation resolution by reducing neutrophil infiltration, clearing apoptotic cells, enhancing phagocytosis, and promoting a pro-resolving macrophage phenotype. 
    • 18-hydroxyeicosapentaenoic acid (18-HEPE), derived from EPA, serves as a precursor to E-series resolvins, which help regulate immune responses and reduce inflammation. 
    • 17-hydroxydocosahexaenoic acid (17-HDHA) and 14-hydroxydocosahexaenoic acid (14-HDHA), both derived from DHA, are intermediates in the biosynthesis of D-series resolvins and maresins (MaR1, MaR2), respectively. These mediators enhance tissue protection, promote inflammatory resolution, and support tissue repair and regeneration. (Irún 2023)
  • A double-blind, placebo-controlled crossover trial in healthy volunteers found that enriched marine oil supplementation increased plasma SPM levels in a time- and dose-dependent manner, enhanced neutrophil and monocyte phagocytosis, and reduced leukocyte and platelet activation. Transcriptomic analysis showed significant immune and metabolic gene expression changes within 24 hours. These findings suggest that enriched marine oil supplementation boosts circulating SPM levels and modulates immune function, supporting its role in inflammation resolution. (Souza 2020)
  • Similarly, an open-label study in ten patients with peripheral artery disease (PAD) and ten healthy volunteers demonstrated that five days of marine oil supplementation increased total specialized pro-resolving lipid mediators, enhanced monocyte and neutrophil phagocytic activity, and reduced pro-inflammatory markers, with the strongest effects in patients with PAD. Monocyte-derived macrophages shifted toward a reparative phenotype, correlating with lipid mediator changes. (Schaller 2020)
Specialized pro-resolving mediators (SPMs) in the Fullscript catalog

Vitamin C

Minimum of 500–2,000 mg total per day for a minimum of two weeks (Ashor 2014)

  • Vitamin C (ascorbic acid) is an essential, water-soluble vitamin. (Lykkesfeldt 2014) It is well-known for its anti-inflammatory properties (i.e., ↓ CRP,  IL-6) (Ellulu 2015) and ability to reduce free radicals by donating electrons (i.e., ↓ MDA and ↑ sGHS). (Boonthongkaew 2021)(Tessier 2009)
  • A meta-analysis of 44 randomized controlled trials found that daily supplementation with more than 500 mg of vitamin C reduced endothelial dysfunction as measured by improved FMD, forearm blood flow (FBF), and pulse wave analysis (PWA). (Ashor 2014)
Vitamin C in the Fullscript catalog

Lifestyle recommendations

Dietary recommendations

 

Mediterranean-style diet (MD)

  • The macronutrient breakdown of the MD emphasizes a balance of healthy fats, moderate protein, and complex carbohydrates. Healthy fats, particularly from olive oil, nuts, and fatty fish, make up approximately 35–40% of total daily calories, with a focus on monounsaturated and omega-3 fats. Carbohydrates, primarily from whole grains, legumes, vegetables, and fruits, constitute around 45–60% of the diet, providing fiber and essential nutrients. Protein, derived from lean sources like fish, poultry, legumes, and dairy, contributes about 15–20% of the daily caloric intake, with limited consumption of red meat. This macronutrient profile supports cardiovascular health, promotes anti-inflammatory effects, and aids in metabolic regulation. (Ge 2020)(Willett 1995)
  • Meta-analyses reveal that the MD is associated with beneficial changes in biomarkers of metabolic dysfunction (e.g., body weight, BMI, waist circumference, glucose, insulin, HOMA-IR, advanced lipid profiles, hepatic function tests, and inflammatory markers). (Papadaki 2020) 
  • These biomarker changes are associated with a reduced intake of saturated fats, amino acids, and calories, and an increase in phytochemicals and gut microbiota-produced metabolites. (Tosti 2018)

Nitrate-rich foods

  • Dietary nitrates play a crucial role in cardiovascular health by enhancing nitric oxide (NO) bioavailability, which supports endothelial function and vasodilation, leading to improved blood flow and reduced blood pressure. Once consumed, nitrates are converted into nitrites and further reduced to NO in the body, aiding in oxygen delivery and vascular relaxation. They also exhibit anti-inflammatory and antioxidant effects by reducing reactive oxygen species (ROS) and preventing oxidative damage. Additionally, dietary nitrates inhibit platelet aggregation, lowering the risk of thrombosis and improving overall vascular health. (Machha 2012)
  • Dietary sources of nitrates include:
    • Leafy greens: Arugula, spinach, kale, Swiss chard, and lettuce
    • Root vegetables: Beets, radishes, and carrots (Brkić 2017)

