ZINC

A recent clincial trial compared immunotherapy response in lung and digestive tract cancers to patients levels of zinc. Not only was zinc identifed as an independent indicator of likely positive response to therapy, but also a major factor in reducing progression risks. This is similar results with sodium though with a lower impact level. More data like this is emerging for magnesium.

Zinc deficiency has a role in cancer formation and progression, most studied in prostate cancers but also seen in tissue samples of kidney, liver, ovarian, cervical, pancreas. esophageal cancers. Very recent meta-analysis into breast cancer survival over 10 years showed that higher pre-diagnosis levels were associated with better outcomes, whilst higher copper levels reduced survival (see Concerns). The research discusses low dose zinc supplementation, while other researcher suggest active treatment with copper chelation . Curcumin is known as a natural copper chelator [absorber].

Similar research has shown increased survival benefits for relatively higher selenium-zinc combined levels – including liver, lung, kidney and throat cancer. And in immunotherapy responses, up to 50% of tumors show low expression of so called CDKN2A activity resulting in high metabolic demand for zinc in the tumor microenvironment. This weakens natural immune response to cancer. In pre-clinical study, zinc supplementation was able to reverse this.

Zinc contributes to healthy cell proliferation, differentiation, and mortality (via apoptosis). Zinc levels have been shown in meta-analysis to play a clear and significant role in moderation of insulin resistance and systemic inflammation levels (see References), both of which are linked to faster cancer progression rates. Its important to raise levels before and during treatment based on the clinical observations in outcomes.

Clinical trials during therapy remain few in number. A recent 2023 publication in US does show benefits for prostate cancer risks for progression with a strong association to low dose zinc 1- 24 mg daily (see references). However, this was indicated for patients who took these supplements both before and after diagnosis, whilst significant effects were not reported for use only during a treatment phase.

Doses >75 or 100mg daily is reported as a risk factor for breast and prostate cancer including metastasis. The consensus then, is that low dose zinc 15 to 20 mg or so and in conjunction with low dose dietary selenium, shows clear advantages in both prevention and slowing of disease for some cancers. Levels that can come from dietary sources in the first instance. Where dietary source may be lacking, supplements are a complementary solution, if following a largely vegan/ vegetarian regime for instance.

TYPICAL ABSORPTION LEVELS

High

EXAMPLES OF IMPROVED OUTCOMES

YES

PRE-DIAGNOSIS OR PREVENTION

YES

Highlighted Studies

Our study provides preliminary evidence that there is a correlation between serum zinc levels and the efficacy of immunotherapy. This correlation is reflected in treatment response and overall survival in patients with advanced cancer. These findings not only underscore the importance of zinc in immune regulation and cancer therapy but also pave the way for developing predictive biomarkers and synergistic treatment strategies to enhance immunotherapy outcomes….These findings highlight t...

The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio. The multivariate hazard ratio (HR) for breast cancer mortality was 2.07 [high copper is a clear risk factor] for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific su...

Among the total number of 338 prostate cancer patients, there were 77 (22.8%) patients with corresponding extreme quartiles of Se and Zn, whereas 49 (14.5%) patients had corresponding first quartiles of Se and Zn [i.highest relative amounts] and 28 (8.28%) patients had corresponding fourth quartiles [lowest] of Se and Zn . In the multivariable model, our findings show that individuals who were in both the lowest Se quartile and the lowest Zn quartile had almost a 21-fold lower chance of 5-yea...

For patients in the highest quartile [those with highest levels] of blood zinc/selenium ratio, compared to those in the lowest, the HR [Hazard Ratio] was 2.53. Our study suggests that selenium levels, combined selenium and zinc levels. and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients……..additional studies have shown that zinc deficiency in patients with breast, gastric, colorectal, lung and pr...

