1. Description of interventions per condition.

Condition	Study	Brand	Manufacturer	Composition	Dosage, frequency and duration	Mode	Concomitant treatment
Asthma	Hosseini 2001a	Pycnogenol®	Horphag Research, Geneva, Switzerland.	Bioflavonoid mixture extracted from Pinus maritima.	1 mg/lb body weight/day (maximum 200 mg/day) for 4 weeks.	Not reported.	Usual medications could be used except for glucocorticoids, leukotriene antagonists, multivitamins, aspirin and any other NSAIDs.
	Lau 2004	Pycnogenol®	Horphag Research, Geneva, Switzerland.	Proprietary mix of water‐soluble bioflavonoids from French maritime pine (Pinus maritima/pinaster Aiton); broadly divided into catechin, epicatechin and taxifolin as monomers, and condensed flavonoids (procyanidins and proanthocyanidins).	1 mg/lb body weight in 2 divided dosages daily for 3 months.	Not reported.	Not reported whether specific medication was not permitted; however, change in use of rescue inhaler (albuterol) and oral medication Accolate (zafirlukast; leukotriene receptor antagonist) were reported as outcomes in the trial, therefore we know that these specifically were permitted.
Attention deficit hyperactivity disorder	Trebatická 2006	Pycnogenol®	Drug Research Institute, Modra, Slovakia.	French maritime pine (Pinus pinaster) consisting of phenolic acids, catechins, taxifolin and procyanidins.	1 mg/kg body weight at breakfast daily for 1 month.	Not reported.	None were permitted ‐ neither psychotropic drugs nor vitamins E and C supplements during the study period.
Cardiovascular disease and risk factors	Cesarone 2008	OPC‐3®	nutraMetrix, Division of Market America, Greensboro, NC, USA.	400 mg flavonoids (consisting of equal amounts of Pycnogenol®, grape seed, bilberry, citrus, and red wine); as well as inactive ingredients i.e. fructose, glucose, citric acid, potassium bicarbonate, silica, calcium sulfate, and pectin.	1x 10 g pouch daily for 2 months	Orally, following solubilization of sachet contents with 180 mL water resulting in an isotonic solution.	"...none of the subjects was on a medical intervention...".
	Drieling 2010	Flavangenol®	Toyo‐FVG, Toyo Bio‐Pharma, Torrance, California and Shinyaku Co, Ltd, Saga, Japan.	OPC extracted from the milled bark of Pinus pinaster (also known as Pinus maritime and Pinus maritimus); comprising approximately 40% proanthocyanidin oligomers, 42% other polyphenols and 18% other substances. This is compounded with excipients of palatinit sugar, caramel, sucrose, fatty acid ester, and calcium stearate.	50 mg 4x daily every morning for 3 months.	Oral.	Participants were queried about their use of dietary supplements and medications at screening and were asked to report any changes.
	Enseleit 2012	Pycnogenol®	Horphag Research (UK) Ltd, London, UK.	Proprietary bark extract of Pinus pinaster ssp. atlantica.	200 mg daily for 8 weeks with a 2‐week washout period.	Not reported.	Concomitant treatment: optimal standard cardiovascular therapy "The patients were advised not to take their usual drugs in the morning of the examination day...medical therapy was unchanged throughout the study."; participants on concomitant medication were as follows: aspirin 100%; statin 87%; ACE‐inhibitor/ARB 78%; beta blocker 74%; diuretics 35%; calcium‐antagonist 17%; clopidogrel 17%; ezetimibe 17%; oral anti‐diabetics 17%; marcoumar 4%; alpha‐antagonist 4%.
	Hosseini 2001b	Pycnogenol®	Cognis Corporation (LaGrange, Illinois, USA).	Proprietary bark extract of the French maritime pine tree (Pinus pinaster) containing flavonoids as monomers (catechin and taxifolin) and 85% as condensed polymers (including procyanidins) as well as phenolic acids, as minor constituents, and glycosylation products.	1 mg/lb body weight/day (maximum 200 mg/day) for 4 weeks.	Oral.	Usual medications could be used except for glucocorticoids, leukotriene antagonists, multivitamins, aspirin and any other NSAIDs.
	Liu 2004c	Pycnogenol®	Horphag Research Ltd.	Extract from the bark of the French maritime pine (Pinus pinaster Aiton), consists of a concentrate of polyphenols. Main constituents are procyanidins, pharmacologically active biopolymers composed from units of catechin and epicatechin. Additionally, containing the bioflavonoids catechin and taxifolin and a number of phenolic acids	100 mg for 12 weeks.	Oral.	After the 2‐week run‐in period on placebo, all participants were put on a calcium antagonist (nifedipine, sustained release tablets, 5 mg, Shanghai Pharmaceuticals Co, Ltd.) The dose nifedipine was 20 mg (frequency not reported, assumed to be daily) initially, and then adjusted at 2‐week intervals (either reduced or increased with 5 mg) as needed to sustain "stable blood pressure".
