Table 3. Descriptive data for clinical trials that have an intervention.

Citation	Objective of Study	Condition Group	Control	Results for outcome related to UPE	Author's Main Conclusion for Outcome of Interest	SIGN50 Criteria 1.1
Whole Body/Skin
Hagens et al. 2008	To qualify and validate UPE measurement following ultraviolet (UV) excitation of porcine and human skin to assess the potency of topical antioxidants. Some subjects were treated with antioxidant standard formulations of 0.25%, 0.5%, or 1% vitamin C on both inner forearms twice daily for 3 consecutive days. Others received Glucosylrutin twice daily for 7 consecutive days on both inner forearms.	Vitamin C study: 20 female volunteers (age range of 18–65 years); Glucosylrutin study: 23 male and female subjects (age range of 22–60 years)	C	Topical vitamin C treatment reduced UVA-induced UPE (intensity in counts x 103) in a dose dependent way. Reduction of the UPE signal, compared to control, was statistically significant for formulations containing 0.5% and 1% vitamin C. Topical treatment of skin with a formulation containing 0.25% a-glucosylrutin was also shown to significantly reduce UVA induced UPE. *****	UVA irradiation induces UPE, especially in deeper skin layers. Clinical data demonstrate UPE measurement following UV excitation is a reliable and valid method for the non-invasive measurement of antioxidant efficacy on skin. Thus, it can be assumed that reduction of UPE due to previous topical treatment with an antioxidant indicates a protection of living skin layers from pro-oxidative stress.	P
Raschke et al. 2004	To demonstrate the high in-vivo antioxidant capacity of 3% ascorbic acid.	27 (of 54) healthy female volunteers (age not reported)	P	The verum oil-in-water emulsion containing 3% ascorbic acid showed a significant reduction of UVA-triggered UPE compared to placebo. Vitamin C cream also exhibited a significantly stronger antioxidant potential (-75% change in UPE) than the verum containing 3% sodium ascorbyl phosphate (instead of ascorbic acid) in the same oil-in-water base (-51% change in UPE). The sodium ascorbyl phosphate emulsion showed no significant difference of UPE reduction compared to placebo (p = 20%) (-31% change in UPE). *****	Ascorbic acid is superior to sodium ascorbyl phosphate in an oil-in-water emulsion as a topical antioxidant for skin protection.	P
Jain 2010	To determine UPE decay characteristics of human skin and the modulatory influence of topically applied antioxidants. Six test areas were randomized on the back of the test subjects and measured.	12 healthy subjects with a mean age of 45.7+/−13.4 years (gender not reported)	C	UVA-induced UPE was characterized by two distinct decay phases: an initial 0–5 s burst approximately 80% of the complete signal with an inverse dose-response relationship, followed by a second decay phase showing a direct correlation. Antioxidant pretreatment caused a reduction in signal of about 50% during phase 1. The highest antioxidant efficacy (50%) was obtained with the smallest UVA dose of 126 mJ/cm2 (shortest irradiation time), whereas the difference in antioxidant efficacy obtained with 504 and 1008 mJ/cm2 of UVA was marginal(42 and 44%) *****	Sunscreens and antioxidants have different effects on cutaneous ROS generation. Sunscreens simply reduce the UVA intensity reaching the skin. As a result, cutaneous ROS generation does not depend on the irradiation time or UVA intensity, but on the applied UVA dose. Antioxidants do not just partly block UVA radiation, they also exert complex reactions with UVA-induced ROS, like resonance stabilization, and interact with other antioxidants or cutaneous enzymatic antioxidative systems as shown in this work by the modulation of the intersection point of decay curves at constant irradiation intensity. In summary, the data indicates that induced ultraweak photon emission of human skin is a sensitive, reliable, noninvasive method for studies of antioxidants or UVA filters.	A
