IODINE

Known for its role in thyroid health and association to wakame and other seaweeds. Well balanced levels of iodine are needed by the immune system. Marine sources also contain the so called molecular I2 form of iodine, as well as the “regular” type, and are often associated with lower cancer incidence in population studies in Japan, where for instance prostate cancer rates are only about 1/4 of those in western countries. Other metals from marine sources such as copper are negatively indicated in cancer development, so in dietary sources some moderation is indicated.

There is recent research on readily available molecular I2 iodine solution supplements in post surgery setting for breast cancers. Results confirmed promising pre-clinical results. Molecular iodine both exhibits direct suppression of cancer, and works effectively alongside first line chemotherapies to lengthen progression free periods and lower recurrence rates (see Examples). These study requires confirmation, but clearly show early potential for post-diagnostic use. Supporting this are similar improved outcomes using iodine solution forms in pre-emptive , preventative, surgery in high risk BRCA-1 carrying women. And, clinical trials in a third setting demonstrated that 5mg daily could notably increase innate immune response activity in breast cancer patients.

The proposed mechanism by which molecular iodine solutions support chemotherapy results involve regulation of the so called Th1/Th2 immune reponse. Iodine is shown boosting the tumor immune response by activating Th1 responses. But also damping the Th2 “allergy like” immune system activity, cancers use this upregulated “Th2”, to resist treatment actions of drugs. Its quite likely the same Th1/Th2 effects of iodine would help improve immunotherapy results. As well as breast cancer, many or even most cancers are linked to abnormal Th1/Th2 status. Including gynecologic and hematologic, gastric, head and neck, and prostate cancers.

Some , not all. studies show evidence that dietary iodine levels have preventative actions in breast, gastric, prostate and other cancers. Reseachers have proposed iodine deficiency in young women as a driver of rising rates of metastatic breast cancers, linked with low thyroid function. Iodine also works in synergy with selenium, and this may also affect how clearly studies are able to link these two compounds when investigated separately.  For prevention, dietary sources are recommended in studies, not supplements.

There are commercial product ambitions for preventing and treating non-cancerous benign prostatic hyperplasia (BPH), based on evidence from population studies lab work. In men with BPH, research shows 5 mg daily of Lugol’s solution improved major symptoms in a few months.

TYPICAL ABSORPTION LEVELS

High

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

MIXED
ANALYSIS

Highlighted Studies

We evaluated the effects of I2 [molecular iodine] during the initial and advanced stages of breast cancer with respect to toxicity, tumor response, survival at 5 years, and transcriptomic response. Our data indicate that supplementation with I2 improves the effectiveness of the treatment, decreasing side effects and increasing disease-free survival specially in advanced conditions (stage III). We also show that iodine supplementation induces tumor re-differentiation and ...

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A significant negative association was observed between blood iodine levels and breast cancer risk . Women with a blood iodine level greater than 38.0 µg/L had a significantly lower risk of breast cancer than women with blood iodine levels below 30 µg/L (quartile 4 vs. 1; HR = 0.49)….Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy [pre-emptive surgery] but require further validation and investigation of its eff...

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Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also pa...

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Among women with high selenium levels (above the median), high iodine levels were associated with a lower risk of breast cancer; the OR for above versus below the median was 0.75 (0.57–0.99). The corresponding OR for women with low selenium was 1.15 (0.87–1.50), and the Pinteraction was 0.06. Conclusions: The combination of high serum iodine levels and high selenium levels was associated with a lower risk of breast cancer.

