Table A1.

Description of included studies and assessment of methodological quality according to Jadad scoring [45].

Study/ Registry	Echinacea Species	Control	Extraction Method	Supplement	Duration of Treatment/Observation	Daily Dose/Amount of Echinacea [mg]	Participant Number (N, ITT)	Age [Years]	Cold Definition	Jadad Score [18]
Bendel R et al., 1988 [20]	EPAr + EPUr Esberitox	NT	Ethanolic Extract	Thuiae occid, Baptisia	50 days in addition to Chemotherapy Prevention	3 × 50 drops	50	>18	Respiratory Infection induced Stop of Chemotherapy medically confirmed	2
Bendel R et al., 1989 [19]	EPAr + EPUr Esberitox	NT	Ethanolic Extract	Thuiae occid, Baptisia	12 Chemotherapy Cycles à 14 days Prevention	3 × 25 drops	67	>18	Respiratory Infection induced Stop of Chemotherapy medically confirmed	1
Bräuning B et al., 1992 [36]	EPUr	Placebo	Ethanolic Extract	None	Therapy 8–10 days	Dosis 1 = 90 drops/450 mg Dosis 2 = 2 × 90 drops/900 mg	180	18–60	Flu-like Infections, clinically confirmed (virally vs. bacterial)	1
Cohen HA et al., 2004 [18]	EPU + EAN	Placebo	Glycerol extract	Propolis + Vitamin C	3 mts Prevention	2–4 × 5–7.5 mL 500–1500 mg	328	1–5	Patient reported- medically confirmed	4
Forth H, Beuscher N, 1981 [17]	EPAr + EPUr (Esberitox)	Placebo (20 mg Vit C)	Ethanolic extract	Thuiae occid, Baptisia	3 × 14d cycles for up to 17 weeks Prevention	3 × 25 drops or 3 × 1 tablet	95	>18	Patient reported Rhinitis	1
Freyer HU, 1974 [22]	EPAr + EPUr	NT	Ethanolic extract	Thujae occid, Baptisia	6 weeks Prevention	3 × 20 drops	284	6–17	“infections” not further described	1
Goel V et al., 2004 [38]	EPU	Placebo	Ethanol	None	7 days Therapy	1st day: 10 × 4 mL 6 days: 4 × 4 mL	128 ≥2 colds/y	18–65	Patient reported Confirmed by study nurse/physician	5
Grimm (1999)/Schoeneberger (1996) [23,62]	EPUh	Placebo	Pressed-juice	None	2 mts Prevention	2 × 4 mL 6200 mg 2)	108 ≥3 colds/y	>11	Patient reported- Confirmed by physician	5
Hall, H et al., 2007 [24]	EPUh	Placebo	Pressed Juice	none	28 days Prevention	4 × 2 capsules/8000 mg	32	>17	Incidence of URTI Patient-reported outcome	4
Helbig (1961) [25]	EPUr + EANr (Esberitox)	NT	Ethanolic extract	Thujae occid/Baptisia	1 mt Prevention	3 × 20 drops	644	1–3	Infections of Upper Respiratory Tract	0
Jawad et al., 2012 [26]	EPU h + r (Echinaforce)	Placebo	Ethanolic extract	None	4 mts Prevention	3–5 × 0.9 mL 2.7–4.5 mL 2400–4000 mg	717	>17	Patient reported–confirmed by Jackson method Virally confirmed infections	5
König D, 1999 or Berg A (1998) [21]	EPUh	Placebo/Magnesium	Pressed Juice i.c. placebo and Biomagnesin	None	28 days Prevention	3 × 40 drops/8000 mg	42 (Athletes)	>17	Incidence of URTI Infection, Training failures	3
Kolev E et al., 2022 [27]	EPU h + r (Echinaforce)	NT	Ethanolic extract	None	5 months Prevention	3–5 × 2 tablets (400 mg)/2400–4000 mg	119	18–75	Patient reported, physician and virally-confirmed infections	2
Melchart (1998) 3-arm study [15]	EPUr	Placebo	Ethanolic extract	None	3 mts Prevention	2 × 50 drops 1800 mg 3)	99 (90 placebo) =/>3 colds/y	18–65	Patient reported- Confirmed by physician	4
Melchart (1998) 3-arm study [15]	EANr		Ethanolic extract	None	3 mts Prevention	2 × 50 drops 1800 mg 3)	100 (90 placebo)	18–65	Patient reported- Confirmed by physician
O’Neil J et al., 2008 [28]	EPU	Placebo	Dried Echinacea, not specified	None	8 weeks Prevention	3 × 2 capsules/1800 mg	90	18–65	Patient reported- Study staff confirmed	4
