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Pharmacology, Toxicology and Pharmaceutical Science » Pharmacology » "Pharmacology and Nutritional Intervention in the Treatment of Disease", book edited by Faik Atroshi, ISBN 978-953-51-1383-6, Published: May 28, 2014 under CC BY 3.0 license. © The Author(s).

Chapter 9

Impact of CoQ10, L-Carnitine and Cocktail Antioxidants on Oxidative Stress Markers in HIV Patients — Mini Review and Clinical Trial

By M Sauka, G Selga, A Skesters, A Silova, T Westermarck, A Latvus and F Atroshi
DOI: 10.5772/58415

Article top


Catalase level of HIV infected individuals and healthy subjects (k/g Hb)Catalase level of
Figure 1. Catalase level of HIV infected individuals and healthy subjects (k/g Hb)Catalase level of
Vitamin E level of HIV infected individuals and healthy subjects (μg /ml)
Figure 2. Vitamin E level of HIV infected individuals and healthy subjects (μg /ml)
Selenium level of HIV infected individuals and healthy subjects (μ/g Hb)
Figure 3. Selenium level of HIV infected individuals and healthy subjects (μ/g Hb)

Impact of CoQ10, L-Carnitine and Cocktail Antioxidants on Oxidative Stress Markers in HIV Patients — Mini Review and Clinical Trial

M Sauka1, G Selga1, A Skesters1, A Silova1, T Westermarck2, A Latvus3 and F Atroshi4

1. Introduction

Nutritional deficiencies have long been recognized as an important problem among HIV-1-seropositive individuals. They have a great demand for nutrients because of the stress placed on their immune systems. Moreover, poor nutrition may also affect drug effectiveness or increased toxicity [34-37]. It has been shown that micronutrient deficiencies are associated with more rapid HIV-disease progression and higher HIV-1 related mortality [38-40]. Supplementation of micronutrient has delayed time to AIDS and improved survival, suggesting that supplementation could offer a simple and relatively inexpensive strategy to slow HIV-1 progression [41, 42].

HIV infected patients present changes in components of the antioxidant defense system, which may be the result of excessive production of oxygen-derived species during the development of the disease (Pace and Leaf, 1995) and that cells infected with HIV can enhance production of O2•− [43]. This phenomenon combined with a deficiency in key antioxidant enzymes superoxide dismutase and catalase, and a decreased concentrations of the antioxidant vitamins [44] may lead to severe oxidative stress in HIV-infected patients. Humans infected with human immunodeficiency virus (HIV) have been shown to be under chronic oxidative stress [44-46], which is the result of imbalance between free radical (or pro-oxidant) production and antioxidant action. In HIV infection, oxidative stress may be caused by both overproduction of reactive oxygen species (ROS) and a simultaneous deficiency of antioxidant defenses [47, 48]. Oxidative stress induced by ROS play a critical role in the stimulation of HIV replication and the development of immunodeficiency [49, 50].


Figure 1.

Catalase level of HIV infected individuals and healthy subjects (k/g Hb)Catalase level of


Figure 2.

Vitamin E level of HIV infected individuals and healthy subjects (μg /ml)

Many studies have focused on the role of nutritional supplements to attenuate signs and symptoms of HIV. Of these, some have reported favorable results, while many others have reported no benefit of the selected nutrient. Despite these mixed findings, recommendations for the use of nutritional supplements for the purposes of attenuating HIV are rampant. Based on this background, we have assessed the antioxidant status among HIV-infected patients on oxidative stress after antioxidant supplementation.

2. Subjects and methods

2.1. Subjects

Open clinical trial study was implemented to access antioxidant status among HIV-infected male volunteers in Latvia. Twenty six HIV-positive males (age 35.3 ± 2.5) whose serostatus are known were studied. They were recruited among two non-governmental HIV infected patients’ support organizations by “snow-ball” methodology using gatekeepers as contact persons. All participants in the research study were volunteers and their agreement to participate was get through their gatekeepers. The HIV-infected subjects represented a broad range of disease progression. None of the screened subjects had (CD4) T cell counts less than 200x109/L.

Exclusion criteria for the study groups were as follows: they were over 18 years old, have not used antioxidants as food supplement two months before the study, had no active opportunistic infections or malignancies, had readily mobile, and were no drug users. Any information of partner identifications was not used in the written information

For the control group 10 uninfected males were selected among uninfected friends and relatives of HIV-infected individuals. Control subjects had no acute or chronic illness and were not taking any medications or nutritional supplements.