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TABLE OF REFERENCES

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https://www.mdpi.com/2072-6643/11/7/16234This is a pilot study that analyzed the adjuvant effect of molecular iodine together with the most widely used chemotherapeutic treatment in Mexico against breast cancer. We evaluated the effects of I2 during the initial and advanced stages of breast cancer with respect to toxicity, tumor response, survival at 5 years, and transcriptomic response. Our data indicate that supplementation with I2 improves the effectiveness of the treatment, decreasing side effects and increasing disease-free survival specially in advanced conditions (stage III). We also show that iodine supplementation induces tumor re-differentiation and the reactivation of antitumor immune responses. This study establishes a framework for the proposal of a phase III study for the analysis of iodine supplementation in the treatment of advanced breast cancer.Our data corroborated those of previous reports showing the powerful antineoplastic effects of FEC/TE, as well as the induction of significant side effects [3,4]. One of the most interesting results obtained in the present study is the clear attenuation of severe side effects, such as diarrhea, neutropenia, and neuropathy, as well as the complete prevention of hand-foot syndrome and cardiotoxicity when I2 is supplemented during FEC/TE treatment. These results agree with those of our previous studies in rat and canine models, in which I2 supplementation mediated similar health benefits and cardioprotection [
https://www.mdpi.com/2072-6643/16/11/17883.5we measured blood iodine levels and observed a negative association with breast cancer risk, with a significantly lower risk observed in quartile 4 (iodine > 38.0 µg/L) compared with quartile 1 (iodine < 30 µg/L) (HR = 0.49; 95%CI: 0.27–0.87; p = 0.01). Conversely, a suggestive increase in ovarian cancer risk was observed at higher iodine levels (HR = 1.91; 95%CI: 0.64–5.67; p = 0.25). No significant association was found between iodine levels and overall cancer risk. Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy but require further validation and investigation of its effect on ovarian cancer risk and overall mortality. In our study, we observed a significant association between a relatively high blood iodine level and a reduced risk of breast cancer (quartile 4 vs. quartile 1; HR = 0.49; 95%CI: 0.27–0.87; p = 0.01). There was a suggestion of an increased risk of ovarian cancer associated with a high iodine level, but this was not statistically significant. Overall, the risk of all cancers combined was not associated with the serum iodine level.
https://www.mdpi.com/2218-273X/11/10/15013.5 Interestingly, I2 exerts antioxidant effects in the same way as ascorbic acid does, by producing electrons, and in ferric reactions that measure its capacity, I2 is 10 times more potent than ascorbic acid [14]. To the best of our knowledge there are currently no studies examining the role of I2 in the functionality of TETs. In conclusion, the preliminary findings from this study indicate that I2, when used in conjunction with conventional chemotherapy, induces immune activation and redirects the response to the Th1 pathway through methylation and demethylation mechanismsIn addition, I2 supplementation exerts effects on the immune system, acting as a direct genetic modifier [16] or as an attractor, increasing the amount of CD8+ lymphocytes within the tumor [17]. We previously demonstrated in a breast cancer pilot study that I2 supplementation exerted adjuvant effects when combined with conventional chemotherapy, reducing the residual tumor size, and increasing disease-free survival [17]. The RNA-seq analysis showed that I2-treated tumors exhibited significant activation of Th1, NK, and CD8 cytotoxicity pathways [17]. In the present study and using the same transcriptomic bank, we analyzed I2 and the chemotherapy treatment (Cht) in the immune scenario.
https://aacrjournals.org/cebp/article/29/7/1335/72349/Serum-Iodine-and-Breast-Cancer-Risk-A-Prospective3.5Among women with high selenium levels (above the median), high iodine levels were associated with a lower risk of breast cancer; the OR for above versus below the median was 0.75 (0.57–0.99). The corresponding OR for women with low selenium was 1.15 (0.87–1.50), and the Pinteraction was 0.06. Conclusions: The combination of high serum iodine levels and high selenium levels was associated with a lower risk of breast cancerThere is strong biological evidence of a potential protective effect from iodine regarding breast cancer. Iodine receptors, such as the sodium/iodide symporter (NIS), Pendrin, and the sodium/moncarboxylate transporter (SMCT), are present in breast tissue, which enables uptake of iodine (7). Iodine is necessary for normal breast development and iodine deficiency in rats causes breast atypia and dysplasia, which are reversible with iodine supplementation ... Iodine has also been proposed to act as an antioxidant to have antiproliferative effects
