We examined the effects of vitamin C on pneumonia caused by the influenza virus, specifically the H1N1 strain, in mice under stress. The study found that when exposed to restraint stress, the mice experienced increased mortality and more severe pneumonia symptoms.
However, by giving them oral vitamin C at doses of 125 and 250 mg/kg, we observed a significant reduction in these severe outcomes. Vitamin C seemed to modulate the expression of certain genes related to the immune response, such as MAVS and IRF3, and increased the expression of NF-κB, which plays a key role in the body's antiviral defense.
Our research suggested that vitamin C's protective effects might stem from its ability to inhibit excess cortisol production in the adrenal gland, which is often elevated due to stress. By lowering cortisol levels, vitamin C may help reduce susceptibility to influenza infections, making it a potential ally during the flu season, especially for those experiencing stress.
Through these findings, we highlighted a new mechanism for how vitamin C can be beneficial during influenza infections, particularly for those who are feeling overwhelmed.
Read More
8
Vitamin C triterpene flu inhibitors
Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.
We recently explored the potential of novel compounds that are combinations of L-ascorbic acid, commonly known as vitamin C, and pentacyclic triterpenes in battling the flu. The study focused on compounds we created and tested against the influenza virus in MDCK cells, particularly looking at their effectiveness and any possible side effects.
Among all the compounds we evaluated, one stood out: the 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid-betulinic acid conjugate. It displayed significant anti-influenza activity with an effective concentration (EC50) of just 8.7 μM and was not toxic to the cells used in our testing. This suggests that combining vitamin C with these triterpenes might enhance their ability to fight the flu virus, marking an exciting avenue for further research.
We also discovered that this particular compound acts early in the influenza lifecycle, interfering with the virus's ability to attach to cells. We confirmed this by observing that it inhibited the hemagglutination—a crucial step that allows the virus to spread. Our findings indicate that L-ascorbic acid-conjugated triterpenes hold promise as potential anti-influenza agents, specifically targeting viral entry and enhancing the effectiveness of treatment strategies.
Read More
4
Vitamin C shows moderate influenza inhibition
Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus.
We investigated the effects of various compounds, including vitamin C, on the neuraminidase (NA) activity of influenza viruses, specifically H1N1 and H5N2. Neuraminidase is crucial for the virus as it helps release new viral particles from infected cells, making it a key target for antiviral treatments.
In this study, we focused on five different compounds that are structurally distinct from sialic acid, which is the natural substrate of neuraminidase. Among those tested, vitamin C was one of the compounds alongside others like acetyl phenylalanylmethionine and propanoic acid derivatives. We found that these compounds inhibited NA activity, but the degree of inhibition varied.
Notably, the inhibition we observed was in the millimolar range, which suggests that while there is some effect, the affinity of vitamin C to inhibit neuraminidase is moderate compared to the reference drug zanamivir. The IC values for the compounds ranged from 6.4 to 73 mM, indicating that they are not as potent as zanamivir.
Overall, our study presents vitamin C and other small organic molecules as potential lead compounds for developing new neuraminidase inhibitors, even if vitamin C’s impact on flu remains to be clarified as part of a broader analysis of multiple compounds.
Read More
Most Useful Reviews
10
Prevented flu altogether
116 people found this helpful
Vitamin C is crucial for my health and wellbeing, particularly in its crystalline form. I appreciate this product as it dissolves easily, making it a pleasant experience to consume. I have been using this brand for about a year with excellent results, but I have taken Vitamin C supplements for over 64 years, and remarkably, I have never contracted the flu. I take massive doses of 8,000 to 10,000 mg daily and feel great. As I approach my 80th birthday on 14th April, I remain medication-free, and I thank the Almighty Creator every day.
Read More
9
Family effective
95 people found this helpful
I purchased this vitamin C for my family during the flu season. It's very effective and of top quality; both colds and flu pass quickly. I particularly liked that it's in powder form, making it convenient for everyone to take.