HIV-infected individuals used food supplements– antioxidant cocktail for 6 month, including 250 mg L-carnitine (Bio-CarnitineTM), 800 μg vitamin A, 15 mg vitamin E, 90 mg vitamin C, 2 mg vitamin B6, 15 mg Zn, 100 mg CoQ10 and 75 μg selenium (organic) (Bio-SeleniumTM+Zn) a day. All subjects underwent an initial screening and after 6 months that included an anthropometric (weight and height) and biochemical (complete blood count, bilirubin, albumin, from liver panel-alanine aminotranferase (ALT) and alkaline aminotranferase (), from lipid profile total holesterol and triglicerides. All patients were evaluated with regard to the blood antioxidant system, specifically superoxide dismutase (SOD), catalase (CAT) selenium-dependent glutathione peroxidase (GSH-Px, trace element selenium, and α-tocopherol).

Participants will be involved in the study only after obtaining informed consent. The study protocol was approved by the ethics committee of the Latvian Institute of Cardiology for Clinical and Physiological Research, Drug and Pharmaceutics Product Clinical Investigation.

2.2. Laboratory analysis

After overnight fasting, venous blood samples were collected from all study subjects. Biochemical determinations were done at the hospital laboratory. CD4+and CD8+cell count was estimated by FACSscan flowcytometry (BD Becton Dickimon). Alanine aminotranferase (ALT) and alkaline aminotranferase were estimated by kinetic reaction (Hitachi 917, Roche Diagnostics), bilirubin, albumin and total protein by two point colour reaction (Hitachi 917, Roche Diagnostics). From lipid profile total holesterol and triglycerides were estimated by using fermentative colour reaction (Hitachi 917, Roche Diagnostics). Blood antioxidant system was evaluated at Riga Stradinš University laboratory. Selenium and α-Tocophrol concentrations in plasma were measured using fluorometric method. Other measurements were also included such as catalase and GSHPX.

2.3. Statistical analyses

Using the SPSS 14.0 for Windows software standard version, statistical analyses were performed. All group data are expressed as means ± SEMs. The HIV-positive group was compared with the seronegative control subjects by using one way ANOVA. The minimal level of significance was identified at P < 0.05. All patients were evaluated with regard to the blood antioxidant system, specifically superoxide dismutase (SOD) and glutathione peroxidase.

3. Results

Subject characteristics, including CD4+cell count, CD8+cell count, and CD4/CD8 ratio, weight, body mass index (BMI, in kg/m2), are shown in Table 1. At initial screening HIV-infected subjects were significantly lower weight and BMI compared to healthy subjects. There were insignificant changes between initial screening and after 6 months. The range of CD4+cell counts was broad, from 282 to 1830 x 106 cells/L at the initial screening and from 323 to 1687 after 6 months CD4/CD6 ratio was from 0.1 to 1.7 at the initial screening and from 0.1 to 3.4 after 6 months of using food supplements, CD8+cell counts was from 272 to 4525 at the initial screening and from 222 to 4851 after 6 months.

Baseline After 6 months
n Mean±SE n Mean±SE
Weight HIV-infected 2673.1±2.11374.7±2.8
healthy uninfected 1082.4±2.6983.3±2.7
BMIHIV-infected 2622.5±0.61323.0±0.8
CD4+HIV-infected 25698.4±74.321743.6±87.4
CD8+HIV-infected 251641.9±188.1211341.0±216.1
CD4+/CD8HIV-infected 250.6±0.1210.9±0.2

Table 1.

Effect of antioxidant supplementation on body weight, body mass index and immune function in HIV patients.

Antioxidant status is shown in Table 2. At the baseline HIV-positive patients had significantly lower GSHPX and CAT concentrations compare to healthy subjects (p<0.05), but did not differ after 6 months using food supplements. There were insignificant differences in SOD and MDA measurements and α-Tocopherol concentration at the initial screening, but differed significantly after 6 months compare to HIV-infected and healthy individuals. Changes of biochemical measurements (alanine aminotranferase, alkaline aminotranferase, bilirubin, albumin and total protein, total holesterol and triglicerides) were not significant between groups of HIV-infected and healthy individuals as well as at the initial screening and after 6 months after use of food supplements. Additionally, two HIV-infected individuals from 26 involved in the study reported that after the use of antioxidant cocktail, gingival bleeding was stopped. One reported this symptom for two years before the study and one reports half a year this problem before study.

