We conducted a randomized, double-blind, placebo-controlled trial to explore how zinc gluconate affects migraine symptoms in women. Sixty participants, with an average age of 35, were given either 15 mg of zinc per day or a placebo for 12 weeks, allowing us to measure the impact on headache frequency, duration, and intensity.
The results were quite promising; zinc supplementation significantly reduced how often headaches occurred, shortened their duration, and decreased the severity of the migraines reported. Participants in the zinc group experienced notable improvements, as indicated by their responses to the headache severity scale and a disability assessment questionnaire.
Furthermore, we found that zinc also had a positive effect on certain health markers. The serum levels of low-density lipoprotein (LDL), total cholesterol, and high-sensitivity C-reactive protein (hs-CRP) decreased with zinc supplementation. However, we didn’t observe significant changes in triglycerides or high-density lipoprotein (HDL) levels after adjusting for baseline values.
In conclusion, zinc supplementation appears to hold beneficial effects on migraine severity and frequency, offering a potential alternative for those who seek relief from these debilitating headaches.
Read More
7
Zinc may aid migraine relief
Zinc Administration Favorably Affects Prophylactic Therapy-refractory Migraine Attacks: A Case Series.
We explored the impact of zinc on migraine headaches, particularly looking at its effectiveness for those who haven’t found relief from traditional preventive treatments. Our investigation involved four patients suffering from migraine attacks that were resistant to usual prophylactic therapies.
Each of these patients reported a notable improvement in the frequency and severity of their headaches after incorporating zinc supplements into their regimen. This suggests that zinc might serve as a beneficial alternative for those grappling with stubborn migraines.
While our findings are promising, it's crucial to recognize that further research is needed to firmly establish the efficacy of zinc replacement therapy in this context. Nevertheless, zinc administration could offer hope for individuals facing challenges with typical migraine treatment options.
Read More
8
Zinc intake may reduce migraines
Dietary zinc intake in relation to migraine among adults: a cross sectional study of NHANES 1999-2004.
We explored the connection between zinc intake and migraine through the analysis of cross-sectional data from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. Our aim was to determine if higher dietary zinc could reduce the prevalence of migraines among adults.
In our analysis, we discovered that individuals consuming higher amounts of zinc experienced fewer migraines. Specifically, when comparing participants with the lowest zinc intake to those in higher intake groups, we found significant reductions in migraine occurrence. For example, adjusting for other factors, those in the second and third zinc intake groups had a 27% and 28% lower odds of experiencing migraines, respectively.
We also noted that age plays a role in how zinc intake affects headache prevalence, suggesting that the benefits of dietary zinc may differ depending on age. Interestingly, in adults aged 20 to 50, the relationship between zinc and migraines was not straightforward, indicating a complex interaction.
Overall, this research highlights the potential benefits of increasing zinc in our diets for reducing migraine frequency, and serves as a reminder that dietary choices can have significant health implications.
Read More
Most Useful Reviews
9
Supports headache relief
4 people found this helpful
An excellent chelated form of zinc, well absorbed. I take one capsule daily with food during cold season. Caution: taking it on an empty stomach may cause headaches. It supports immunity and helps with acne due to zinc's anti-inflammatory effects. I take Zinc along with vitamins C and D3 to maintain my family's health. I recommend you stay healthy and happy!
Read More
9
Nighttime usage suggested
I recommend taking this at night to avoid headaches, as it has shown excellent results for me.
Read More
9
Headaches alleviated
I received this product quickly in good packaging. The capsules are quite large, but there's no problem swallowing them. I've taken it for 10 days alongside vitamins D3+K2, magnesium, and B6. I'm noticing significant benefits, including increased energy and my headaches have disappeared. Perfect for those involved in sports or following a diet.
We conducted a randomized, double-blind, placebo-controlled trial to explore how zinc gluconate affects migraine symptoms in women. Sixty participants, with an average age of 35, were given either 15 mg of zinc per day or a placebo for 12 weeks, allowing us to measure the impact on headache frequency, duration, and intensity.