Sulfur-rich foods

  • Hydrogen sulfide (H₂S) supports cardiovascular health by promoting vasodilation, improving circulation, and lowering blood pressure. It enhances NO bioavailability for better endothelial function and reduces inflammation by limiting leukocyte adhesion, suppressing cytokines, and inhibiting NF-κB activation. Additionally, H₂S acts as an antioxidant, reducing oxidative stress, and supports heart health through its anti-apoptotic and pro-angiogenic effects, protecting cardiomyocytes and aiding tissue repair. (Pan 2017)
  • The body synthesizes H₂S from sulfur-containing amino acids, making dietary intake of these precursors essential for maintaining optimal levels. Dietary sources of sulfur include:
    • Allium vegetables: Garlic, leeks, onions, scallions, and shallots
    • Cruciferous vegetables: Arugula, broccoli, Brussels sprouts, cabbage, cauliflower, kale, and radishes
    • Eggs
    • Legumes: Chickpeas, fava beans (broad beans), kidney beans, lentils, and peas
    • Meat and seafood: Chicken, crab, lobster, scallops, and organ meats 
    • Dairy products: Milk, yogurt, parmesan cheese, and cheddar cheese
    • Nuts and seeds: Almonds, brazil nuts, walnuts, sesame seeds, and sunflower seeds (Pathak 2014)(Doleman 2017)(Guo 2017)(Kim 2016)

Polyphenolic compounds 

  • Dietary polyphenols contribute to vascular health through multiple mechanisms, including vasodilation, antioxidation, anti-inflammation, and platelet regulation. They enhance endothelial function by increasing NO bioavailability, which relaxes blood vessels and improves circulation. Polyphenols, such as flavonoids, phenolic acids, and stilbenes, also act as antioxidants, neutralizing ROS and preventing oxidative stress, which is a major contributor to vascular dysfunction and atherosclerosis. Additionally, their anti-inflammatory properties help reduce endothelial damage by suppressing inflammatory cytokines and modulating immune responses. Some polyphenols, such as anthocyanins and flavan-3-ols, further inhibit platelet aggregation, lowering the risk of thrombosis and hypertension. (Grosso 2022) 
  • Dietary sources include:
    • Fruit: Apples, berries, black and green olives, and cherries
    • Nuts and seeds: Almonds and flaxseed meal
    • Leafy greens: Spinach
    • Legumes: Soybeans and soy products
    • Spices: Cloves
    • Other: Dark chocolate (Pérez-Jiménez 2010) 

Patient resources:

 

Oral hygiene 

  • Emerging research highlights the critical yet often-overlooked link between oral and cardiovascular health. 
  • A Japanese case-control study found that Streptococcus anginosus was significantly more abundant in the saliva and gut of stroke patients and was associated with a 20% higher risk of stroke. (Tonomura 2025) 
  • Additionally, the Atherosclerosis Risk in Communities (ARIC) study, a 25-year observational analysis of 6,000 US adults, linked flossing to significantly lower risks of ischemic and cardioembolic stroke and atrial fibrillation, independent of brushing and dental visits. (Sen 2025) 
  • Beyond infection and inflammation, oral nitrate-reducing capacity (NRC) may also play a key role in vascular function. The conversion of nitrate to nitrite by oral bacteria leads to nitric oxide formation, which has cardioprotective effects. (Rosier 2024)
  • Together, these findings suggest that daily flossing, along with other consistent oral hygiene practices—such as brushing twice daily, biannual dental visits, and reducing sugar intake—may support both oral and cardiovascular health.  

Patient resources:

 

Movement

  • Regular exercise is essential for cardiometabolic health, improving insulin sensitivity, cardiovascular function, weight management, and metabolism. Resistance training reduces visceral fat, lowers HbA1c, and supports diabetes management. (Yanai 2018) Aerobic exercise enhances oxygen delivery, reduces inflammation, and promotes blood vessel dilation while lowering blood pressure, LDL cholesterol, and triglycerides. (Pinckard 2019)(Westcott 2012)
  • Exercise also aids weight management by burning calories and preventing obesity. A 12-week trial showed that combining walking with a calorie-restricted diet led to greater weight loss than dieting alone. (Kleist 2017) Building muscle boosts metabolism, and high-intensity interval training (HIIT) increases post-exercise energy expenditure for hours. (Knab 2011)(McPherron 2013)(Wingfield 2015)
  • For heart health, aerobic and strength training improves oxygen uptake and left ventricular plasticity. (Howden 2018) Just 30 minutes of moderate exercise daily helps regulate blood pressure, triglycerides, and HDL cholesterol. (Dimeo 2012)(Wang 2017)(Zheng 2019) HIIT offers additional cardiovascular benefits, improving oxygen uptake, ventricular function, and endothelial health, especially for those with obesity or heart disease. (Batacan 2016)(Guiraud 2012)

Patient resources:

Disclaimer

The Fullscript Integrative 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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