Measuremetns groups Baseline After 6 months

Table 2.

Effect of antioxidants supplementation on antioxidant enzymes, selenium, vitamin E and lipid peroxidation in HIV patients.

4. Discussion

There has been increasing interest in the application of antioxidants to many diseases as information is constantly gathered linking the development of HIV to oxidative stress [51]. Antioxidants are believed to function interactively and synergistically to neutralize reactive oxygen species (ROS). Reactive oxygen species include molecules like hydrogen peroxide; ions like the hypochlorite ion; radicals like the hydroxyl radical; and the superoxide anion, which are an ion and a radical.

All subjects from the current study are at low serum selenium level (which is about 80 – 120 μg /L in Europe), and stayed as that even after use of antioxidants supplements, including selenium. Similar trend was also notice in the selenoenzyme glutathione peroxidase (GSHPx) level among HIV patients. Low serum selenium was defined as a serum level ≤ 85 µg/l [52]. Selenium deficiency, more than any other nutrient, has been documented to correlate with progression and mortality of HIV [53]. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS [54]. When taken as a supplement, selenium modulates the cellular response to oxidative stress, inducing a faster restoration of the endogenous antioxidative defence system against the production of reactive oxygen species [55]. Glutathion peroxidase controls the interacellular level of hydrogen peroxide, reducing the formation of reactive oxygen species that can induce lipid peroxidations with consequent damage to the cellular membranes [56].


Figure 3.

Selenium level of HIV infected individuals and healthy subjects (μ/g Hb)

The loss of CD4 T lymphocytes is a central factor in the progression of HIV infection to AIDS. The key role of these cells in regulating and amplifying the immune response means that any decline in their number results in deficits in both humoral and cell-mediated immunity [57]. Both the CD4 percentage and the CD4:CD8 ratio are also affected by changes in the number of CD8 cells, which tends to rise through the course of HIV infection [58].This study demonstrates that after supplementation, there is an increase in CD4 T cells in HIV patients. Several research studies have indicated that the apoptosis of CD4 cells contributing to HIV progression does not result solely from HIV infection, but largely from antioxidant imbalances in the host [43, 59, 60]. Activation of latent HIV state can be stimulated in the presence of reactive oxygen species (ROS) through the stimulation of oxygen-responsive transcription factors, specifically NF-kB, which induces HIV replication in the infected T-lymphocyte.

The mean serum malondialdehyde (MDA) concentrations in this study were significantly elevated in HIV infected patients. Serum concentration of total serum antioxidant status (TAS) was increased after supplementation. Our data indicate that severe oxidative stress occurs in the serum of HIV patients in comparison with controls ones and the inclusion of antioxidants in the therapeutic approach in managing HIV patients may prevent the additional free radicals damage. It has been shown that cells infected with the HIV undergo a significant amplification of O2 generation. This phenomenon combined with a deficiency in key antioxidant enzymes (SOD and CAT) and a decreased concentration of the antioxidant vitamins, may lead to severe oxidative stress in HIV-infected patients. Consequently these conditions may in turn be responsible for the DNA base modifications observed in this study [43]. Serum MDA adducts also tended to correlate inversely with expression of CD127 on T cells was shown [61]. Study in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls [62] showed that placental mitochondria malondialdehyde (MDA) concentrations and mtDNA content in placenta and cord blood were similar between groups. Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients [44]. Furthermore, as an antioxidant, vitamin E [63]and atherosclerotic lesions contain oxidized lipids [64], therefore, supplementation with vitamin E would decrease heart disease risk. It has been reported that α-tocopherol concentrations in serum are regulated by the α-tocopherol transfer protein and are dependent on serum lipid concentrations because α-tocopherol is non-specifically transported by lipoproteins [63]. Serum micronutrient concentrations along with surrogate markers of atherosclerosis in a cohort of HIV infected adults were studied [65](Falcone et al. 2010), the highest tertile of serum vitamin E concentration was associated with higher common and internal carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores [65]. The authors concluded that elevated serum vitamin E values may increase the risk of cardiovascular complications in HIV-infected adults [65].