TABLE OF REFERENCES

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https://tspace.library.utoronto.ca/bitstream/1807/138235/1/nutrients-16-01000.pdf	3.5	In the present study, we observed that a low serum zinc level (≤762.7 µg/L) and high copper/zinc ratio (≥1.563) was associated with a decreased overall 10-year survival and breast cancer-specific survival. We observed a clear correlation between high copper/zinc ratio levels and overall survival (HR 2.26 ) [hazard ratio] and breast cancer-specific survival (HR 2.07). The 10-year overall survival rate was 58.3% for women with the highest serum copper/zinc ratio quartile levels, compared to 83.1% among those in the lowest. The 10-year breast cancer-specific survival rate was 67.2% for women with the highest serum copper/zinc ratio quartile levels compared to 84.9% among those in the lowest quartile.	Finally, our results suggest the potential for zinc supplementation in breast cancer patients with low zinc levels. So far, zinc supplementation has been tested in a small study in a group of patients with colorectal cancer undergoing adjuvant chemotherapy. In that study, zinc supplementation during chemotherapy cycles increased antioxidant enzymes superoxide dismutase activity and maintained vitamin E concentrations [57]. There are currently no clinical trials on zinc supplementation in patients with breast cancer. Testing this hypothesis in breast cancer patients requires planning interventional studies with random selection in subgroups
https://www.auajournals.org/doi/abs/10.1097/JU.0000000000003080	3.5	Post-diagnostic low-dose zinc supplement use among nonmetastatic prostate cancer patients was associated with lower risk of lethal prostate cancer and all-cause mortality. A potential benefit of low-dose post-diagnostic zinc supplement for prostate cancer survival merits further study. [note , this only appears true for patients taking low dose zinc before diagnosis]	During a median follow-up of 11 years, we documented 527 lethal prostate cancer events and 3,198 all-cause deaths. Fifteen percent of men reported zinc supplement use post-diagnosis. Compared to nonusers, post-diagnostic zinc supplement use was associated suggestively with a lower risk of lethal prostate cancer (HR [95% CI], 0.82 [0.60-1.13]) and significantly with all-cause mortality (0.84 [0.74-0.96]). The inverse association was mostly observed among men who used post-diagnostic zinc supplements of 1-24 mg/d
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1025060/full	3.5	However, patients with gynecologic cancer exhibited significantly lower serum zinc concentrations following treatment, and patients with recurrent cancer were 4.8 times more likely to develop zinc deficiency than those with nonrecurrent cancer. A serum zinc concentration of <61 μg/dL was an independent predictor of recurrence. Once zinc deficiency occurred, the recurrence rate of zinc deficiency reached as high as 69%. Overall, our study indicates that zinc deficiency is associated with recurrence in gynecological cancers and physicians should monitor zinc levels during disease management.	Patients with gynecologic cancer are at higher risk for developing zinc deficiency after initial treatment completion, and patients with recurrent cancer are at higher risk of zinc deficiency. Low serum zinc concentration is an independent factor associated with cancer recurrence and poor prognosis. Furthermore, once zinc deficiency develops, the risk of zinc deficiency recurrence is high. Therefore, gynecologic oncologists should actively measure serum zinc concentrations to improve prognosis and maintain quality of life in patients with recurrent cancer.
https://www.biorxiv.org/content/10.1101/2025.02.08.637227v1.full	3.5	Our study demonstrates that CDKN2A/p16 itself drives inherent resistance to ICB. There are a handful of prior reports linking loss of CDKN2A expression, or 9p21 deletion, with changes in anti-tumor immunity and ICB response5,16–32. Here, we found that CDKN2A, and more specifically p16 alone, can drive differential ICB responses (Fig. S2). Consistent with our findings, an integrated analysis of immunogenomic and clinical data from over 1000 patients across 8 solid tumors demonstrated that 9p21 deletions, specifically encompassing CDKN2A and MTAP, were associated with decreased tumor immune responses and resistance to anti-PD1 or anti-PD-L1 monotherapy	In conclusion, the TME represents a competitive environment where access to nutrients, such as zinc, critically shapes the dynamics between tumor and immune cells. Our findings demonstrate that suppression of CDKN2A confers the ability to deplete zinc from the TME by upregulating the SLC39A9 transporter, impairing TAM function and reducing the efficacy of ICB therapy. This study highlights a previously unrecognized role of CDKN2A in maintaining a balanced TME metabolism that supports immune surveillance and therapeutic responses. In summary, our results identify an unexpected role for CDKN2A as a master regulator of zinc homeostasis, which impacts the TME and ICB therapy