Van Wijk 2010	To evaluate anti-oxidant activity of a specific topical OPCs formulation (anti-oxidant bioflavanoid) following UV exposure of the back of both left and right hands using the UPE assessment method. The authors hypothesized that the anti-oxidant effect of the OPCs cream would not only a) decrease skin UV-induced UPE but also b) protect the skin from sensitization to UV.	25 healthy female volunteers, age 19–68 years. Subjects with acne, eczema or hyper-pigmentation on the back of the hands were excluded. All subjects had Fitzpatrick skin type IV – VI.	U	The average level of spontaneous UPE from all subjects was 4.71+/−2.26 cps (min. 2.43 max.15.81 cps). Repeated left hand exposure to UV without treatment of OPCs cream demonstrated a steady increase in levels of UPE (statistically significant between recordings). However, topical OPCs cream applied to the right hand after UV resulted in a statistically significant decrease in UPE. *****	Results suggested a) that a reliable and valid protocol can be established to assess UV-induced oxidative stress in the skin, b) in vivo effects of topical antioxidants following exposure to UV can be demonstrated with non-invasive measurement of human UPE from skin and c) the topical OPCs cream investigated in this study can significantly reduce UV-induced UPE and protect skin from sensitization to UV.	W
Park 2009	To analyze the magneto-acupuncture stimuli effects on UPE of human hands.	45 healthy persons (29 men 16 women) 18–50 years of age. 8 subjects served as controls (Group 1), 4 subjects were treated with sham magnets (Group 2), and 33 subjects received treatment with magnets (Group 3).	U; P	UPE changes (counts per second) in control and sham groups were not significant. However, average and standard deviation UPE changes from the treatment group were evident in their palms. *	Average intensity and standard deviations for group 3 changed significantly compared with groups 1 and 2.	A
Blood Cells
Holzer et al. 2010	To characterize neutrophil phenotype and function at close intervals; pre-, intra-, and postoperatively, in uneventful partial hepatectomies.	14 (of 19) non-cirrhotic subjects with liver tumors undergoing liver surgery.	U	Spontaneous oxygen radical generation by neutrophils (measured by lucigenin enhanced UPE in counts per minute/neutrophil) was low 24 h preoperatively and had no significant differences compared to healthy volunteers (n = 5). 15 min after the release of the Pringle maneuver, spontaneous oxygen radical production by neutrophils peaked (p<0.05 vs. baseline). Afterwards, spontaneous oxygen radical production by neutrophils decreased again. ***	Activation of neutrophils during liver surgery may be detrimental because an increase in adhesive properties together with an increase in spontaneous oxygen radical production may result in tissue accumulation of neutrophils and subsequent tissue damage, especially to the liver remnant. Spontaneous production of oxygen radicals peaked sharply 15 min after Pringle maneuver was opened. Formyl-methionyl-leucyl-phenlalanine(FMLP)-stimulated oxygen radical production was unchanged 15 min after Pringle maneuver was opened compared to baseline. Three hours after opening the Pringle maneuver, there was a decrease in FMLP-stimulated oxygen radical production by neutrophils (ns). Long-lasting effects of liver surgery demonstrated, at 48 and 120 h, FMLP-stimulated oxygen radical production exceeded baseline significantly.	A
Terpigorev et al. 2003	To study the morphology and functions of peripheral blood monocytes in vitro, their reactions to GC (glucocorticoid), and the correlation between cell sensitivity to GC and the results of glucocorticosteroid therapy in non-severe asthma patients.	42 (of 50) patients with persistent mild (n = 4) and moderate (n = 38) asthma (ages 16–69; 22 women 20 men). During the study, subjects stayed in the hospital under conditions free from contact with allergens, and received standard inhalation GC therapy in a daily dose of 1000 ug.	U	Initial parameters of baseline UPE in asthmatics and donors differed significantly (0.057+/−0.011 and 0.033+/−0.005, p<0.05). Baseline parameters of UPE were the same in patients with different efficiency of GC therapy, while after incubation of mononuclears with prednisolone in different concentration some differences between groups were revealed. UPE depression indexes revealed: the decrease of UPE parameters in group 2 (moderate GC responders) was more pronounced than in groups 1 (rapid GC responders) and 3 (non GC responders), which confirmed slight inhibitory effect of prednisolone on monocyte activity in vitro in group 2 patients. **	Signs of activation of circulating monocytes (hyper production of reactive oxygen forms) were observed in subjects with non-severe asthma. A significant correlation between the depression of monocyte activity by GC in vitro and the time of attaining clinical and functional remission during high-dose budesonide therapy was detected in steroid-sensitive subjects with non-severe asthma.	A