There appears to be a possible role for antioxidants supplements. However, these supplements cannot effectively eliminate HIV signs and symptoms and the optimal dosage of these nutrients is (whether used alone or in combination) has to defined


1 - WHO. HIV/AIDS.Global situation and trends, 2013.
2 - Sicotte M, Langlois EV, Aho J, Ziegler D, Zunzunegui MV. Association between nutritional status and the immune response in HIV + patients under HAART: protocol for a systematic review. Syst Rev. 2014 Feb 10;3(1):9. [Epub ahead of print]
3 - Kaio DJ, Rondó PH, Souza JM, Firmino AV, Luzia LA, Segurado AA. Vitamin A and Beta-Carotene Concentrations in Adults with HIV/AIDS on Highly Active Antiretroviral Therapy. J Nutr Sci Vitaminol (Tokyo). 2013;59(6):496-502.
4 - Fawzi, W. Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children. Clin. Infect. Dis., 2003, 37 Suppl 2, S 112 – 6.
5 - Nkengfack GN, Torimiro JN, Englert H. Effects of antioxidants on CD4 and viral load in HIV-infected women in sub-Saharan Africa - dietary supplements vs. local diet. nt J Vitam Nutr Res. 2012 Feb;82(1):63-72.
6 - van Lettow M, Harries AD, Kumwenda JJ, Zijlstra EE, Clark TD, Taha TE, Semba RD. Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with pulmonary tuberculosis with and without HIV co-infection in Malawi. BMC Infect Dis 2004;4:61.
7 - Stone CA, Kawai K, Kupka R, Fawzi WW. Role of selenium in HIV infection. Nutr Rev 2010; 68:671–81.
8 - Campa A, Baum MK. Micronutrients and HIV infection. HIV Ther 2010;4:437–69.
9 - Rayman MP. Selenium and human health. Lancet 2012;379:1256–68.
10 - Odeh M. The role of zinc in acquired immunodeficiency syndrome. J Intern Med. 1992 May;231(5):463-9.
11 - Baum MK, Shor-Posner G, Lu Y, Rosner B, Sauberlich HE, Fletcher MA, Szapocznik J, Eisdorfer C, Buring JE, Hennekens CH. Micronutrients and HIV-1 disease progression. AIDS. 1995 Sep;9(9):1051-6.
12 - Graham NM, Sorensen D, Odaka N, Brookmeyer R, Chan D, Willett WC, Morris JS, Saah AJ. Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr. 1991;4(10):976-80.
13 - Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol. 1996 Jun 15;143(12):1244-56.
14 - Miyamoto H, Araya Y, Ito M, Isobe H, Dosaka H, Shimizu T, Kishi F, Yamamoto I, Honma H, Kawakami Y. Serum selenium and vitamin E concentrations in families of lung cancer patients. Cancer. 1987 Sep 1;60(5):1159-62.
15 - Delmas-Beauvieux MC, Peuchant E, Couchouron A, Constans J, Sergeant C, Simonoff M, Pellegrin JL, Leng B, Conri C, Clerc M. The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene. Am J Clin Nutr. 1996 Jul;64(1):101-7. Erratum in: Am J Clin Nutr 1996 Dec;64(6):971.
16 - Flax VL, Bentley ME, Combs GF Jr, Chasela CS, Kayira D, Tegha G, Kamwendo D, Daza EJ, Fokar A, Kourtis AP, Jamieson DJ, van der Horst CM, Adair LS. Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study. Am J Clin Nutr. 2014 Feb 5. [Epub ahead of print].
17 - Mburu S, Marnewick JL, Abayomi A, Ipp H. Modulation of LPS-induced CD4+ T-cell activation and apoptosis by antioxidants in untreated asymptomatic HIV infected participants: an in vitro study. Clin Dev Immunol. 2013;2013:631063. doi: 10.1155/2013/631063. Epub 2013 Nov 21.
18 - Hillesheim E, Lima LR, Silva RC, Trindade EB. Dietary intake and nutritional status of HIV-1-infected children and adolescents in Florianopolis, Brazil. Int J STD AIDS. 2013 Dec 18. [Epub ahead of print].
19 - Kaiser JD, Campa AM, Ondercin JP, Leoung GS, Pless RF, Baum MK. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):523-8
20 - Baeten JM, McClelland RS, Richardson BA, Bankson DD, Lavreys L, Wener MH, Overbaugh J, Mandaliya K, Ndinya-Achola JO, Bwayo JJ, Kreiss JK. Vitamin A deficiency and the acute phase response among HIV-1-infected and -uninfected women in Kenya. J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):243-9.