https://www.mdpi.com/2227-9059/12/8/1775	3	When we combined selenium and zinc levels , we observed the hazard ratio for kidney cancer mortality to be 12.4. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR [hazard ratio] was 2.53. Our study suggests that selenium levels, combined selenium and zinc levels and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients.	We observed a statistically significant association of all-cause mortality when subgroups with low blood selenium levels were compared to patients with high selenium levels... this correlation was much stronger when only men were assessed ..We did not find a statistically significant association for zinc alone. When we combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV), we observed the hazard ratio for kidney cancer death to be 12.4.. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR was 2.53... Our study suggests that selenium levels, combined selenium and zinc levels and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients.
https://www.mdpi.com/2072-6643/16/4/527	3	Among the total number of 338 prostate cancer patients, there were 77 (22.8%) patients with corresponding extreme quartiles of Se and Zn, whereas 49 (14.5%) patients had corresponding first quartiles of Se and Zn [i.highest relative amounts] and 28 (8.28%) patients had corresponding fourth quartiles of Se and Zn . In the multivariable model, our findings show that individuals who were in both the lowest Se quartile and the lowest Zn quartile had almost a 21-fold lower chance of 5-year survival compared to patients in the highest Se and Zn quartiles (HR = 20.9)	Our results show the impact of combined Se and Zn levels on survival in prostate cancer patients. Even though the effect of Zn has already been well-established, our data strongly indicate that it is more beneficial to optimize both Se and Zn levels. Therefore, we are going to establish a trial to prove this statement. Certainly, such a trial should be based on careful, systematic measurements of Se and Zn serum levels. At the same time, we want to draw the attention of scientists around the world to conduct similar studies to determine the best element levels for people in different regions of the world, knowing that background levels of Se and Zn vary from continent to continent.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10772688/	3	The response (complete plus partial response) rates were 24% (4/17) and 38% (5/13) in the ND [non-deficient] and D [deficient] groups, respectively, in patients with gastric cancer (P=0.38). The response rates were 38% (5/13) and 40% (2/5) in the ND and D groups, respectively, in patients with colorectal cancer (P=0.95). The PFS and OS did not differ between the ND and D groups in patients with gastric or colorectal cancer	The proportion of zinc deficiency before first-line chemotherapy with FPOX in patients with gastric and colorectal cancer is high at approximately 40%, relative to that reported in the Japanese literature on voluntary health checkups at 0.4–0.6% (15). This indicated that these patients were highly likely to be in a D state before chemotherapy. This may be due to decreased zinc intake and absorption, inflammation, and downregulation of ZRT and IRT-like proteins (ZIP; a zinc transporter) in cancers (16-18). Low zinc intake is also reportedly related to the risk of gastrointestinal cancer, and cancer biology appears to be strongly associated with zinc intake