Tsai et al. 2004	To report that prophylactic high-dose L-arginine has a high capability of interacting with diabetic sera to generate harmful superoxide anions (O–2) as by-products which may subsequently propagate to form various types of other harmful free radicals.	10 (of 20) diabetic patients with a blood glucose level and HbA1c concentration higher than 200 mg/dl and 10%, respectively (age not specified).	U	When a fixed concentration of L-arginine was added to each of the diabetic sera, a higher amount of UPE (in counts/min) was generated, p<0.001. Conversely, L-arginine did not seem to elicit UPE when added to non-diabetic serum under similar conditions. ***	Data revealed the interaction between methylglyoxal glycation and L-arginine generated harmful O-2 as a by-product and subsequently could exacerbate the oxidative stress status of diabetic patients. For this reason, L-arginine should not be considered a preferable agent for blocking initial protein glycation by MG in diabetic patients.	A
Blood Plasma
Hans 1997	To investigate the effect of total intravenous anesthesia (TIVA) maintained with a continuous propofol (PPF) infusion on the plasma antioxidant capacity (PAOC) in neurosurgical patients.	18 (11 women 7 men, mean age of 53.2+/−22.5 years) patients scheduled to undergo the placement of a cerebrospinal shunt for nontraumatic hydrocephalus.	C	Plasma Antioxidant Capacity (assessed by UPE) increased significantly during anesthesia in all but 3 patients (p<0.001). Plasma's capacity to inhibit lipid peroxidation increased from 39.8+/−2.8% to 44.7+/−2.4%. No significant correlation was observed between increased resistance to lipid peroxidation and blood propofol concentrations (r = 0.07, NS). *	Continuous PPF infusion increased plasma antioxidant activity in patients during TIVA. Although no correlation was observed with blood PPF concentrations, this effect could be caused by PPF. Ultimately, there is no definitive proof yet.	A
Saliva
Goi 2007	To examine the response of oral peroxidase OPO reactivity to the Kraepelin test as a mental arithmetic stressor in smokers and non-smokers in addition to measuring: uric acid and IgA concentrations, flow rate, amylase activity as a salivary stress marker, thiocyanate level and UPE, which is indicative of salivary antioxidative and antibacterial abilities. The effect of smoking on the response of salivary peroxidase (SPO) and myeloperoxidase (MPO) activity to mental stress was also studied.	10 smokers (9 male 1 female) and 39 non-smokers (20 male 19 female) with mean ages 21.8+/−0.7 (range 21–23) and 21.3+/−1.1 (range 20–25).	U	Salivary UPE (measured by total number photons for 100 seconds after addition of H202) in the non-smoking group increased significantly just after the test, but changes in parameters were not significant (0 min before test  =  13.02+-6.53 counts/100 sec, 0 min after test = 16.62+-7.72 counts/100 sec). UPE levels were significantly higher in smokers, compared to non-smokers, following the test (non-smokers 0 min after test  =  16.62+/−7.72 counts/100 sec, smokers 0 min after test  =  11.40+/−3.98 counts/100 sec) ****	Results of the present study show defensive components are stronger in non-smokers than smokers. The IgA concentration, Amylase activity, and UPE were higher for non-smokers than smokers regardless of the Kraepelin test (the amount of UPE reflects the ability to consume H2O2 as an antioxidant and produces OSCN-, and reflects the strength of the innate immune system).	A

SIGN50: How well does the study address an appropriate and clearly focused question? U  =  Untreated control; P  =  Placebo; C  =  Crossover; UPE  =  Ultraweak photon emission; cps  =  counts per second; CL  =  chemiluminescence; A  =  Adequately covered; W  =  Well covered; P  =  Poorly addressed; * No substance was used to amplify the ROS to photon reaction; ** Luminol was used to amplify the ROS to photon reaction; *** Lucigenin was used to amplify the ROS to photon reaction; **** Hydrogen peroxide in presence/absence of iron sulfate was used to amplify the ROS to photon reaction; ***** UVA was used to amplify the ROS to photon reaction