The results were quite promising; zinc supplementation significantly reduced how often headaches occurred, shortened their duration, and decreased the severity of the migraines reported. Participants in the zinc group experienced notable improvements, as indicated by their responses to the headache severity scale and a disability assessment questionnaire.
Furthermore, we found that zinc also had a positive effect on certain health markers. The serum levels of low-density lipoprotein (LDL), total cholesterol, and high-sensitivity C-reactive protein (hs-CRP) decreased with zinc supplementation. However, we didn’t observe significant changes in triglycerides or high-density lipoprotein (HDL) levels after adjusting for baseline values.
In conclusion, zinc supplementation appears to hold beneficial effects on migraine severity and frequency, offering a potential alternative for those who seek relief from these debilitating headaches.
Read More
8
Zinc intake may reduce migraines
Dietary zinc intake in relation to migraine among adults: a cross sectional study of NHANES 1999-2004.
We explored the connection between zinc intake and migraine through the analysis of cross-sectional data from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. Our aim was to determine if higher dietary zinc could reduce the prevalence of migraines among adults.
In our analysis, we discovered that individuals consuming higher amounts of zinc experienced fewer migraines. Specifically, when comparing participants with the lowest zinc intake to those in higher intake groups, we found significant reductions in migraine occurrence. For example, adjusting for other factors, those in the second and third zinc intake groups had a 27% and 28% lower odds of experiencing migraines, respectively.
We also noted that age plays a role in how zinc intake affects headache prevalence, suggesting that the benefits of dietary zinc may differ depending on age. Interestingly, in adults aged 20 to 50, the relationship between zinc and migraines was not straightforward, indicating a complex interaction.
Overall, this research highlights the potential benefits of increasing zinc in our diets for reducing migraine frequency, and serves as a reminder that dietary choices can have significant health implications.
Read More
8
Zinc may help reduce migraines
Dietary zinc intake and migraine in adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004.
We explored how dietary zinc intake relates to migraines by analyzing data from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. This cross-sectional study focused on adults who reported experiencing severe headaches or migraines.
Our findings indicated a noteworthy trend: higher intake of dietary zinc was associated with a lower likelihood of having migraines. Specifically, participants with greater zinc consumption—classified into various intake levels—showed a consistent decrease in the odds of experiencing migraine symptoms. For example, those in the highest quintile of zinc intake were 30% less likely to experience migraines compared to those with the lowest intake levels.
This suggests that increasing our zinc intake could be a beneficial strategy for managing migraines. While further research is needed to understand the precise mechanism, the anti-inflammatory and antioxidant properties of zinc may play a crucial role in reducing migraine occurrences.
Read More
8
Zinc chloride may reduce headaches
Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment.
We evaluated how zinc chloride, used in epipharyngeal abrasive therapy (EAT), might alleviate headaches among patients with long COVID. EAT involves applying zinc chloride to the lining of the epipharynx, where inflammation can linger after COVID-19.
Our study involved 58 patients who received EAT weekly for a month. Before and after the treatment, we measured the intensity of common long COVID symptoms, including fatigue and headaches, using a visual analog scale.
Interestingly, our findings showed that EAT helped reduce inflammation in the epipharynx and significantly improved not only headaches but also fatigue and attention disorders. This suggests that zinc chloride might play a role in easing headache symptoms associated with long COVID.
Overall, we believe this study highlights the potential of EAT as a new treatment avenue for managing long COVID symptoms, particularly headaches, which can often be debilitating for many.
Read More
8
Zinc improves headache symptoms
Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease: A Preliminary Report on 25 Patients.
We observed the use of intravenous calcium and zinc in patients diagnosed with gadolinium deposition disease, with a focus on how this treatment affected their headaches. In our preliminary report involving 25 patients, we noted significant improvements in headache symptoms among those receiving treatment, particularly with a regime of calcium-/zinc-diethylene triamine penta-acetic acid (DTPA).
Patients underwent three courses of treatment, and we measured their urinary gadolinium levels and self-reported symptoms before, during, and after these sessions. The findings revealed a noteworthy increase in Gd content in urine, indicating an effective chelation process, as well as moderate symptomatic relief.