	Reule 2017	AbMIP (L‐arginine‐based multi ingredient product)	vasoLoges® protect, Dr. Loges & Co. GmbH, Germany.	4 tablets together containing 2400 mg L‐arginine, 80 mg Pycnogenol®, 45 μg vitamin K2, 10 mg alpha lipoic acid, 8 mg vitamin B6, 500 μg vitamin B12 and 600 μg folic acid.	2 tablets 2x daily (4 tablets) 4 weeks on experimental treatment or placebo, followed by a 8‐week washout period before cross‐over to treatment or placebo.	Oral.	No participants were on blood pressure medication, treatment for cardiovascular disease, or statins.
	Valls 2016	Oligopin®	Les Derivés Résiniques & Térpeniques (DRT, France).	Specific selective extraction and purification of French maritime pine bark (Pinus pinaster Aiton) resulting in a product with < 1% tannins and a high content of low molecular weight oligomeric procyanidins (> 70%) and ~ 20% dimers. Each capsule contains 280 mg of total content consisting of 75 mg Oligopin, 175 mg maltodextrin, and 30 mg magnesium stearate.	2x daily, 1 capsule in the morning and 1 in the afternoon; 1 week run‐in for dietary stabilisation followed by 5 weeks on experimental treatment or placebo, a 3‐week washout period before cross‐over to treatment or placebo for 5 weeks.	Oral, as the product is water‐soluble it could be taken before or after meals.	None.
Chronic venous insufficiency	Arcangeli 2000	Pycnogenol®	Not reported.	French maritime pine bark (Pinus maritima Lam.) containing bioflavanoids, catechin, phenolic acids and a large number of procyanidins.	100 mg 3x per day for 2 months.	Not reported; assumed to be oral.	Participants were not allowed to take drugs which act upon the cardiovascular system, diuretics, or analgesic and anti‐inflammatory combinations during the treatment period.
	Petrassi 2000	Pycnogenol®	Not reported.	French maritime pine bark extract (Pinus maritima) with main constituents being phenolic compounds (catechin, epicatechin and taxifolin), condensed flavonoids (procyanidins/proanthocyanidins), and phenolic acids.	100 mg 3x per day for 2 months.	Oral.	During the 2‐month treatment period participants were not allowed to take drugs affecting the cardiovascular system, diuretics, analgesics or anti‐inflammatory compounds.
Diabetes mellitus	Belcaro 2006a	Pycnogenol® for all 3 treatment groups.	Horphag Research Management SA, Geneva, Switzerland.	Extract of bark from the French maritime pine.	Group 1 3x daily for 6 weeks 50 mg capsule orally together with 100 mg powder from 2x 50 mg capsules placed on ulcerated area.	Group 1 oral and local on ulcerated area.	All participants received general ulcer care daily that included washing and cleaning in water and a mild disinfectant (Citrosil, Italy), drying with soft paper tissue and dressed with nonallergic paper and a elastic‐adhesive bandage (Tensoplast, South Africa).
					Group 2 Once daily for 6 weeks 100 mg powder from 2x 50 mg capsules placed on ulcerated area.	Group 2 local on ulcerated area only.
					Group 3 3x daily for 6 weeks 50 mg capsule.	Group 3 oral only.
	Chous 2016	DiVFuSS	ZeaVision, LLC, Chesterfield, Missouri, USA.	Each capsule containing vitamins C, D3, and E (d‐alpha‐tocopherol), zinc oxide, eicosapentaenoic acid, docosahexaenoic acid, alpha‐lipoic acid (racemic mixture), coenzyme Q10, mixed tocotrienols/tocopherols, zeaxanthin, lutein, benfotiamine, N‐acetyl cysteine, grape seed extract, resveratrol, turmeric root extract, green tea leaf, and French maritime pine bark extract (Pycnogenol®, Horphag Research, Geneva, Switzerland).	2x capsules daily for 6 months.	Oral.	With the exception of a single, daily multivitamin and mineral supplement (23 of 67 participants), no participants were currently using dietary supplements containing ingredients found in the test formula.
	Domanico 2015	Diaberet	Visufarma, Rome, Italy.	Each tablet containing 50 mg Pycnogenol®; 30 mg vitamin E; and 20 mg Coenzyme Q.	1x tablet daily for 6 months.	Oral.	Single type of oral metformin monotherapy at a dose of 1000 mg 2x daily for the duration of the study and at least 6 months before enrolment.
	Liu 2004a	Pycnogenol®	Horphag Research Ltd.	French maritime pine (Pinus pinaster Aiton) bark extract with main constituents oligomeric procyanidins. Monomeric catechin, taxifolin, and various phenolic acids are also present.	100 mg for 12 weeks.	Oral.	Conventional oral antidiabetic medication as needed was permitted.
	Steigerwalt 2009	Pycnogenol®	Manhattan Drug Company, Inc., New York, USA.	French maritime pine bark extract.	3x 50 mg tablets per day after breakfast for 2 months.	Oral.	Not reported, but control of blood glucose levels by oral antidiabetic medication was part of the inclusion criteria and thus permitted.