https://www.tandfonline.com/doi/full/10.4161/cbt.27633	3	The potential for efficacious zinc treatment and possible prevention is even more plausible for HCC [liver cancer] than for other cancers. The implications of zinc in relation to the association of chronic liver disease/cirrhosis with development of HCC described above offers another potential benefit of zinc treatment, which is not represented in other cancers. The hypozincemia and suppressed bioavailability of zinc for the liver parenchyma pose a relationship that does not exist in other cancers. An increased bioavailability of zinc to the liver in subjects with developing cirrhosis could suppress the exacerbated development of malignancy resulting from deficient delivery of zinc to the hepatocytes, premalignant cells, and/or early stage malignant cells. Some studies have indicated the potential effectiveness of oral zinc supplement to increase the zinc levels of the hypozincemia resulting from cirrhosis, which might also suppress the development of the associated HCC... Thus, the rationale exists in support of the potential zinc therapeutic approach for HCC.	The cytotoxic/tumor suppressor effect of zinc provides a rationale for a potential zinc treatment chemotherapeutic approach for HCC warrants further research. However, appropriate conditions that represent the zinc status as exists in human HCC must be employed in the experimental studies. The authors recognize that some of their concepts of the implications of zinc applied to HCC will be subject to evaluation and criticism; which should stimulate additional ideas and insight. Hopefully, this presentation provides the background and the rationale for the important implication and indispensible role of the zinc relationship in the development and progression of HCC; and will bring attention to the need for its expanded research support that will advance the understanding of HCC, its early detection, and its treatment and possible prevention.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5183570/	3	ZIP/Zn downregulation is a clinically established common event in prostate, hepatocellular and pancreatic cancers. 2. Compelling evidence supports the plausibility that a zinc treatment regimen will prevent development of malignancy and termination of progressing malignancy in these cancers; and likely other carcinomas that exhibit decreased zinc. 3. Scientifically-unfounded issues that oppose this ZIP/Zn relationship have introduced bias against support for research and funding of a zinc treatment approach.	The consistent and extensive clinical and experimental evidence overwhelmingly demonstrates that decreased zinc and the downregulation of the functional ZIP-family zinc uptake transporter (i.e. ZIP/Zn transformation) is a common event in the development and progression of PrCa, HCC, and PanCa. When such evidence has been developed in accord with the principles of the scientific method, we refer to this as ‘scientifically credible’ evidence. Moreover, no comparable scientifically credible evidence exists that opposes or contradicts this concept.
https://link.springer.com/article/10.1007/s12011-023-03818-6	3	Given the important role of zinc in a wide range of enzymatic reactions and physiological processes, zinc deficiency has been identified in a variety of diseases, notably cancer. In recent years, multiple meta-analyses and reviews looking at zinc levels in individual cancer types have been published, as have a plethora of primary studies demonstrating a link between low zinc levels and specific types of cancer. In this review, we summarize recent evidence implicating low zinc concentrations in serum or tissues as a characteristic in a wide range of cancers. We also discuss preliminary findings indicating that zinc level measurement could ultimately become a useful clinical tool for cancer diagnosis and predicting outcomes in patients with cancer	Clinically, it would be beneficial to explore the relationship between serum zinc levels and local zinc concentrations in patients with cancer, as well as the reliability of serum zinc levels as a biomarker of carcinogenesis risk and cancer patient prognosis. Finally, prospective clinical studies should be carried out to determine the prognostic benefits of zinc supplementation. Given the universality of zinc deficiency in cancer, gaining a greater understanding of the molecular basis and clinical impact of this association is likely to yield substantial benefits for human health.