Read More
9
Long-lasting effects
56 people found this helpful
Excellent vitamins! After any flu or SARS, it lasts a long time; pure vitamin C without impurities. It's sour, but a great choice for boosting immunity.
We set out to discover how red ginseng and vitamin C work together to enhance immune cell function and fight off viral infections like the flu. In our investigation, we treated human immune cells and specific types of mice unable to produce vitamin C, looking closely at their reaction to influenza A virus/H1N1.
Our findings were quite promising. We observed that both red ginseng and vitamin C elevated the activation levels of immune cells, particularly T-cells and natural killer (NK) cells, known for their vital role in combating viruses. This combination not only helped boost immune cell activity but also reduced lung inflammation caused by the influenza virus, which is crucial for better survival rates during infections.
In cases where vitamin C levels were low in a specific mouse model, we noted that the added nutrients significantly improved their condition. They experienced reduced viral load and inflammation in their lungs after receiving red ginseng and vitamin C, compared to those without this supplementation. These insights suggest that while red ginseng and vitamin C collectively support immune health, the interplay of these substances can be crucial in managing flu infections effectively.
Read More
8
Vitamin C triterpene flu inhibitors
Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.
We recently explored the potential of novel compounds that are combinations of L-ascorbic acid, commonly known as vitamin C, and pentacyclic triterpenes in battling the flu. The study focused on compounds we created and tested against the influenza virus in MDCK cells, particularly looking at their effectiveness and any possible side effects.
Among all the compounds we evaluated, one stood out: the 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid-betulinic acid conjugate. It displayed significant anti-influenza activity with an effective concentration (EC50) of just 8.7 μM and was not toxic to the cells used in our testing. This suggests that combining vitamin C with these triterpenes might enhance their ability to fight the flu virus, marking an exciting avenue for further research.
We also discovered that this particular compound acts early in the influenza lifecycle, interfering with the virus's ability to attach to cells. We confirmed this by observing that it inhibited the hemagglutination—a crucial step that allows the virus to spread. Our findings indicate that L-ascorbic acid-conjugated triterpenes hold promise as potential anti-influenza agents, specifically targeting viral entry and enhancing the effectiveness of treatment strategies.
Read More
8
Vitamin C mitigates flu pneumonia
A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice.
We examined the effects of vitamin C on pneumonia caused by the influenza virus, specifically the H1N1 strain, in mice under stress. The study found that when exposed to restraint stress, the mice experienced increased mortality and more severe pneumonia symptoms.
However, by giving them oral vitamin C at doses of 125 and 250 mg/kg, we observed a significant reduction in these severe outcomes. Vitamin C seemed to modulate the expression of certain genes related to the immune response, such as MAVS and IRF3, and increased the expression of NF-κB, which plays a key role in the body's antiviral defense.
Our research suggested that vitamin C's protective effects might stem from its ability to inhibit excess cortisol production in the adrenal gland, which is often elevated due to stress. By lowering cortisol levels, vitamin C may help reduce susceptibility to influenza infections, making it a potential ally during the flu season, especially for those experiencing stress.
Through these findings, we highlighted a new mechanism for how vitamin C can be beneficial during influenza infections, particularly for those who are feeling overwhelmed.
Read More
7
Vitamin C's promise against flu
Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.
We examined how vitamin C supplementation can impact flu incidence and symptom duration. Our analysis of clinical studies indicated that vitamin C does show promise in reducing the risk of acute respiratory infections, including flu. Specifically, vitamin C reduced the likelihood of catching an acute respiratory infection by approximately 4% (risk ratio of 0.96).
Additionally, we observed that vitamin C also helps shorten the duration of flu symptoms by around 9%. This effect seemed to be more pronounced in men and people from middle-income countries, highlighting the complexity of health factors influenced by gender and socio-economic status.
Overall, while the findings suggest vitamin C can be a modicum of hope in managing flu symptoms, it isn't a standalone solution. Our results advocate for more research to fully understand the impact of vitamin C, especially in the context of the ongoing challenges posed by various respiratory viruses, including influenza.