Specifically, 13 patients reported a decrease in headache intensity, along with improvements in other symptoms like brain fog and bone pain. For those on a monthly treatment schedule, there were more significant benefits noted compared to the weekly treatment schedule.
Overall, while there was a transient worsening of symptoms in some patients at first—a phenomenon referred to as a "flare-up"—the outcome suggests that the combination therapy shows promise in alleviating headaches among individuals suffering from this perplexing condition.
An excellent chelated form of zinc, well absorbed. I take one capsule daily with food during cold season. Caution: taking it on an empty stomach may cause headaches. It supports immunity and helps with acne due to zinc's anti-inflammatory effects. I take Zinc along with vitamins C and D3 to maintain my family's health. I recommend you stay healthy and happy!
Read More
9
Nighttime usage suggested
I recommend taking this at night to avoid headaches, as it has shown excellent results for me.
Read More
9
Headaches alleviated
I received this product quickly in good packaging. The capsules are quite large, but there's no problem swallowing them. I've taken it for 10 days alongside vitamins D3+K2, magnesium, and B6. I'm noticing significant benefits, including increased energy and my headaches have disappeared. Perfect for those involved in sports or following a diet.
Read More
9
Immunity support noted
An excellent chelated form of zinc that I take one capsule daily with food during flu season. Avoid taking on an empty stomach to prevent headaches. It enhances immunity and helps with acne due to zinc's anti-inflammatory properties. I'm committed to my family's health during winter.
Read More
9
Tests for headache relief
The chelated form is an excellent, well-absorbed zinc. I take one capsule daily with food during cold season. Take care, as it may cause headaches or nausea if taken on an empty stomach. It supports immunity and helps with acne, improving recovery speed. I actively support my and my family’s health.
A headache is a common condition characterized by pain or discomfort in the head, scalp, or neck. It can vary in intensity, frequency, and duration, and is often classified into two primary categories: primary and secondary headaches. Primary headaches, such as tension-type headaches, migraines, and cluster headaches, are not caused by other medical conditions. Instead, they are conditions in themselves, often resulting from factors like stress, hormonal changes, or environmental triggers. Secondary headaches, on the other hand, are symptoms of an underlying issue, such as an infection, injury, or other medical conditions.
The experience of a headache can differ widely among individuals. Depending on the type, headaches can be throbbing or constant and may be accompanied by other symptoms like nausea, sensitivity to light, or aura effects before the headache strikes. Effective management strategies vary by headache type and may include over-the-counter pain relievers, lifestyle changes, and in some cases, prescription medications. Understanding the specific triggers and patterns related to your headaches can be crucial for prevention and treatment, so maintaining a headache diary may be beneficial for those experiencing frequent or severe episodes.
Zinc is a versatile metal known for its various applications in industry and health. It is a bluish-white metallic element represented by the symbol Zn and atomic number 30 on the periodic table. Zinc is primarily used for galvanizing steel to prevent rusting, in the manufacturing of alloys, and as a component in batteries. Additionally, zinc plays a crucial role in biological processes, making it an essential trace element in the human diet. It is involved in immune function, protein synthesis, wound healing, and DNA synthesis, highlighting its importance in maintaining overall health and well-being.
Zinc is an essential mineral known for its various health benefits, including immune support and anti-inflammatory properties. Some studies suggest that zinc may have a role in reducing the frequency and severity of headaches, particularly migraines, which can be linked to underlying nutritional deficiencies. Certain research indicates that individuals with lower levels of zinc may experience more frequent headaches, potentially due to its involvement in enzyme functions and neurotransmitter regulation.
However, while zinc supplementation could be beneficial for some, it's important to approach this method with caution. Self-diagnosing and treating headache disorders without professional guidance may lead to unintended side effects, particularly if taken in excessive amounts. If you're considering zinc as a potential remedy for headaches, consulting with a healthcare professional is advisable to determine the appropriateness based on your individual health status and specific headache type. So, while there’s a potential link between zinc and headache relief, more conclusive research is needed to establish zinc as a standardized treatment protocol.
