The immunocompetence handicap hypothesis has attracted a lot of attention and an impressive amount of studies have been published on this topic (reviews in Owen-Ashley et al. 2004; Roberts et al. 2004; Muehlenbein & Bribiescas 2005). In a seminal paper, Folstad & Karter (1992) put forward a novel hypothesis to explain the honesty of testosterone-based sexual signals. Male zebra finches received subcutaneous implants filled with flutamide (an anti-androgen) or testosterone, or kept empty (control). The immunocompetence handicap hypothesis has been proposed as a possible mechanism ensuring honesty of SST on the basis that testosterone, in addition to its effect on sexual signals, also has an immunosuppressive effect. Whether it's dragging yourself out of bed, hitting a wall during workouts, or feeling that spark fade in the bedroom, declining testosterone levels are often the silent culprit. Because the normal growth of prostate tissue, as well as theprogression of certain intermediate and high-risk prostate cancers,are dependant on the presence of testosterone, it has been fearedthat improvement in testosterone status might increase the risk forthe development of benign prostatic hyperplasia or prostate cancer. Dietary supplementation withselenium increases intracellular thioredoxin reductase activity andincreases the efficiency of regeneration of ascorbic acid . The selenium-dependentthioredoxin reductases also catalyze the regeneration of ascorbicacid from oxidized dehydroascorbic acid (thereby contributing tointracellular antioxidation) 380,398. In addition to the absence of adverse reactionsduring these trials 361,362, the safety of exogenous α-lipoic acidwas demonstrated by the absence of adverse reactions during astudy in which men and women with metabolically stable diabetescomplicated by symptomatic diabetic sensorimotor polyneuropathyreceived intravenous injections of 600 mg of α-lipoic acid (5 injectionsper week for 3 weeks) . Among these subjects, the incidence ofgastrointestinal upset was increased slightly by 1200 mg and 1800mg of α-lipoic acid daily, although no other adverse reactions wereobserved. Dietary supplementation of rats exposed to these agents withα-lipoic acid has prevented or reversed these detrimental effects ontestosterone status 291,355,356,358,359. On the other hand, testosterone-dependent immunossuppression could also be the consequence of an ‘indirect pathway’ (Owen-Ashley et al. 2004) mediated by the pro-oxidant properties of this androgen, as firstly proposed by von Schantz et al. (1999). Androgens increase angiotensin II production, which regulates vasoconstriction by producing peroxides from NADH- and NADPH-oxidase (Reckelhoff 2001). Alternatively or additionally, the effect could be mediated by the role of androgens in the regulation of blood pressure. Α-Lipoic acid also stimulates increasedactivities of endogenous antioxidant enzymes, including SOD, catalase,GPx, and heme oxygenase-1 (HO-1) . In addition to reducing oxidizing compounds, α-lipoic acidcan recycle (reduce) other nonenzymatic antioxidants after theyhave become oxidized, prompting the descriptor, "antioxidant ofantioxidants" . During these reactions, α-lipoic acid becomes reduced todihydrolipoic acid, an intermediate that retains some antioxidantpotency before being either β-oxidized or S-methylated into excretorymetabolites 337,338. OR, odds ratio; CI, confidence interval; OBS, oxidative balance score. OR, odds ratio; CI, confidence interval; OBS, oxidative balance score; Q1, the lowest OBS group; Q2, the lower OBS group; Q3, the higher OBS group. OBS, oxidative balance score; Q1, the lowest OBS group; Q2, the lower OBS group; Q3, the higher OBS group. All analyses in this study were conducted using R (version 4.2.2), and a two-sided p-value of less than 0.05 was considered statistically significant. Finally, sensitivity analyses were also included in this study to ensure the robustness of the findings. The data in this study were available directly from the official NHANES website. Male zebra finches whose testosterone receptors were blocked by the anti-androgen (flutamide) showed the strongest resistance to free radicals and the strongest immune response, whereas T-implanted males had the weakest resistance to free radicals and the weakest immune response. T-cell mediated immune response for male zebra finches treated with anti-androgen (F; flutamide), control (C) or testosterone (T) implants during a 21-day period. Values are least square means±SE from an ANCOVA model including initial values of resistance to oxidative stress and body mass at sampling date as covariates. Changes in body mass and red blood cell resistance to free radicals during the course of the experiment were analysed by running ANCOVA models with final values as dependent variables and initial values as covariates. In addition, participants with missing data on PIR (497), educational background (1), energy intake (240), females (2,961), and sleep disorder (0) were also excluded. We hypothesize that there exists an inverse correlation between OBS and the risk of testosterone deficiency. Consequently, the potential association between overall oxidative-antioxidative status and low testosterone represents a promising area of investigation. A higher OBS indicates a stronger antioxidative capacity and it has emerged in recent years as a significant metric for assessing the balance between oxidative and antioxidative capacities within the body. Of particular importance is the recognition that environmental xenobiotics can exert testosterone-disrupting effects through oxidative mechanisms. In the adult male population of the United States, the prevalence of low testosterone is approximately 5.6%. The health concerns of males should not be overlooked or marginalized. The formazan absorbance was measured at 565 nmol l−1, and values represent the optical density per mg of protein. Untreated cells were utilized as controls for non-specific dye reduction. The yellow tetrazolium salt, MTT, is metabolized by mitochondrial succinic dehydrogenase activity of proliferating cells to yield a purple formazan reaction product.