Read More
4
Vitamin C shows moderate influenza inhibition
Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus.
We investigated the effects of various compounds, including vitamin C, on the neuraminidase (NA) activity of influenza viruses, specifically H1N1 and H5N2. Neuraminidase is crucial for the virus as it helps release new viral particles from infected cells, making it a key target for antiviral treatments.
In this study, we focused on five different compounds that are structurally distinct from sialic acid, which is the natural substrate of neuraminidase. Among those tested, vitamin C was one of the compounds alongside others like acetyl phenylalanylmethionine and propanoic acid derivatives. We found that these compounds inhibited NA activity, but the degree of inhibition varied.
Notably, the inhibition we observed was in the millimolar range, which suggests that while there is some effect, the affinity of vitamin C to inhibit neuraminidase is moderate compared to the reference drug zanamivir. The IC values for the compounds ranged from 6.4 to 73 mM, indicating that they are not as potent as zanamivir.
Overall, our study presents vitamin C and other small organic molecules as potential lead compounds for developing new neuraminidase inhibitors, even if vitamin C’s impact on flu remains to be clarified as part of a broader analysis of multiple compounds.
Read More
User Reviews
USERS' SCORE
Good
Based on 60 Reviews
8.7
All Reviews
Positive Reviews
Negative Reviews
10
Prevented flu altogether
116 people found this helpful
Vitamin C is crucial for my health and wellbeing, particularly in its crystalline form. I appreciate this product as it dissolves easily, making it a pleasant experience to consume. I have been using this brand for about a year with excellent results, but I have taken Vitamin C supplements for over 64 years, and remarkably, I have never contracted the flu. I take massive doses of 8,000 to 10,000 mg daily and feel great. As I approach my 80th birthday on 14th April, I remain medication-free, and I thank the Almighty Creator every day.
Read More
9
Family effective
95 people found this helpful
I purchased this vitamin C for my family during the flu season. It's very effective and of top quality; both colds and flu pass quickly. I particularly liked that it's in powder form, making it convenient for everyone to take.
Read More
9
Long-lasting effects
56 people found this helpful
Excellent vitamins! After any flu or SARS, it lasts a long time; pure vitamin C without impurities. It's sour, but a great choice for boosting immunity.
Read More
10
Prevents illness
This is one of the best products I’ve acquired for the flu season. I swear by it and recommend it to all my family and friends. In the year I took it, I didn’t fall ill, not even with a cold.
Read More
10
Flu-free experience
Since I started taking this, I've not had the flu again! It's truly an excellent product.
The flu, short for influenza, is a contagious respiratory illness caused by influenza viruses. It affects the nose, throat, and sometimes the lungs, leading to a range of symptoms that can vary in severity. Common symptoms include fever, chills, muscle aches, cough, congestion, runny nose, headaches, and fatigue. The flu can lead to serious complications, particularly in vulnerable populations such as young children, the elderly, pregnant women, and those with underlying health conditions.
The flu virus spreads primarily through respiratory droplets when an infected person coughs, sneezes, or talks. It can also be transmitted by touching surfaces contaminated with the virus and then touching one's face. Vaccination is the most effective way to prevent the flu, and the vaccine is typically updated annually to provide protection against the most common circulating strains. In addition to vaccination, practicing good hygiene, such as frequent handwashing and respiratory etiquette, can help minimize the risk of infection.
Ascorbic acid, commonly known as vitamin C, is a water-soluble vitamin that is essential for various bodily functions, including the synthesis of collagen, the absorption of iron, and the maintenance of a healthy immune system. Found naturally in a variety of fruits and vegetables, especially citrus fruits, strawberries, kiwi, and bell peppers, it serves as a potent antioxidant, helping to protect cells from damage by free radicals. Given that the human body cannot synthesize ascorbic acid on its own, it must be obtained through diet or supplementation.