Based on user reviews, the time it takes to see results from taking this supplement for headaches can vary significantly. Some users report experiencing noticeable benefits within just a few days. For instance, one user mentioned that their headaches disappeared after taking the supplement for only 10 days along with other vitamins, highlighting the effective nature of the product in addressing headaches quickly Read Review.
However, others have experienced initial side effects, such as headaches or nausea, which may take some time to adjust to. One user indicated that they noticed improved skin after two weeks, which they interpreted as a sign of the supplement's beneficial effects Read Review. Overall, while some users see fast results, it may take up to two weeks for others to notice significant improvements in headache symptoms.
Recent studies suggest that zinc supplementation holds promise in the management of headaches, particularly migraines. A systematic review indicated a positive role for zinc in alleviating migraine symptoms, though it emphasized the necessity for more comprehensive clinical trials to establish definitive efficacy [1]. In a clinical trial of 80 patients, those receiving zinc sulfate experienced a marked reduction in the frequency of migraine attacks compared to a placebo group, with an average of 2.55 fewer attacks [7]. Additionally, a randomized trial focusing on women showed that zinc supplementation significantly lowered headache frequency, duration, and severity, indicating that it may be a viable alternative for women seeking relief [6].
Moreover, observational studies have highlighted that individuals with higher dietary zinc intake consistently report fewer migraines compared to those with lower intake levels, suggesting that dietary adjustments might offer a preventative strategy against migraines [3]. Another study found that zinc chloride treatment helped reduce headache symptoms in long COVID patients, showing its potential role in a broader range of headache-related conditions [5]. Overall, while the data is encouraging, further research is essential to fully understand zinc's role in headache management and to determine optimal dosages and treatment protocols.
Users report a range of symptoms improvements after taking this chelated form of zinc, particularly concerning immunity and headaches. Many reviewers highlighted its efficacy in enhancing immune response during cold and flu seasons, with one user noting a significant boost in recovery speed alongside reduced headaches when combined with other vitamins Read Review. Additionally, several users emphasized that it effectively alleviates headaches when taken with food, while cautioning against taking it on an empty stomach to avoid adverse effects like headaches Read ReviewRead Review.
However, individual experiences may vary, as some users reported initial discomforts, such as headaches or nausea, that dissipated over time. One user, after a challenging start, noted an improvement in their skin and overall well-being two weeks into their regimen Read Review. While this zinc supplement seems to provide notable benefits for many, it's important to recognize that not everyone may experience the same effects, with some facing discomfort that may lead to discontinuing use altogether Read Review.
Users have reported varying experiences when combining this chelated zinc supplement with other vitamins for managing headaches. Many reviewers indicated that taking it alongside vitamins, particularly vitamin C and D3, can enhance its effectiveness. For instance, one user noted that after taking the zinc with vitamins D3+K2, magnesium, and B6 for ten days, their headaches had disappeared, marking a significant improvement Read Review. Another user mentioned that they successfully used zinc with vitamin C to alleviate headaches during the early stages of a cold, stressing how these combinations can bolster immune response while also helping with headache relief Read Review.
However, caution is advised as some users experienced headaches or nausea, especially when the supplement was taken on an empty stomach. One reviewer recommended taking the supplement at night to avoid such issues Read Review. Overall, while many users found that combining this zinc supplement with other vitamins provided significant headache relief and health benefits, individual responses can vary, with some individuals experiencing discomfort that led them to discontinue use Read Review.
Zinc has shown promise in alleviating migraine symptoms, with various studies exploring its effectiveness in treating headaches. A randomized, double-blind, placebo-controlled trial found that women supplemented with 15 mg of zinc per day experienced significant reductions in headache frequency, duration, and intensity over a 12-week period [6]. In another clinical trial involving 80 patients, participants taking zinc sulfate saw an average reduction of 2.55 migraine attacks compared to just 0.42 in the placebo group [7].
While these findings suggest that zinc supplementation may serve as a beneficial alternative for those struggling with migraines, it's important to note that consistent dosages and extensive clinical trials are still needed to confirm its efficacy. The doses used in these studies point towards a potential optimal intake of around 15 mg daily to effectively manage migraine symptoms. However, as the research matures, more definitive guidelines may emerge, establishing zinc’s role in headache management more firmly.