https://www.mdpi.com/2218-273X/11/6/865	3	The level of zinc in the serum is an important prognostic factor in laryngeal cancer. The influence of serum zinc levels on survival in laryngeal cancer patients can be multiplied if correlated with adequate antioxidant enzymes polymorphisms: SOD2 TC/TT and CAT CC. A total of 86% of all laryngeal cancer patients have at least one of those genotypes, suggesting survival is dependent on serum zinc level with a HR of 2.55; 40% have both, with a HR of 3.13. Zinc supplementation in those patients might have positive effect on survival. A total of 13% of patients have neither the SOD2 TC/TT nor CAT CC variant and in that particular subgroup zinc influence on survival seems to be the opposite, suggesting that those patients should be excluded from zinc supplementation.	The results from this study suggest that low levels of serum zinc at the time of diagnosis are associated with a significantly increased risk of death among laryngeal cancer patients who reside in Szczecin, Poland. The effect appeared to be continuous; that is, the risk of death declined continuously with increasing circulating levels of zinc and there was no apparent threshold value. Individuals in the lowest tertile of zinc had a 1.95-fold increased risk of dying during their follow-up period. Many reports exist regarding the zinc levels in cancer versus the corresponding normal tissues. Decreased levels of zinc in malignant tissues have been shown for pancreatic, hepatocellular, prostate, lung, colon, thyroid, kidney, gall bladder and ovarian cancers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045709/	3	With the progression of tumor, the expression of SLC39A8 decreased progressively. The prognosis of patients with low expression of SLC39A8 is significantly worse. Furthermore, we found that overexpression of SLC39A8 or treatment with low concentration of zinc chloride could effectively inhibit the proliferation, migration and invasion of ccRCC cells. Moreover, the inhibition effect of SLC39A8 overexpression could be enhanced by low concentration zinc supplement. Therefore, this study provides a novel understanding for the role of SLC39A8/zinc in the regulation of ccRCC progression. These findings provide a new direction and target for progressive ccRCC drug development and combination therapy strategies.	In this [lab study not clinical trial in patients] study, the zinc supplementation experiments confirmed that the treatment with low concentration of zinc chloride could effectively inhibit the proliferation and colonies formation of ccRCC cells. In addition, overexpression of SLC39A8 could significantly inhibit 786-O and OSRC-2 cells proliferation, invasion and migration, and zinc supplementation could satisfactorily enhance this inhibitory effect. Western blotting experiments also confirmed that SLC39A8/zinc could inhibit the EMT of ccRCC cells. Based on these results and existing literatures, we propose a possible mechanism that SLC39A8/zinc inhibit the proliferation, invasion and migration of ccRCC cells
https://aacrjournals.org/cebp/article/16/8/1682/176858/Levels-of-Zinc-Selenium-Calcium-and-Iron-in-Benign	3	The associations were weakened by mutual adjustment. Furthermore, after stratification by menopausal status, the positive association between iron and breast cancer was confined to postmenopausal women (highest versus lowest quintile: OR, 2.77; 95% CL, 1.25, 6.13; Ptrend = 0.008), whereas the associations for zinc, calcium, and selenium did not differ by menopausal stratum. In conclusion, our data raise the possibility that relatively high levels of zinc, iron, and calcium in benign breast tissue may be associated with a modest increase in risk of subsequent breast cancer.	In conclusion, our data do not support the hypothesis that levels of zinc, calcium, and selenium are associated with a decrease in breast cancer risk, and indeed, raise the possibility that zinc, calcium, and iron may be associated with a modest increase in risk of subsequent breast cancer among women with benign breast disease
https://www.mdpi.com/2072-6643/14/13/2575	3	This study found no overall evidence of an effect of pre-diagnostic zinc on recurrence-free, breast cancer-specific or overall survival. However, better breast cancer-specific and overall survival were seen for intermediate/high zinc intake in the group with high phosphorus intake.	Our study showed better BCSS and OS for intermediate/high zinc intake in the group with high phosphorus intake. It is well–known that phosphorus, in the form of phytate, inhibits zinc absorption by forming insoluble complexes in the gastrointestinal tract that cannot be absorbed due to the absence of intestinal phytase enzymes [1,9]. Indeed, a meta-analysis by Bel-Serrat et al. (2014), including 30 studies, revealed an overall reduction of fractional zinc absorption by 45% of the control meals when the phytate/zinc molar ratio of the diet was greater than 15 [28]. In addition to phosphorus, other factors have been identified to have a possible effect on serum/plasma zinc levels, such as time of day [29], albumin levels [30] and infection [31]. It can be hypothesized that an effect of zinc on breast cancer prognosis might be seen only when zinc levels are reduced by external factors
