Table 5.

Studies on complementary and alternative medicine in long COVID.

Source	Study Type	Country	Primary Aim	Sex (% Male)	Age Range (Years)	Total Pts (n)	Tested Dietary Supplement(s)	Results
Kharaeva et al. [153]	RCT	Russia	To alleviate PCS symptoms	49.7	35–69	213 (25 controls)	Fermented Carica papaya 14 mg per os and fermented Morinda citrifolia 14 mg per os Duration: 20 days	At 20 days, self-reported clinical symptoms as well as IL-6, IL-8, and nitric oxide metabolites diminished in PCS patients receiving supplementation compared to placebo. The PMNs capacity to phagocyte, AOA, and ATP content remarkably increased in the supplemented group compared to placebo.
Rossato et al. [154]	Open-label observational trial	Italy	To improve the general health status especially the PCS-related chronic fatigue	39.3	35–62	201	Vitamins D, H, B1, B3, B7, C, E 87 mg, minerals (e.g., iron, magnesium, zinc, selenium) 204 mg, amino acids (e.g., arginine, carnitine) 1.5 g, and Panax ginseng and Eleutherococcus senticosus extracts 150 mg, once daily per os Duration: 28 days	The scores on quality of life, health status, FACIT-Fatigue and mental fatigue significantly improved after the first 14 days and at 28 days.
Naureen et al. [155]	Pilot observational study	Italy	To diminish perceived PCS-related fatigue	47.5	28–76	40 (20 controls)	Vitamin C 160 mg; acetyl-L-carnitine 150 mg; hydroxytyrosol/olive polyphenols, 100 mg; thiamine 12.5 mg; vitamin B6, 5 mg; folic acid 0.2 mg; vitamin D3 0.025 mg; and vitamin B12. 0.005 mg, once daily per os Duration: 15 days	At 15 days, self-perceived energy doubled (+123%) and fatigue and tension levels halved (−51% and −48%, respectively) in the supplemented compared with the unsupplemented group.
Tosato et al. [156]	RCT	Italy	To increase physical performance, endothelial function and decrease persistent PCS-related fatigue	34.8	50.5 (median)	46	L-arginine, 1.66 g + liposomal vitamin C, 500 mg, BID, per os Duration: 28 days	At 28 days, 6 min walk distance, handgrip strength, and FMD increased significantly while self-reported fatigue was significantly lower in PCS patients belonging to the supplemented group compared with those receiving the placebo.
Belcaro et al. [157]	Pilot observational study	Italy	To ameliorate endothelial function, microcirculation inflammatory markers, and oxidative stress in PCS patients	NA	35–70	60	Pinus pinaster extract, 50 mg, 3 times a day (total 150 mg), per os Duration: 90 days	FMD, reactive finger hyperemia, ankle swelling rate, and renal cortical flow velocity improved significantly in the supplemented group after 1 month and after 3 months compared with controls. High-sensitivity CRP (hs-CRP), plasma Il-6 levels and oxidative stress markers decreased significantly over 3 months in the supplemented group. Questionnaire scores on quality of life, mood and fatigue, and Karnofsky scale performance index improved significantly in the supplemented group compared with controls after 1 and 3 months.
Bove et al. [158]	Pilot observational study	Italy	To improve cognitive function and psychosocial parameters in PCS patients	NA	65–68	40	Bacopa monnieri extract, 320 mg; L-theanine, 100 mg; Crocus sativus L. extract Saffron, 30 mg; vitamin B6, 9.5 mg; vitamin D, 25 µg; copper, 2 mg; biotin, 450 µg; folic acid, 400 µg; and vitamin B12, 33 µg, 1 capsule/day per os Duration: 90 days	After 90 days, functional status, assessed by the MMSE and PCFS scale, and major psychological disorders improved significantly.

PCS, post-COVID-19 syndrome; IL-6, interleukin-6; IL-8, interleukin-8; PMNs, polymorphonuclear leukocytes; AOA, antioxidant activity; FACIT, Fatigue: Functional Assessment of Chronic Illness Therapy—Fatigue Scale; FMD, flow-mediated dilation; NA, not available; CRP, c reactive protein; MMSE, Mini-Mental State Examination; PCFS, Post-COVID-19 Functional Status; PSQ, Perceived Stress Questionnaire; SRDS, Self-Rating Depression Scale.