21 - Guo Y, Pino-Lagos K, Ahonen CA, Bennett KA, Wang J, Napoli JL, Blomhoff R, Sockanathan S, Chandraratna RA, Dmitrovsky E, Turk MJ, Noelle RJ. A retinoic acid--rich tumor microenvironment provides clonal survival cues for tumor-specific CD8(+) T cells. Cancer Res. 2012 Oct 15;72(20):5230-9.
22 - Irlam JH, Visser MM, Rollins NN, Siegfried N. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD003650. doi: 10.1002/14651858.CD003650.
23 - Thorne-Lyman AL, Fawzi WW. Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2012 Jul;26 Suppl 1:36-54. doi: 10.1111/j.1365-3016.2012.01284.
24 - Forrester JE, Wang XD, Knox TA, Borek CG, Tang AM, Johnson EJ. Factors associated with serum retinol, alpha-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chronic hepatitis C, and drug use. J Public Health Policy. 2009 Sep;30(3):285-99.
25 - Monteiro JP, Freimanis-Hance L, Faria LB, Mussi-Pinhata MM, Korelitz J, Vannucchi H, Queiroz W, Succi RC, Hazra R. Both human immunodeficiency virus-infected and human immunodeficiency virus-exposed, uninfected children living in Brazil, Argentina, and Mexico have similar rates of low concentrations of retinol, beta-carotene, and vitamin E. Nutr Res. 2009 Oct;29(10):716-22.
26 - Villamor E, Koulinska IN, Aboud S, Murrin C, Bosch RJ, Manji KP, Fawzi WW. Effect of vitamin supplements on HIV shedding in breast milk. Am J Clin Nutr. 2010 Oct;92(4):881-6.
27 - Dror DK, Allen LH. Vitamin E deficiency in developing countries. Food Nutr Bull. 2011 Jun;32(2):124-43.
28 - Isanaka S, Mugusi F, Fawzi WW. Standard-dose vs high-dose multivitamin supplements for HIV--reply. JAMA. 2013 Feb 13;309(6):546. doi: 10.1001/jama.2012.216995.
29 - Sudfeld CR, Isanaka S, Mugusi FM, Aboud S, Wang M, Chalamilla GE, Giovannucci EL, Fawzi WW. Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort. Am J Clin Nutr. 2013 Jun;97(6):1278-87.
30 - Abrams B, Duncan D, Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J Acquir Immune Defic Syndr. 1993 Aug;6(8):949-58.
31 - Folkers K, Langsjoen P, Nara Y, Muratsu K, Komorowski J, Richardson PC, Smith TH. Biochemical deficiencies of coenzyme Q10 in HIV-infection and exploratory treatment. Biochem Biophys Res Commun. 1988 Jun 16;153(2):888-96.
32 - Cherry CL, Mobarok M, Wesselingh SL, Fain R, Weinstock S, Tachedjian G, Srivastava S, Tyssen DP, Glass JD, Hooker DJ. Ubisol-Aqua: coenzyme Q10 prevents antiretroviral toxic neuropathy in an in vitro model. Curr HIV Res. 2010 Apr;8(3):232-9.
33 - Xue SY, Hebert VY, Hayes DM, Robinson CN, Glover M, Dugas TR. Nucleoside reverse transcriptase inhibitors induce a mitophagy-associated endothelial cytotoxicity that is reversed by coenzyme Q10 cotreatment. Toxicol Sci. 2013 Aug;134(2):323-34.
34 - Hickey, M. S. Nutritional support of patients with AIDS. Surg.Clin.North Am. 71:645-664, June 1991.
35 - Karter DL, Karter AJ, Yarrish R, Patterson C, Kass PH, Nord J, Kislak JW. Vitamin A deficiency in non-vitamin-supplemented patients with AIDS: a cross-sectional study. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):199-203.
36 - Timbo BB, Tollefson L. Nutrition: a cofactor in HIV disease. J Am Diet Assoc. 1994 Sep;94(9):1018-22.
37 - Augustus LJ. Nutritional care for patients with HIV. Am J Nurs. 1997 Oct;97(10):62-5.
38 - Beach RS, Mantero-Atienza E, Shor-Posner G, Javier JJ, Szapocznik J, Morgan R, Sauberlich HE, Cornwell PE, Eisdorfer C, Baum MK: Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 1992, 6:701-708.
39 - Semba RD, Graham NM, Caiaffa WT, Margolick JB, Clement L, Vlahov D: Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med 1993, 153:2149-2154.
40 - Tang AM, Graham NM, Semba RD, Saah AJ: Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS 1997, 11:613-620.
41 - Jiamton S, Pepin J, Suttent R, Filteau S, Mahakkanukrauh B, Hanshaoworakul W, Chaisilwattana P, Suthipinittharm P, Shetty P, Jaffar S: A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003, 17:2461-2469.