https://pmc.ncbi.nlm.nih.gov/articles/PMC5327366/3In conclusion, dietary iodine insufficiency represents a plausible explanation for the increasing incidence of breast cancer in young women with distant metastasis. In view of the established reduction in iodine levels in US women of childbearing age since the mid 70s, this group would be most vulnerable to increased breast cancer risk. The increased sensitivity of breast tissue to estradiol induced proliferative changes in the setting of dietary iodine insufficiency, provides a plausible mechanistic explanation for the increasing incidence of breast cancer with distant involvement in this age group. Based on the importance of iodine in thyroid and breast health, fetal brain development, as well as deficits in nutritional trends among younger women, iodine testing and management may be considered as a potentially important aspect for clinical practice.These findings provide a potential explanation for increased distant breast tumors at time of diagnosis. Since iodine deficiency is a major cause of hypothyroidism, breast cancer with distant metastasis may be promoted in part by reduced thyroid function, where slower tumor growth (precluding earlier diagnosis), yet increased invasiveness could be consequential. Iodine deficiency, therefore, may contribute to breast cancer and its progression directly within breast tissue, and secondarily by decreased thyroid function leading to metastasis. The importance of iodine in breast cancer is further emphasized by the adjuvant effects of iodine (I2) supplementation in combination with doxorubixin for breast cancer treatment
https://www.mdpi.com/2072-6643/16/7/10413After adjusting for confounding factors, higher seaweed consumption (>5 times/week) was significantly associated with lower TC prevalence (odds ratio [OR], 95% confidence interval [CI] = 0.42, 0.32–0.56, p-value < 0.001). In contrast, compared with moderate dairy consumption (3–4 times/week), lower dairy product intake (<1 time/week) was associated with higher TC prevalence (OR, 95% CI = 1.32, 1.05–1.67, p-value = 0.017). Our findings suggest that sufficient seaweed consumption may offer protection against TC, and incorporating dairy products into the diet may lower TC incidence in the Korean population. The most significant limitations of our study are the absence of 24 h urine samples for iodine status assessment and the lack of clinical data on the diagnosis of thyroid cancer.Our findings suggest that adequate seaweed consumption may offer protection against TC in the Korean population, and appropriate dairy product intake could be advantageous in reducing its incidence, potentially enhancing dietary habits for TC prevention in this population. In future research, collecting prospective data from large cohorts and conducting clinical studies that assess the influence of different iodine-rich foods on TC risk by measuring urinary iodine concentrations is imperative.
https://www.mdpi.com/1422-0067/25/16/88221I2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8+ cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol.According to our research, the I2 supplement alongside metronomic oCpp can improve its effectiveness and prevent potential inflammatory side effects. This combination can be considered a viable and cost-effective alternative to traditional hospital-based treatments, with potential for use in clinical protocols.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5437-31In immunosuppressed mice, the I2 supplement impairs implantation (incidence), tumoral growth, and proliferation of both types of cells. Xenografts of the animals treated with I2 decrease the expression of invasion markers like CD44, vimentin, urokinase plasminogen activator and its receptor, and vascular endothelial growth factor; and increase peroxisome proliferator-activated receptor gamma. Moreover, in mice with xenografts, the I2 supplement increases the circulating level of leukocytes and the number of intratumoral infiltrating lymphocytes, some of them activated as CD8+, suggesting the activation of antitumor immune responses.I2 decreases the invasive potential of a triple negative basal cancer cell line, and under in vivo conditions the oral supplement of this halogen activates the antitumor immune response, preventing progression of xenografts from laminal and basal mammary cancer cells. These effects allow us to propose iodine supplementation as a possible adjuvant in breast cancer therapy.
https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-12-451At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma.A robust body of evidence supports the notion that moderately high concentrations of molecular iodine exert apoptotic effects in several cancer cells as well as general antioxidant actions in the organism. In the present work we demonstrated that, through activation of PPARγ, long-term I2 treatment increases the tumor sensitivity to DOX, inhibits chemoresistance, and exerts cardioprotective effects, allowing a four-fold reduction in the therapeutic dose of DOX. These results, together with the adjuvant neoplastic effects of I2, lead us to propose Doxorubicin in combination with I2 supplement as a promising strategy against breast cancer progression.

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