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Male sex hormones, predominantly testosterone, have been identified as significant modulators of immune function. Studies further uncovering immune-specific effects of androgens are needed and may lead to the identifi-cation of pathways that could be targeted therapeutically to inhibit the incidence and progression of autoimmunity and cancer. Thus, testosterone may be predictive of increased cancer risk, warranting further research into the immunosuppressive and potential cancer-promoting effects of testosterone during early establishment of cancer. In a separate study of induced thyroid cancer in male mice, gonadectomy led to an upregulation of tumor-suppressor genes (264). More direct evidence supporting a tumorigenic role for androgen in cancer development comes from animal studies, where susceptibility to cancer in response to chemicals and genetic manipulation often depend on sex hormone levels (261). Cancer is known to induce a stage of chronic inflammation, and thus in order to study a potential causal relationship between testosterone and cancer development, retrospective cohort analyses investigating levels of testosterone prior to the diagnosis of cancer are necessary.
Note that because ultraviolet rays can cause skin cancer, it is important to avoid excessive sun exposure and in general, tanning beds should not be used. Certain mushrooms contain some vitamin D2; in addition some commercially sold mushrooms contain higher amounts of D2 due to intentionally being exposed to high amounts of ultraviolet light. The doses in these supplements are widely available and generally well-tolerated. And when it comes to limiting risk of COVID-19, it is important to practice careful social distancing and hand washing. Even if vitamin D has some benefit, don’t skip your flu shot. More research is needed before we can definitively say that vitamin D protects against the flu and other acute respiratory infections.
In one yearlong study, 65 men who took 3,300 IU of vitamin D daily increased their testosterone levels by 20% over those who didn't. A prospective study among healthy young adults in the US found that White individuals with the highest levels of serum vitamin D had a 44% lower risk of developing T1D in adulthood than those with the lowest levels. Notably, among the participants who had the lowest blood levels of vitamin D at the beginning of the study, vitamin D supplementation did reduce risk of diabetes. The authors noted that a lack of effect of vitamin D may have been due to the majority of participants having vitamin D blood levels in a normal range of greater than 20 ng/mL, which is considered an acceptable level to reduce health risks.
Create healthy, balanced meals using this visual guide as a blueprint. Use healthy oils (like olive and canola oil) for cooking, on salad, and at the table. Catching the sun’s rays in a sunny office or driving in a car unfortunately won’t help to obtain vitamin D as window glass completely blocks UVB ultraviolet light. The low amounts of the vitamin found in food are unlikely to reach a toxic level, and a high amount of sun exposure does not lead to toxicity because excess heat on the skin prevents D3 from forming. Vitamin D toxicity most often occurs from taking supplements. People who cannot tolerate or do not eat milk, eggs, and fish, such as those with a lactose intolerance or who follow a vegan diet, are at higher risk for a deficiency. If one is not eating enough vitamin D and does not receive enough ultraviolet sun exposure over an extended period (see section above), a deficiency may arise.
A more direct test of immuno-modulation would involve manipulation of testosterone levels, though such an experimental design would have reduced ecological validity. Additionally, developmental changes at early ages may have led to differences between individuals in both testosterone and immune function, leading to associations that are not necessarily causal, but rather correlates of other phenotypic variables. Androgen receptors are present on T-cells (Benten et al. 1999), but their numbers might be dynamically regulated in response to baseline androgen levels and other feedback mechanisms. Previous studies report positive associations between androgens and anti-inflammatory cytokines (Liva and Voskuhl 2001; Malkin et al. 2004).
Androgen-mediated suppression of immune reactivity and inflammation increases the threshold for autoimmunity to develop, but likely lowers the threshold for cancer. With tumor-suppressor proteins present, CCL5 chemokine expression by tumor cells increased driving infiltration by inflammatory macrophages and CD8+ cytotoxic T cells and subsequently reduced tumor growth. Many factors have been proposed to explain this discrepancy including environmental exposures (smoking, obesity, infections) and sex hormone levels and signaling (255, 258). Immune cells must be capable of distinguishing modified-self from self, and yet, must not become unduly activated against unmodified self-antigens. Overall, at least in mice, it seems as though lupus pathogenesis may proceed in fundamentally different ways in male and female mice. More current studies evaluating a relationship between androgens and complement has to our knowledge not been performed.