42 - Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ: A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004, 351:23-32.
43 - Kameoka M, Kimura T, Ikuta K. Superoxide enhances the spread of HIV-1 infection by cell-to-cell transmission. FEBS Lett. 1993 Sep 27;331(1-2):182-6.
44 - Jaruga P, Jaruga B, Gackowski D, Olczak A, Halota W, Pawlowska M, Olinski R. Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients. Free Radic Biol Med. 2002, 32(5):414-20.
45 - Peterhans E. Oxidants and antioxidants in viral diseases: disease mechanisms and metabolic regulation.J Nutr. 1997 May;127(5 Suppl):962S-965S.
46 - Pace GW, Leaf CD. The role of oxidative stress in HIV disease. Free Radic Biol Med. 1995 Oct;19(4):523-8.
47 - Smit E, Tang A. Nutritional assessment in intravenous drug users with HIV/AIDS. J Acquir Immune Defic Syndr. 2000 Oct 1;25 Suppl 1:S62-9.
48 - Tang AM, Smit E, Semba RD, Shah N, Lyles CM, Li D, Vlahov D. Improved antioxidant status among HIV-infected injecting drug users on potent antiretroviral therapy.J Acquir Immune Defic Syndr. 2000 Apr 1;23(4):321-6.
49 - Wong GHW, McHugh T, Weber R, Goeddel DV. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus infected cells to heat and radiation. Proc Natl Acad Sci U S A 1991;88:4372–6.
50 - Kotler DP. Nutritional management of patients with AIDS-related anorexia. Semin Gastrointest Dis. 1998 Oct;9(4):189-99.
51 - Kupka R, Msamanga GI, Spiegelman D, Morris S, Mugusi F, Hunter DJ, Fawzi WW: Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania. J Nutr 2004, 134:2556-2560.
52 - Hardy G, Hardy I. Selenium: the Se-XY nutraceutical. Nutrition. 2004 Jun;20(6):590-3.
53 - Baum MK, Shor-Posner G, Lai S, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997;15:370–4.
54 - Rayman M.P. (2000).The importance of selenium to human health. Lancet. 15;356(9225):233-41.
55 - Jozanov-Stankov O, Demajo M, Djujić I, Mandić M. Selenium intake as a modulator of responsiveness to oxidative stress. J Environ Pathol Toxicol Oncol. 1998;17(3-4):251-7.
56 - Levander OA, Beck MA. Selenium and viral virulence. Br Med Bull. 1999;55(3):528-33.
57 - Grossman Z, Meier-Schellersheim M, Sousa AE, Victorino RM, Paul WE. CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause? Nat Med 2002; 8:319–323.
58 - Highleyman, L. (2003). Monitoring tests for people with HIV. Bulletin of Experimental Treatments for AIDS: Retrieved July 2003 from Hogg, R. et. al. (2001). Rates of disease progression based on CD4 cell count and viral load after initiating drug therapy. Journal of the American Medical Association, 286(20). 2568-2577.
59 - Sandstrom PA, Murray J, Folks TM, Diamond AM. Antioxidant defenses influence HIV-1 replication and associated cytopathic effects. Free Radic Biol Med 1998;24:1485-1491.
60 - Droge W, Eck HP, Gmunder H, Mihm S. Requirement for prooxidant and antioxidant states in T cell mediated immune responses. Relevance for the pathogenic mechanisms of AIDS? Klin Wochenschr 1991;69:118-122.
61 - Kalinowska M, Bazdar DA, Lederman MM, Funderburg N, Sieg SF. Decreased IL-7 responsiveness is related to oxidative stress in HIV disease. PLoS One. 2013;8(3):e58764. doi: 10.1371/journal.pone.0058764. Epub 2013 Mar 7.
62 - Ross AC, Leong T, Avery A, Castillo-Duran M, Bonilla H, Lebrecht D, Walker UA, Storer N, Labbato D, Khaitan A, Tomanova-Soltys I, McComsey GA. Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress. HIV Med. 2012 Feb;13(2):98-106.
63 - Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr 2007;27:347–62.
64 - Diaz MN, Frei B, Vita JA, Keaney JFJ. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408–16.
65 - Falcone EL, Mangili A, Tang AM, et al. Micronutrient concentrations and subclinical atherosclerosis in adults with HIV. Am J Clin Nutr , 2010;91:1213–9