In addition to its fundamental role in supporting overall health, ascorbic acid has garnered interest for its potential benefits in skincare and wound healing. Topical applications of vitamin C can help reduce the appearance of fine lines and improve skin texture, making it a popular ingredient in various cosmetic formulations. Additionally, it plays a crucial role in the body's ability to repair tissues and produce important neurotransmitters. For those looking to boost their vitamin C intake, incorporating a variety of vitamin C-rich foods into your diet or considering a supplement can be effective strategies.
Ascorbic acid, commonly known as vitamin C, is often touted for its immune-boosting properties. While some studies suggest that high doses of vitamin C can reduce the duration and severity of cold symptoms, the evidence regarding its effectiveness for the flu specifically is less concrete. The flu is caused by the influenza virus, and ascorbic acid may not directly combat the virus itself. However, maintaining adequate levels of vitamin C is crucial for overall immune function, which could potentially help your body respond better to illnesses, including the flu.
If you're considering using ascorbic acid as a supplement for flu prevention or treatment, it's important to consult with a healthcare professional. They can provide guidance based on your individual health needs and advise on proper dosages. In general, while incorporating vitamin C-rich foods, like oranges, strawberries, and bell peppers, into your diet can be beneficial for your immune health, relying solely on ascorbic acid to combat the flu is not a substitute for vaccines, antiviral medications, or other proven preventive measures.
Based on user reviews, many individuals report experiencing positive results quickly after taking vitamin C for flu symptoms. For instance, one user noted that their cold was alleviated in as little as three days after starting the supplement (Read Review). Another reviewer remarked on the effectiveness of the vitamin C in alleviating symptoms when taken at the onset of illness (Read Review). Many users also emphasize the importance of starting the regimen promptly to see the best results.
Overall, it seems that users generally begin to notice a difference within a few days of consumption, particularly when the supplement is taken as soon as flu symptoms appear. Several reviewers even mention that consistent use can help prevent the flu altogether, further highlighting the product's potential effectiveness in enhancing immunity during flu season (Read Review). It’s clear from these testimonials that vitamin C could be a valuable ally in your quest to combat flu symptoms.
Vitamin C has garnered some attention in scientific circles for its potential role in combating flu symptoms and reducing the incidence of acute respiratory infections. A study indicated that vitamin C supplementation could lower the risk of catching an acute respiratory infection by approximately 4% and shorten the duration of flu symptoms by around 9% [1]. This suggests that while vitamin C is not a standalone solution for flu management, it may offer some benefits as an adjunctive treatment.
Moreover, a combination of vitamin C with other compounds, such as red ginseng, was found to elevate immune cell function and reduce lung inflammation from the flu, presenting further evidence for its immune-boosting properties [3]. Additionally, researchers explored novel compounds combining vitamin C with triterpenes that showed significant anti-influenza activity, suggesting that vitamin C may enhance the effectiveness of other treatments [4]. Overall, while there is emerging evidence supporting vitamin C's role in flu prevention and management, further research is necessary to fully understand its mechanisms and effectiveness in this context.
Based on user reviews, several individuals have reported significant improvements in their symptoms related to colds and flu after using vitamin C in powder form. Many users claim that they experience a faster recovery, with one reviewer noting that their cold symptoms disappeared in just three days after starting the supplement (Read Review), while another confirmed that the product effectively rescued them from a prolonged bout of flu when combined with fresh orange juice (Read Review). Several users have also emphasized the role of vitamin C in preventative measures, reporting that they or their families did not fall ill during peak flu season after regular use (Read Review).
Moreover, the convenience of the powder form has been highlighted as a contributing factor to its popularity, with users appreciating that it can be easily mixed into drinks or taken in diverse ways (Read Review). It's important to note, however, that individual experiences may vary, as some users found that they needed to take higher doses for optimal effects (Read Review). Overall, many users seem to agree that vitamin C is a promising addition to their flu-fighting arsenal, providing notable benefits in terms of immune support and symptomatic relief.