https://www.sciencedirect.com/science/article/pii/S0002916523022153	3	Dietary zinc intake was associated with lower prostate cancer mortality, with a comparison of men in the highest quartile (>15.6 mg/d) with those in the lowest quartile of zinc intake (HR: 0.64; 95% CI: 0.44, 0.94; P for trend = 0.05). Zinc intake did not appear to significantly reduce the risk of death from other causes (HR: 0.92; 95% CI: 0.64, 1.33; P for trend = 0.66), although there was a 22% nonsignificant reduction in risk of all-cause mortality. On stratification by stage at diagnosis (Table 3), the protective association with high zinc intake appeared restricted to men in whom the diagnosis of prostate cancer was made at an early stage. In men with localized tumors, those in the highest quartile of zinc intake were 76% less likely to die of their disease (95% CI: 0.09, 0.66; P for trend = 0.005) than were men in the lowest quartile	A protective role of zinc against prostate cancer has long been suspected because of support from biological and experimental evidence; however, such a role has not been clearly confirmed in epidemiologic studies. Most of these studies have examined zinc in relation to the risk of developing prostate cancer rather than in relation to endpoints of disease progression or survival. Our findings of an inverse association between dietary zinc and prostate cancer–specific mortality suggest that zinc may play an important role in prostate cancer outcomes, particularly in men with localized disease. Because of the current lack of corroborative evidence, our study results are not sufficient to recommend zinc supplements to men after a prostate cancer diagnosis
https://pubmed.ncbi.nlm.nih.gov/32587956/	3	The decrease in zinc is due to the down regulation of the ZIP-family zinc uptake transporter. These cells are as “ZIP-deficient/decreased zinc” malignancies. This provides a target for a chemotherapy that can restore the high zinc levels that will manifest cytotoxic effects in the malignant cells. In order to achieve this, a vehicle that facilitates the uptake and accumulation of zinc in the ZIP-deficient cells is required. The zinc ionophore, clioquinol, exhibits the properties that will provide these requirements. This is demonstrated by the treatment of a patient with 3% Clioquinol Cream, which successfully suppressed the progression of androgen-dependent prostate cancer.	All carcinomas are zinc-deficient malignancies. The higher zinc levels that exist in the normal cells are cytotoxic in the malignant cells. The decrease in zinc is due to the down regulation of the ZIP-family zinc uptake transporter. Therefore, the carcinomas are characterized as “ZIP-deficient/decreased zinc” malignancies. The restoration of high zinc levels in the malignant cells is a target for a zinc chemotherapy. This requires a vehicle to facilitate the uptake and accumulation of cytotoxic levels of zinc in the ZIP-deficient cells. The zinc ionophore, clioquinol, exhibits the properties that will achieve the above requirements. The treatment of a patient with 3% Clioquinol Cream successfully suppressed the progression of androgen-dependent prostate cancer.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5083243/	3	The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued.	Although the zinc status in metastatic and advanced hormone-independent prostate cancer has not been established, some existing evidence indicates the likelihood that the loss of zinc persists in the advanced stages of malignancy. Heijmink et al. [72] showed that citrate is absent in lymph node metastasis; and this would be indicative of decreased zinc. Kim et al. [73] reported that promotion of prostate cancer invasion and metastasis occurs by decreasing intracellular zinc levels. Compelling evidence is also provided by identification of the loss of citrate, zinc, and ZIP1 in the metastatic lymph nodes in TRAMP. Based on such evidence, it is reasonable to expect that a zinc treatment approach will increase zinc accumulation and its cytotoxic effects in metastatic cells.
