**7. Interactions summary**

The combination of several dietary ingredients might be desirable when their main mechanisms of action and clinical effects differ. For example, combination of an anti-inflammatory, antiviral, immunostimulant, and bronchodilator herbs might be recommended. Safety combination of black seed and turmeric has been demonstrated in a clinical study. *N. sativa* seed (1.5 g/d) and turmeric (2.4 g/d) in patients with metabolic syndrome for 4 weeks was safe and effective in reducing blood glucose, cholesterol, and blood pressure despite both ingredients having hypoglycemic and antihypertensive effects alone [115]. Any effect of echinacea on blood glucose and blood pressure is insufficient to evaluate. Licorice can increase blood pressure depending on the dose. Since turmeric and *N. sativa* have anti-hypertensive effects, the addition of licorice might be safe. All of the four dietary ingredients described here inhibit CYP2C9. All except *N. sativa* also inhibit CYP1A2. Turmeric and licorice also inhibit CYP2B6. Turmeric inhibits CYP3A4 and echinacea induces


#### **Table 2.**

*Summary of level of evidence for efficacy and safety of echinacea, licorice, turmeric, and black seed in COVID-19, heart disease, and diabetes.*

it. Thus, caution should be taken when combining these dietary ingredients with drugs metabolized by CYP3A4, 2C9, 1A2 and 2B6. As presented in **Table 1**, many drugs used in COVID-19, diabetes, and heart disease are metabolized by CYP3A4 and 2C9. Caution should be taken with echinacea and turmeric because they induce or inhibit CYP3A4, respectively. Lastly, many drug examples presented in **Table 2** are excreted via urine. Turmeric and black seed are likely safe when combined with medications that are excreted by the kidneys. Caution when combining with licorice due to its potential to cause hyperkalemia. No sufficient evidence to evaluate echinacea's effect on kidney function.