9
Headaches alleviated
I received this product quickly in good packaging. The capsules are quite large, but there's no problem swallowing them. I've taken it for 10 days alongside vitamins D3+K2, magnesium, and B6. I'm noticing significant benefits, including increased energy and my headaches have disappeared. Perfect for those involved in sports or following a diet.
7.5
Nausea indicates effectiveness
1 people found this helpful
Depending on my constitution, I experienced nausea and headaches initially. But I've noticed improved skin after two weeks of taking it, which I believe indicates the product contains beneficial ingredients.
9
Supports headache relief
4 people found this helpful
An excellent chelated form of zinc, well absorbed. I take one capsule daily with food during cold season. Caution: taking it on an empty stomach may cause headaches. It supports immunity and helps with acne due to zinc's anti-inflammatory effects. I take Zinc along with vitamins C and D3 to maintain my family's health. I recommend you stay healthy and happy!
9
Nighttime usage suggested
I recommend taking this at night to avoid headaches, as it has shown excellent results for me.
0
Not suitable for all
I ordered this zinc for myself, but I suffered terrible headaches and nausea after taking it. I stopped for three days and gave it to my mother, who experiences no issues. It may not suit everyone.
7.5
Headache prevention confirmed
This inexpensive zinc really works! I take it with vitamin C at the initial stage of a cold, and it has been effective in preventing illness and relieving headaches. I will definitely order more!
7
Zinc's role in migraine management
Zinc as An Emerging Therapy in the Management of Migraine: A Systematic Review.
We explored the impact of zinc in managing migraines, which are often debilitating headaches that many people experience. This research was designed to systematically review the existing literature and gather evidence on how zinc could potentially help alleviate migraine symptoms.
Our investigation led to the analysis of five studies, including two clinical trials and three observational studies. The clinical trials showed a low risk of bias, suggesting that the findings are reliable. Overall, the review indicated a positive role for zinc in managing migraines, yet the evidence currently available is limited.
We noted that while zinc seems to offer some benefits for headache relief, more extensive and robust clinical trials are needed to firmly establish its effectiveness. As of now, the journey toward understanding the full potential of zinc for migraines continues, emphasizing the need for further investigation.
7
Zinc may lower migraine frequency
Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.
We conducted a randomized clinical trial involving 80 patients to explore the effects of zinc supplementation on migraine headaches. Over the course of eight weeks, participants received either zinc sulfate or a placebo, allowing us to identify any significant differences in migraine characteristics.
Our findings revealed that those taking zinc experienced a notable drop in the frequency of migraine attacks compared to the placebo group. Specifically, the zinc group had an average reduction of 2.55 attacks, while the placebo group saw a minor reduction of just 0.42 attacks.
Furthermore, we observed some reduction in headache severity among those taking zinc, though this effect lost statistical significance when accounting for other factors. It's also important to note that zinc supplementation did not change the duration of the migraine attacks or daily headache impact for the participants.
Overall, our research suggests that zinc supplementation could be beneficial in reducing the frequency of migraine attacks. However, further studies over longer periods and with varying dosages of zinc would be useful to fully understand its potential.
9
Zinc reduces migraine symptoms
Assessing the Effect of Zinc Supplementation on the Frequency of Migraine Attack, Duration, Severity, Lipid Profile and hs-CRP in Adult Women.
We conducted a randomized, double-blind, placebo-controlled trial to explore how zinc gluconate affects migraine symptoms in women. Sixty participants, with an average age of 35, were given either 15 mg of zinc per day or a placebo for 12 weeks, allowing us to measure the impact on headache frequency, duration, and intensity.
The results were quite promising; zinc supplementation significantly reduced how often headaches occurred, shortened their duration, and decreased the severity of the migraines reported. Participants in the zinc group experienced notable improvements, as indicated by their responses to the headache severity scale and a disability assessment questionnaire.