	Zibadi 2008	Pycnogenol®	Not reported.	Extract from the bark of French maritime pine (Pinus maritima), mainly comprising phenolic compounds (catechin, epicatechin and taxifolin) and flavonoids (procyanidins).	25 mg tablets 5x per day for 12 weeks.	Oral.	1st generation sulphonylureas, 2nd generation sulphonylureas, metformin, and thiazolidinediones for glucose control were permitted.
Erectile dysfunction	Cai 2013	IDIProst® Gold	Not reported.	Each capsule contained Serenoa repens (320 mg), Crocus sativus (100 mg) and Pinus massoniana (120 mg).	1x 950 mg capsule per day for 3 months.	Oral.	None.
	Duracková 2003	Pycnogenol®	Not reported.	French maritime pine (Pinus pinaster) bark extract. Mixture of flavonoids as catechin, taxifolin, and procyanidins. Minor constituents: phenolic acids.	2x 20 mg pills 3x per day (total of 120 mg/day) for 3 months.	Oral.	None permitted (also no vitamin C and E supplements).
	Ledda 2010	Prelox®	Horphag Research UK Ltd, London, UK.	Each tablet contained 20 mg Pycnogenol®, 700 mg L‐arginine aspartate.	4x tablets daily, 2 tablets in the morning after breakfast and another 2 after dinner for 6 months.	Not reported.	No participants were taking antihypertensive medication before enrolment or during the trial; none had cholesterol medication either.
Female sexual dysfunction	Bottari 2012	Lady Prelox®	Horphag Research.	Each capsule contained 20 mg Pycnogenol®, 200 mg L‐arginine, 200 mg L‐citrulline, 50 mg Rosvita rosehip extract.	2x capsules in morning and 2x in evening for 8 weeks.	Oral.	"No medications or other supplements were permitted during the trial period, with the exception of daily vitamins and minerals."
Osteoarthritis	Belcaro 2008a	Pycnogenol®	Manhattan Drug Company Inc., New York, USA.	Extract of French maritime pine bark. Concentrate of plant polyphenols, predominantly procyanidins.	50 mg capsule 2x per day (after breakfast and dinner) for 3 months.	Oral.	Associated treatments prescribed by the participant's general practitioner were to be reported in a diary. After contacting the study authors we learned that NSAIDs, paracetamol and ibuprofen were allowed during the study.
	Cisár 2008	Pycnogenol®	Manhattan Drug Company, New York, USA.	French maritime pine (Pinus pinaster) bark extract consisting of a concentrate of polyphenols, several phenolic acids, catechin, taxifolin, and procyanidins.	50 mg tablets 3x per day with meals for 12 weeks.	Oral.	Participants could use NSAIDs or other analgesics prescribed prior to the start of the study and could change the dose and frequency of drug intake, but they had to report changes at each visit.
	Farid 2007	Pycnogenol®	Horphag Research Ltd, Geneva, Switzerland.	Extract from the bark of French maritime pine (Pinus maritima) containing monomeric phenolic compounds (catechin, epicatechin and taxifolin), condensed flavonoids (procyanidins), and phenolic acids.	50 mg tablets 3x per day for 3 months.	Oral.	COX‐2 and other NSAIDs as medical treatment for pain in the target knee.
Osteopenia	Panahande 2019	Oligopin®	France Purextract (DRT) Co.	Oligopin® containing 50 mg French maritime pine (Pinus pinaster) bark extract consisting of procyanidins (67 ‐ 75%), catechin (4 ‐ 10%), taxifolin (0.5 – 4%), taxifolin glucoside (3 – 8%), f glucoside (4 – 10%), gallic acid (0.1 – 1%), protocatechuic acid (0.5 – 3%), caffeic acid (0.5 – 3%), p‐coumaric acid (0.3 – 2%), ferulic acid (1 – 5%), and other oligomers including monomeric and dimeric phenolic acids.	250 mg/day given as 5 capsules per day; 2 capsules after breakfast, 2 capsules after lunch and 1 capsule after dinner for 12 weeks.	Oral.	Not reported.
Traumatic brain injury	Theadom 2013	Enzogenol®	ENZO Nutraceuticals.	Pine bark extract from New Zealand‐grown Pinus radiata. Each capsule contained 500 mg Enzogenol pine bark extract; consisting of proanthocyanidins (average 84%), taxifolin (1 ‐ 2%), other flavonoids, phenolic acids and stillbenes (8% combined), including catechin, quercetin, myricetin, astringenin, gallic acid, ferulic acid, caffeic acid, protocatechuic acid, and carbohydrates (5 ‐ 10%).	2x capsules daily taken with a large glass of water in the morning (15 minutes before breakfast) for 6 weeks.	Oral.	Not reported, but "Possible contradiction with medication" cited as a reason for attrition in treatment group.

ACE: angiotensin‐converting enzyme
COX‐2: cyclooxygenase‐2
NSAID: non‐steroidal anti‐inflammatory drug