Based on user reviews, many individuals reported that combining vitamin C with other supplements proved beneficial in managing flu symptoms effectively. For instance, one user mentioned that they have been taking vitamin C alongside various other supplements for several years, and as a result, they have successfully maintained their health, remaining free from colds and influenza (Read Review). This suggests that users find synergy between vitamin C and complementary supplements, enhancing overall immune response and providing added protection during flu season.
Moreover, users highlighted the convenience of the powder form of vitamin C, making it easy to mix with other beverages, such as orange juice, to improve both taste and efficacy (Read Review). This adaptability may further encourage users to experiment with various combinations, facilitating a more proactive approach to flu prevention. Overall, reviewers suggest that integrating vitamin C with other immunity-boosting supplements can lead to substantial improvements in health resilience during flu outbreaks.
According to recent research, the optimal dosing for Ascorbic Acid, or Vitamin C, in treating flu symptoms tends to vary based on individual circumstances and specific study outcomes. One study indicated that in mice models, effective doses ranged from 125 to 250 mg/kg, which led to significant reductions in severe symptoms of H1N1 pneumonia, suggesting that higher doses can enhance immunity and provide protective benefits in stressed conditions [5]. However, human clinical data primarily suggest that daily supplementation of Vitamin C might help reduce the duration of flu symptoms by around 9%, indicating that consistent intake may play a crucial role in management [1].
While the specific "optimal" dose for humans continues to warrant further investigation, the evidence leans towards higher consumption for those facing stress, or as a preventive measure. It's also worth noting that in various studies, Vitamin C has shown potential as part of a combined treatment strategy, often in conjunction with other compounds like red ginseng, which appears to enhance immune response [3]. Hence, while precisely defining an optimal dose remains elusive, engaging with current guidelines and considering individual health contexts is essential for effectively incorporating Vitamin C into flu treatment protocols.
9
Effective for colds
A large package—it's a pity it doesn't come with a measuring spoon. For a cold, it gets you back on your feet in three days without needing to drink any pentafluicin powders. The taste reminds me of my childhood, when I took vitamin C in small sachets.
9
Helpful at onset of flu
This helps significantly at the onset of ARVI or flu. During such times, I consume a double dose. On regular days, I dissolve a tip of a teaspoon in a glass of water and drink it 3-5 times daily. The taste is pleasant, akin to regular water with a hint of acidity. If it's too sour for someone, you can simply add more water.
9
Strengthened immunity effect
Vitamin C has boosted my immunity, not only for me but for my family as well. We didn’t fall ill during the autumn or catch the flu, SARS, or COVID. We also managed to get through December unscathed. Thank you for this excellent product!
9
Effective relief
During the influenza season, this product was a hit! It rescued me after a prolonged bout of flu, especially when I mixed it with fresh orange juice. It genuinely works!
9
Family effective
95 people found this helpful
I purchased this vitamin C for my family during the flu season. It's very effective and of top quality; both colds and flu pass quickly. I particularly liked that it's in powder form, making it convenient for everyone to take.
9
Cold-free living
I've been taking vitamin C alongside other supplements for several years. This has allowed me to manage my health superbly, keeping me free of colds, corona, and influenza. Although it has a sour taste, it's manageable.
7
Vitamin C's promise against flu
Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.
We examined how vitamin C supplementation can impact flu incidence and symptom duration. Our analysis of clinical studies indicated that vitamin C does show promise in reducing the risk of acute respiratory infections, including flu. Specifically, vitamin C reduced the likelihood of catching an acute respiratory infection by approximately 4% (risk ratio of 0.96).
Additionally, we observed that vitamin C also helps shorten the duration of flu symptoms by around 9%. This effect seemed to be more pronounced in men and people from middle-income countries, highlighting the complexity of health factors influenced by gender and socio-economic status.
Overall, while the findings suggest vitamin C can be a modicum of hope in managing flu symptoms, it isn't a standalone solution. Our results advocate for more research to fully understand the impact of vitamin C, especially in the context of the ongoing challenges posed by various respiratory viruses, including influenza.
