Research - Flu
Broccoli Sprouts May Increase Activity of Natural Killer Cells in Response to Influenza Exposure
Müller L, Meyer M, Bauer RN, et al. Effect of broccoli sprouts and live attenuated influenza virus on peripheral blood natural killer cells: a randomized double-blind study. PLoS One. January 28, 2016;11(1):e0147742. doi: 10.1371/journal.pone.0147742.
Influenza infection, or the flu, is a common illness worldwide that sometimes causes serious illness and even death. Broccoli (Brassica oleracea var. italica, Brassicaceae) sprout homogenate (BSH) has been reported to attenuate viral replication and enhance immune responses of host organisms. BSH contains the compound sulforaphane, which has been shown to increase natural killer (NK) cell activity. These systemic lymphocytes trigger cytokine release and factor in the host's cytotoxic response. The live attenuated influenza virus (LAIV) vaccine is used as an experimental model in human subjects and has been shown to elevate nasal NK activity. This randomized, double-blind, placebo-controlled study investigated the impacts of BSH on immune cell activity, especially NK cell activity, in blood of nonsmoking, healthy subjects given LAIV.
Potential subjects were excluded if they smoked, since smoking affects immune response to LAIV, or had a flu vaccine or infection within a year prior to the study. The authors indicate that this study represents a portion of a larger study that did include smokers, with nasal responses to LAIV in smokers being separately published. Included subjects were randomly assigned to consume alfalfa (Medicago sativa, Fabaceae) sprout homogenate (ASH) as placebo or BSH once per day for 4 days. Daily dosage was 200 g of a shake containing 111 g of broccoli sprouts (reported to contain 100 µmol of sulforaphane) or ASH (said to contain "minimal" amounts of sulforaphane).
Broccoli sprouts were procured from Brassica Protection Products LLC (Baltimore, Maryland), while shakes were made by the Nutrition Research and Metabolism Core, University of North Carolina; Chapel Hill, North Carolina. On the second day of BSH or ASH treatment, nasal LAIV (FluMist®; MedImmune, Inc.; Gaithersburg, Maryland) was administered to subjects. Blood samples were collected on the first day of shake consumption, i.e., the day before LAIV administration (day −1), day 2, and day 21. Subjects were instructed to abstain from the consumption of other vegetables in the Brassicaceae family and anti-inflammatory drugs during the study period. Whole blood was analyzed by flow cytometry to quantify several types of immunity-related cells, and peripheral blood mononuclear cells were isolated for the detection of NK cells. NK cells were further analyzed for markers of activity and assayed for cytotoxicity. Nasal viral load also was measured using real-time reverse transcription polymerase chain reaction (RT-PCR).
This study took place during the flu season of 2012-2013. Overall, 42 subjects were randomly assigned to the ASH (n=23) or the BSH (n=19) group. After exclusion of subjects who developed respiratory illness or missed appointments, 21 subjects in the ASH group and 15 subjects in the BSH group received the treatments; in the ASH group, 1 additional subject dropped out early due to illness. Difficulties in sample collection or processing meant that in the ASH group, cell populations could be analyzed in only 11 subjects, and NK cell markers and cytotoxicity in 14 subjects. In the BSH group, cell populations and NK cell markers were analyzed in 11 subjects and cytotoxicity in 12. There were no adverse side effects reported, although 1 subject fainted during a blood draw. There were no statistically significant baseline differences in age, sex, race, or body mass index between groups; data were given only for 16 ASH subjects and 13 BSH subjects.
At day 2 and day 21, T cells and NKT cells (NK cells with similar activity to T cells) were significantly decreased in all subjects considered together as compared to day −1 (T cells: 26.5 ± 8.07 cells vs. 22.7 ± 5.27 cells, P=0.022; NKT cells: 1.65 ± 1.15 cells vs. 0.93 ± 0.61 cells, P=0.002). In all subjects, NKT cells were significantly decreased at day 21 as compared to day −1 (1.65 ± 1.15 cells vs. 1.23 ± 0.86 cells, P=0.036). Those in the BSH group had fewer NKT cells in blood on day 21 than the ASH group (P=0.041). [Note: Apparent formatting errors in one table suggest an opposite effect.] The authors suggest that T and NKT cells are reduced in blood because they are directed to the nasal mucosa in response to LAIV infection.
In all subjects, at day 2 as compared with day −1, a marker of reduced cytotoxicity in NK cells was significantly lowered (P=0.0084), suggesting that a greater proportion of NK cells were highly cytotoxic. Likewise, in all subjects at day 2, a marker of NK cell inhibition was significantly reduced (P=0.0007), a marker of NK cell cytotoxicity was significantly elevated (P=0.0095), and directly measured cytotoxic activity of NK cells was significantly increased (P=0.015). A marker of NK cell apoptotic potential was significantly increased on day 21 compared with day −1 only in those taking BSH (P=0.038). Differences in nasal viral load were not statistically significant.