https://www.sciencedirect.com/science/article/pii/S2213231723001295?via%3Dihub	3	A higher copper/zinc ratio was associated with lower overall survival after breast cancer diagnosis. Comparing patients with a copper/zinc ratio in quartile 4 vs 1, the crude HR was 2.29 (1.65–3.19) (Ptrend <0.01) and the fully adjusted HR was 1.58 (1.11–2.25) (Ptrend = 0.01). No overall associations were seen between serum copper or zinc levels on their own and survival after breast cancer diagnosis, although a tendency toward lower breast cancer survival was seen for higher copper levels and lower zinc levels.	We conclude that a higher serum copper/zinc ratio is associated with a poor overall survival after breast cancer diagnosis. No overall associations between either of these trace elements alone and breast cancer survival were seen; however, a tendency toward lower breast cancer survival was seen for higher copper levels and lower zinc levels. Hence, our findings provide evidence for the serum copper/zinc ratio as an independent prognostic indicator of breast cancer survival. Future intervention studies are needed to test whether breast cancer patients with a high copper/zinc ratio could benefit from zinc supplementation or treatment with copper chelators.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2869512/	3	After 6 mo of supplementation, the intake of zinc, compared with intake of placebo, increased the concentrations of plasma zinc and decreased the concentrations of plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, and malondialdehyde and hydroxyalkenals (MDA+HAE) in elderly subjects. Regression analysis showed that changes in concentrations of plasma zinc were inversely associated with changes in concentrations of plasma hsCRP, MCP-1, VCAM-1, and MDA+HAE after 6 mo of supplementation	Mean (±SD) concentrations of plasma hsCRP before supplementation compared with those after supplementation with zinc were 2.46 ± 1.91 and 1.90 ± 1.51 μmol/L (P = 0.015), respectively. Compared with the placebo group, zinc-supplemented elderly subjects showed a significant change (post- minus presupplementation) in plasma hsCRP concentrations after 6 mo of supplementation (ΔP = 0.015; Table 2). Plasma IL-6 concentrations before supplementation compared with those after supplementation with the placebo significantly increased (P = 0.026). Plasma IL-6 concentrations before supplementation compared with those after supplementation with zinc decreased significantly
https://pmc.ncbi.nlm.nih.gov/articles/PMC2664741/	3	Ten-year average intake of supplemental zinc was not associated with a reduced prostate cancer risk overall (adjusted hazard ratio (HR) = 0.82 (95% confidence interval (CI) 0.58-1.14) for >15mg/day versus non-use, p for trend = 0.44); however, risk of advanced prostate cancer (regionally invasive or distant metastatic, n=123) decreased with greater intake of supplemental zinc (adjusted HR = 0.34 (95% CI 0.13-1.09) for 10-year average intake >15mg/day vs. non-use, p for trend = 0.04). Dietary zinc was not associated with prostate cancer.	In this large population-based cohort study, we observed that ten-year average intake of supplemental zinc was associated with a small, non-statistically significant reduced risk of prostate cancer overall. However, risk of advanced prostate cancer (regionally invasive or distant metastatic) decreased significantly with greater intake of supplemental zinc. Dietary zinc and total zinc intake (diet plus10-yr average supplemental zinc) were not associated with prostate cancer risk
https://pubmed.ncbi.nlm.nih.gov/35946077/	3	In meta-analyses with random-effect models, Zn supplements were shown to lead to a significant reduction in the level of post-trial fasting blood glucose, HbA1c and HOMA-IR, but not in the serum insulin level. These results had moderate certainty of evidence. Trial duration contributed to the heterogeneity in the results of fasting blood glucose and HbA1c and diabetes type specified contributed to the heterogeneity in HOMA-IR and serum insulin level. In the two-sample MR analysis, with two SNP, Zn supplement was also significantly associated with a lower level of fasting glucose, among the general population	Among the T2D patients, the pooled MD was −27·68 mg/dl (95 % CI (−37·26, −18·11)), comparing Zn intervention to the control arm (Fig. 2(a)). Among the participants without specified diabetes type, the pooled MD was −28·17 mg/dl (95 % CI (−43·88, −12·45)). Both stratified analyses showed strong evidence of effect and the two types of trials were not significantly different (Test of group difference P = 0·96). The overall pooled MD showed that the Zn intervention had a significantly lower level of fasting blood glucose at the end of the trial, compared with the control arm (MD: −26·52, 95 % CI (−35·13, −17·91)). Regardless of the Risk-of-bias (ROB) of the trials, the overall pooled MD was −26·87 mg/dl