Ogal M et al., 2021 NCT02971384 [14]	EPU h + r (Echinaforce)	Placebo (VitC)	Ethanolic extract	None	4 months Prevention	3–5 × 1 tablet (400 mg)/1200–2000 mg	203	4–12	Patient reported, physician and virally-confirmed infections	5
Awad OG, 2020 2015NBA5732814 [29]	EPU root	Azithromycin (AZT) vs. NTC	Powder	None	6 × 10 days over 6 months Prevention	3 × 5 mL (250 mg)/1500 mg + AZT I.c. no prevention/ATZ prevention	300	5–16	Recurrent tonsillitis, reported by parents	1
Schmidt U et al., 1990 [30]	EAN	Placebo	Ethanolic extract	Eupatorium/Baptisia	2 month Prevention	1 × 12 mL/1440 mg 1)	609	>17	Patient reported- Confirmed by physician	4
Schulten B et al., 2001 [40]	EPUh (Echinacin®)	Placebo	Pressed Juice	None	10 days Therapy	2 × 5 mL (7750 mg)	80	>17	Patient reported confirmed by Jackson method (full picture of cold)	3
Spasov AA et al., 2004 [41]	EPUh	NT (standard therapy)	Pressed Juice	None (i.a. std treatment)	10 days Therapy	3 × 10 drops	80	4–11	Patient reported, Physician confirmed uncomplicated RTIs	2
Sperber SJ et al., 2004 [31]	EPUh Echinaguard	Placebo	Pressed juice	None	14d Prevention	3 × 2.5 mL	46	18–65	Artificially Rhinovirus Infection, Jackson definition	3
Sumer J et al., 2023 [37]	EPU (h + r) (Echinaforce)		Ethanolic extract	None	10 days Therapy	1–5 tablets (3360 mg) or 2–7 sprays (1120 mg) 3360–16,800 mg	246	>17	Patient reported, physician and virally-confirmed flu-like infections	4
Tiralongo E et al., 2012 [32]	EPUr + EANr (MediHerb)	Placebo	Ethanolic extract	None	5–9 weeks Prevention	Priming dose 2 × 1 tabs followed by exposition dose 2 × 2 tabs sick dose 3 × 2 tabs/3825 mg and 7650 mg	148	18–65	Natural exposition (air travel)	5
Turner RB et al., 2005 [16] 4-arm study	EANr	Placebo	20% Ethanolic extract	None	7 days Prevention 5 days Therapy	3 × 1.5 mL (300 mg)/900 mg	206	>17	Artificially Rhinovirus Infection, Jackson definition Patient reported, physician and virally-confirmed flu-like infections	4
Turner RB et al., 2005 [16] 4-arm study	EANr	Placebo	60% Ethanolic extract	None	7 days Prevention 5 days Therapy	3 × 1.5 mL (300 mg)/900 mg	203	>17		4
Turner RB et al., 2005 [16] 4-arm study	EANr	Placebo	CO2 extract	None	7 days Prevention 5 days Therapy	3 × 1.5 mL (300 mg)/900 mg	196	>17		4
Turner RB et al., 2000 [33]	EPU	Placebo	Powder Almost no alkylamides	None	19 days (14 days prevention + 5 days therapy) Prevention	3 × 1 capsule/900 mg	92	>17	Artificial Rhinovirus Infection,	3
Taylor (2003)/Weber (2005) [35,42]	EPUh (Echinacin®)	Placebo	Pressed juice	None-	4/1 week Therapy	2 × 3.75–5 mL 7.5–10 mL 7500–10,000 mg	407/401	2–11	Study staff confirmed	5
Yakoot M et al., 2011 [43]	E (Immumax)	Placebo	Extract	Garlic, Nigella sativa, Panax ginseng, Vitamin C, Zinc	14 days Therapy	2 × 1 capsule (120 mg)/240 mg	63	38 (Mean)	Patient reported- Confirmed by physician	5
Zhang X et al., 2003 [34]	EPUr	Placebo	Powdered root	None	8 weeks Prevention	2 × 1 capsule (294 mg)/588 mg	111	18–65	Patient reported- Confirmed by physician	3

E…Echinacea (not further specified) EAN…Echinacea angustifolia. EPU…Echinacea purpurea. h…herb. r…root. NT…No-treatment control. ITT…Intention-to-treat. ¹⁾ with 120 mg/mL EA extract; ²⁾ product contains 22% Ethanol for stabilisation; ³⁾ at 20 drops / ml and δ = 0.9 gr/mL.