In general, LAIV significantly decreased T cells and NKT cells in peripheral blood, while significantly increasing NK cell cytotoxicity. BSH had a significant effect on NKT cell number, as well as NK cell apoptotic potential. Reported results from both groups suggest that ASH also may have had bioactivity in subjects given LAIV, illustrating the necessity of careful selection of a placebo for future trials. [Note: Alfalfa has sometimes been used in folk medicine for respiratory infections.] Also, the clinical significance of measured effects is unclear. Future clinical studies would do well to include patients with the flu to ascertain efficacy of BSH on illness as opposed to vaccine response.
--Amy C. Keller, PhD
Source : American Botanical Council
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Echinaforce Hotdrink versus Oseltamivir in Influenza: A randomized, double-blind, double dummy, multicenter, non-inferiority clinical trial
Echinacea has antiviral activity against influenza viruses in vitro. This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new Echinacea formulation with the neuraminidase inhibitor Oseltamivir, the gold standard treatment of influenza.
Following informed consent, 473 patients with early influenza symptoms (≤48h) were recruited in primary care in the Czech Republic and randomized to either 5 days Oseltamivir followed by 5 days placebo, or 10 days Echinaforce Hotdrink. The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for non-inferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (two-sided) and using a confidence interval (CI) approach in the per protocol sample.
Recovery from illness was comparable in the two treatment groups at 1.5% vs. 4.1% after 1 day, 50.2% vs. 48.8% after 5 days and 90.1% vs. 84.8% after 10 days treatment with Echinaforce Hotdrink and Oseltamivir, respectively. Non-inferiority was demonstrated for each day and overall (95% CI [0.487 – 0.5265], generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce than with Oseltamivir (2.46% vs. 6.45%, p = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink.
Echinaforce Hotdrink is as effective as Oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self care.
Source : Current Therapeutic Research
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Prophylactic effect of herbal-marine compound (HESA-A) on influenza A virus infectivity
Parvaneh Mehrbod12, Aini Ideris12*, Abdul Rahman Omar12 and Mohd Hair-Bejo12
1. Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang Selangor, Malaysia 2. Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Influenza virus is still a severe respiratory disease affecting human and other species. As conventional drugs are not recommended for long time because of side effects and drug resistance occurrence, traditional medication has been focused as alternative remedy. HESA-A is a natural compound from herbal-marine origin. Previous studies have reported the therapeutic properties of HESA-A on psoriasis vulgaris and different types of cancers and we also showed its anti-inflammatory effects against influenza A infection.
This study was designed to investigate the potential properties of HESA-A as prophylaxis or treatment. To investigate the prophylaxis or treatment activities of HESA-A, Madin-Darby Canine Kidney (MDCK) cells were exposed to HESA-A and influenza A virus in different manners of exposure and different time intervals. The results were evaluated by MTT and HA assays.
It was found that HESA-A is much more effective against influenza cytopathic effects when it is applied for prophylaxis and also in concurrent treatment (p ≤ 0.05) but not in post-infection treatment (p ≥ 0.05).
In conclusion, HESA-A is significantly effective against influenza replication in prophylaxis application affecting the virus penetration/adsorption to the cell without any toxic effect on the cell viability.
Source : BMC Evidence Based Complementary and Alternative Medicine
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The Effectiveness and Mechanism of Toona sinensis Extract Inhibit Attachment of Pandemic Influenza A (H1N1) Virus
Huey-Ling You,1 Chung-Jen Chen,2 Hock-Liew Eng,3 Pei-Lin Liao,4 and Sheng-Teng Huang4,5
1Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
2Division of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
3Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
4Department of Chinese Medicine and Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
5Department of Chinese Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine,
TSL-1 is a fraction of the aqueous extract from the tender leaf of Toona sinensis Roem, a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus.
Source : Evidence Based Complementary and Alternative Medicine
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A commonly used Chinese herb for cold and fever contains ingredients that can fight influenza viruses, a study in China suggests.
Elsholtzia rugulosa (野拔子 ye ba zi), a common Chinese herb, is widely used in the treatment of cold and fever. A group of researchers of the Chinese Academy of Medical Sciences and Peking Union Medical College, as well as University of Macau investigated the anti-flu functions of the ingredients of this plant.
In order to elucidate the action mechanism and the active principles from the plant against anti-influenza virus, the influenza virus neuraminidase (NA) activity assay and in vitro antiviral activity assay were established, and the isolation of the active principles was guided by NA activity.
Their study established that five active constituents were found in ye ba zi and they are all flavonoids.
What are flavonoids? Flavonoids (or bioflavonoids) are a class of plant secondary metabolites fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as “nature’s biological response modifiers” because of strong experimental evidence of their inherent ability to modify the body’s reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory, anti-microbial and anti-cancer activity.
Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins.