https://link.springer.com/article/10.1007/s10238-020-00677-6	2.5	In the study by Lin et al. , the 34 patients with nasopharyngeal carcinoma in the III or IV stage were analysed separately from the sample, which originally comprised 97 patients. These calculations showed significant differences. After 68 months, patients in the zinc arm showed better outcomes in terms of overall survival (zinc arm: 29%, placebo arm: 65%), disease-free survival (zinc arm: 41%, placebo arm: 76%,) and time to local recurrence compared to the placebo arm (zinc arm: 18%, placebo arm: n = 59%)	Zinc substitution is able to help in protection against radiotherapy-induced inflammation of oral and oropharyngeal mucosa. No improvement is given in cases of mucositis due to chemotherapy. We have registered trends to less loss of taste and dry mouth during radiotherapy as well as mucositis-related oral pain. Zinc has no impact on the survival of tumour patients, e.g. it will not decrease the effect of basis anti-cancer therapy.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01293/full	2.5	in prostate cancer tissue, mean zinc levels are decreased by up to 80%, and in prostatic tissue derived from BPH, zinc levels are decreased by more than 50% (38). In addition, a significant (on average, 44%) increase was observed in the urine zinc/creatinine levels in prostate carcinoma when compared to BPH, and a highly significant increase (on average, 53%) when compared with controls was found, hinting at increased zinc excretion. There was also already a significant increase in urine zinc excretion in men with BPH compared to men with a healthy prostate. This suggests that pathological conditions of the prostate gland in patients with BPH or carcinoma may be associated with an alteration in biochemical parameters such as a reduction in the level of tissue zinc, plasma zinc, and an increase in urinary zinc excretion (38). For example, a recent study found that PCa patients had markedly reduced plasma zinc levels and that a low zinc status was more pronounced within the severe grade and advanced PCa disease subgroups, suggesting that low zinc status is associated with PCa	In the light that more than half of men in their 60's suffer from BPH, which increases to 90% by 70–80 years of age, and the direct effects of zinc on normal or malignant prostate cells, the need of adequate zinc status in men for having a healthy prostate becomes evident. Prostate zinc levels are depending on circulating zinc concentrations that have to be considered (29), which puts a focus on maximizing cellular uptake of zinc in tissues and absorption of zinc in the intestines. It has been shown in several studies that older adults (older adults >50 years) frequently have low zinc status (44, 45). Although the daily requirement for zinc does not increase with age, lifestyle factors and a reduced capacity to absorb zinc, an increase in the likelihood of diseases that affect zinc utilization, and the use of drugs that may decrease the bioavailability of zinc may all contribute to putting older individuals at an increased risk for the development of a mild zinc deficiency
https://pmc.ncbi.nlm.nih.gov/articles/PMC7476080/	2.5	The correlation between zinc levels and cancer progression appears to be complicated and less conclusive. The general opinion is that zinc shows antioxidant and proapoptotic properties by decreasing oxidative stress and improving immune function, which serves a protective effect on cancer initiation35,36. Notably, in some specific tumors such as breast cancer, mentioned above, the accumulating zinc levels are also observed in malignant tissues29. An explanation for this phenomenon is that increased demands for zinc are required for tumor survival and growth. The elevated zinc levels may facilitate the progression and malignancies of breast cancer.	Increasing studies show that zinc affects the apoptosis and metabolism of prostate cells. The mechanisms include suppression of mitochondrial aconitase activity and citrate oxidation46,47, induction of mitochondrial apoptogenesis48, an increased Bax/Bcl-2 ratio49, induction of HIF-1α degradation, and a decreased expression of survivin50. In addition, zinc has been shown to suppress the metastatic potential of prostate cancer by inhibiting NF-κB signaling51,52, and suppressing the invasive potential of the proteolytic enzyme urokinase-type plasminogen activator, aminopeptidase N, and prostate specific antigen (PSA)53,54. Based on these observations, zinc supplementation may be an effective therapy for prostate cancer