Furthermore, we found that zinc also had a positive effect on certain health markers. The serum levels of low-density lipoprotein (LDL), total cholesterol, and high-sensitivity C-reactive protein (hs-CRP) decreased with zinc supplementation. However, we didn’t observe significant changes in triglycerides or high-density lipoprotein (HDL) levels after adjusting for baseline values.
In conclusion, zinc supplementation appears to hold beneficial effects on migraine severity and frequency, offering a potential alternative for those who seek relief from these debilitating headaches.
8
Zinc intake may reduce migraines
Dietary zinc intake in relation to migraine among adults: a cross sectional study of NHANES 1999-2004.
We explored the connection between zinc intake and migraine through the analysis of cross-sectional data from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. Our aim was to determine if higher dietary zinc could reduce the prevalence of migraines among adults.
In our analysis, we discovered that individuals consuming higher amounts of zinc experienced fewer migraines. Specifically, when comparing participants with the lowest zinc intake to those in higher intake groups, we found significant reductions in migraine occurrence. For example, adjusting for other factors, those in the second and third zinc intake groups had a 27% and 28% lower odds of experiencing migraines, respectively.
We also noted that age plays a role in how zinc intake affects headache prevalence, suggesting that the benefits of dietary zinc may differ depending on age. Interestingly, in adults aged 20 to 50, the relationship between zinc and migraines was not straightforward, indicating a complex interaction.
Overall, this research highlights the potential benefits of increasing zinc in our diets for reducing migraine frequency, and serves as a reminder that dietary choices can have significant health implications.
8
Zinc chloride may reduce headaches
Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment.
We evaluated how zinc chloride, used in epipharyngeal abrasive therapy (EAT), might alleviate headaches among patients with long COVID. EAT involves applying zinc chloride to the lining of the epipharynx, where inflammation can linger after COVID-19.
Our study involved 58 patients who received EAT weekly for a month. Before and after the treatment, we measured the intensity of common long COVID symptoms, including fatigue and headaches, using a visual analog scale.
Interestingly, our findings showed that EAT helped reduce inflammation in the epipharynx and significantly improved not only headaches but also fatigue and attention disorders. This suggests that zinc chloride might play a role in easing headache symptoms associated with long COVID.
Overall, we believe this study highlights the potential of EAT as a new treatment avenue for managing long COVID symptoms, particularly headaches, which can often be debilitating for many.
References
Singhal S, Dutta SB, Bansal S, Dutta S, Shah RB. Zinc as An Emerging Therapy in the Management of Migraine: A Systematic Review. Neurol India. 2024;72:934. 10.4103/neurol-india.Neurol-India-D-23-00337
Fukazawa R, Ishii R, Higashimoto Y, Hanya M, Shimizu Y, et al. Zinc Administration Favorably Affects Prophylactic Therapy-refractory Migraine Attacks: A Case Series. Intern Med. 2024;63:1631. 10.2169/internalmedicine.2111-23
Zheng H, Tian S, Wu L, Zhong X, Liu M, et al. Dietary zinc intake in relation to migraine among adults: a cross sectional study of NHANES 1999-2004. Nutr Neurosci. 2024;27:667. 10.1080/1028415X.2023.2243678
Liu H, Wang Q, Dong Z, Yu S. Dietary zinc intake and migraine in adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004. Headache. 2023;63:127. 10.1111/head.14431
Imai K, Yamano T, Nishi S, Nishi R, Nishi T, et al. Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment. Viruses. 2022;14. 10.3390/v14050907
Mazaheri M, Aghdam AM, Heidari M, Zarrin R. Assessing the Effect of Zinc Supplementation on the Frequency of Migraine Attack, Duration, Severity, Lipid Profile and hs-CRP in Adult Women. Clin Nutr Res. 2021;10:127. 10.7762/cnr.2021.10.2.127
Ahmadi H, Mazloumi-Kiapey SS, Sadeghi O, Nasiri M, Khorvash F, et al. Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial. Nutr J. 2020;19:101. 10.1186/s12937-020-00618-9
Semelka RC, Ramalho M, Jay M, Hickey L, Hickey J. Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease: A Preliminary Report on 25 Patients. Invest Radiol. 2018;53:373. 10.1097/RLI.0000000000000453