9
Immune booster for flu treatment
Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection.
We set out to discover how red ginseng and vitamin C work together to enhance immune cell function and fight off viral infections like the flu. In our investigation, we treated human immune cells and specific types of mice unable to produce vitamin C, looking closely at their reaction to influenza A virus/H1N1.
Our findings were quite promising. We observed that both red ginseng and vitamin C elevated the activation levels of immune cells, particularly T-cells and natural killer (NK) cells, known for their vital role in combating viruses. This combination not only helped boost immune cell activity but also reduced lung inflammation caused by the influenza virus, which is crucial for better survival rates during infections.
In cases where vitamin C levels were low in a specific mouse model, we noted that the added nutrients significantly improved their condition. They experienced reduced viral load and inflammation in their lungs after receiving red ginseng and vitamin C, compared to those without this supplementation. These insights suggest that while red ginseng and vitamin C collectively support immune health, the interplay of these substances can be crucial in managing flu infections effectively.
8
Vitamin C triterpene flu inhibitors
Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.
We recently explored the potential of novel compounds that are combinations of L-ascorbic acid, commonly known as vitamin C, and pentacyclic triterpenes in battling the flu. The study focused on compounds we created and tested against the influenza virus in MDCK cells, particularly looking at their effectiveness and any possible side effects.
Among all the compounds we evaluated, one stood out: the 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid-betulinic acid conjugate. It displayed significant anti-influenza activity with an effective concentration (EC50) of just 8.7 μM and was not toxic to the cells used in our testing. This suggests that combining vitamin C with these triterpenes might enhance their ability to fight the flu virus, marking an exciting avenue for further research.
We also discovered that this particular compound acts early in the influenza lifecycle, interfering with the virus's ability to attach to cells. We confirmed this by observing that it inhibited the hemagglutination—a crucial step that allows the virus to spread. Our findings indicate that L-ascorbic acid-conjugated triterpenes hold promise as potential anti-influenza agents, specifically targeting viral entry and enhancing the effectiveness of treatment strategies.
8
Vitamin C mitigates flu pneumonia
A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice.
We examined the effects of vitamin C on pneumonia caused by the influenza virus, specifically the H1N1 strain, in mice under stress. The study found that when exposed to restraint stress, the mice experienced increased mortality and more severe pneumonia symptoms.
However, by giving them oral vitamin C at doses of 125 and 250 mg/kg, we observed a significant reduction in these severe outcomes. Vitamin C seemed to modulate the expression of certain genes related to the immune response, such as MAVS and IRF3, and increased the expression of NF-κB, which plays a key role in the body's antiviral defense.
Our research suggested that vitamin C's protective effects might stem from its ability to inhibit excess cortisol production in the adrenal gland, which is often elevated due to stress. By lowering cortisol levels, vitamin C may help reduce susceptibility to influenza infections, making it a potential ally during the flu season, especially for those experiencing stress.
Through these findings, we highlighted a new mechanism for how vitamin C can be beneficial during influenza infections, particularly for those who are feeling overwhelmed.
References
Abioye AI, Bromage S, Fawzi W. Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis. BMJ Glob Health. 2021;6. doi:10.1136/bmjgh-2020-003176
Márquez-Domínguez L, Reyes-Leyva J, Herrera-Camacho I, Santos-López G, Scior T. Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus. Molecules. 2020;25. doi:10.3390/molecules25184248
Kim H, Jang M, Kim Y, Choi J, Jeon J, et al. Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection. J Pharm Pharmacol. 2016;68:406. doi:10.1111/jphp.12529
Wang H, Xu R, Shi Y, Si L, Jiao P, et al. Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors. Eur J Med Chem. 2016;110:376. doi:10.1016/j.ejmech.2016.01.005
Cai Y, Li YF, Tang LP, Tsoi B, Chen M, et al. A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. Biomed Res Int. 2015;2015:675149. doi:10.1155/2015/675149