The five constituents are:
- luteolin 3′-glucuronyl acid methyl ester
What is apigenin? Apigenin is described as a nonmutagenic bioflavonoid which is presented in leafy plants and vegetables (e.g., parsley, artichoke, basil, celery) and has significant chemopreventive activity against UV-radiation. Current research trials indicate that it may reduce DNA oxidative damage; inhibit the growth of human leukemia cells and induced these cells to differentiate; inhibit cancer cell signal transduction and induce apoptosis (cell death); act as an anti-inflammatory; and as an anti-spasmodic or spasmolytic.
Apigenin is also reported to be useful in fighting against antiestrogen-resistant breast cancer.
Apigenin is a bioflavone, considered to have a bioactive effect on human health as antioxidant, radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, immunity system modulater.
What is luteolin? Luteolin is a flavonoid thought to play an important role in the human body as an antioxidant, a free radical scavenger, an agent in the prevention of inflammation, a promoter of carbohydrate metabolism, and an immune system modulator. These characteristics of luteolin are also believed to play an important part in the prevention of cancer. Multiple research experiments describe luteolin as a biochemical agent that can dramatically reduce inflammation.
Luteolin inhibited the excess production of TNF-alpha, which directly causes inflammation and apoptosis. Luteolin also offers hope to develop a novel type of anti-inflammatory and anti-allergic drugs.
Luteolin is most often found in leaves, but it is also seen in rinds, barks, clover blossom and ragweed pollen. It has also been isolated from Salvia tomentosa. Dietary sources include celery, green pepper, perilla and camomile tea.
Source : Chinese Medicine News
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Eat This During Winter to Radically Reduce Your Risk of the Cold and Flu
Dr. Mercola has an indepth article on the healing powers of Mushrooms especially in regard to colds and flu.
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Randomized trial of vitamin D supplementation to prevent seasonal influenza A in school children
Mitsuyoshi Urashima,Takaaki Segawa, Minoru Okazaki, Mana Kurihara,Yasuyuki Wada, and Hiroyuki Ida
Background: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza.
Objective: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren.
Design: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D3 supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen.
Results: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D3 group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D3 compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006).
Conclusion: This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren.
Source : The American Journal of Clinical Nutrition
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Quercetin as Anti-Flu Support
Here is a question for you. What do grapevine leaves do when they come under attack from a viral infection? Answer: make more quercetin for their natural defense. There is no question that quercetin is active against many viral infections including the flu.
I first reported on quercetin’s flu-fighting ability in a 2008 posting, Quercetin Reduces Flu Susceptibility, which was an animal study showing that quercetin could reduce flu when animals were intentionally exposed. I followed this with an extensive review article last year, Quercetin: A Rising Star for Nerves, Immunity, and Metabolism. In this article I detail a number of studies showing that quercetin interferes with viral replication in a number of viruses including the flu.
Another newer animal study has found that quercetin inhibits both influenza A and B viruses and viruses were not able to develop resistance to quercetin treatment. When quercetin was used with anti-viral drugs then the anti-viral effect was even stronger and the quercetin prevented the development of resistance to the drugs which otherwise occurs. Studies like this support the synergistic combination of medical care with quercetin.
If a person should get the flu the severity of any infection is based on the ability of the flu virus to overwhelm the natural defense system of the human body, causing a state of inflammatory and toxic overload concurrent with exhaustion of the antioxidant defense system. Various antioxidant nutrients are also known to have anti-viral properties, including quercetin, NAC, resveratrol, vitamin C, and green tea. Scientists reviewing the science on this topic concluded, “The combination of antioxidants with antiviral drugs synergistically reduces the lethal effects of influenza virus infections. These results suggest that an agent [nutrient] with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with severe influenza-associated complications.”
The data is showing that quercetin, as well as a number of other synergistic antioxidants, make common sense during the cold and flu season and to lend a hand any time you are fighting a bug. Nutrients do not replace good medical care in case of the flu; they act synergistically to enhance it.
Source : Wellness Resources (Byron J Richards)
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N-acetylcysteine (NAC) Improves Immunity Against the Flu
"NAC has long been known as a flu-fighting nutrient based on a 1997 study of 262 older adults who participated in a double-blind randomized placebo-controlled study over a six-month period, some taking 600 mg of NAC twice daily or the others placebo. Individuals taking NAC were much less likely to have clinical influenza illness (29 percent of the NAC group compared to 51 percent of the placebo group. Flu that did occur in the NAC group was much less severe. Tests showed that cell-mediated immunity continually improved with NAC supplementation whereas it remained unchanged in the placebo group.
Source - Wellness News
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Vitamin D is Needed to Fight and Prevent the Flu
Byron Richards on Wellness Resources website discusses the study "Vitamin D controls T cell antigen receptor signaling and activation of human T cells" and states "The scientific fact that vitamin D is required for healthy immune system function is not new. There already exists an overwhelming body of information that vitamin D adequacy is essential for mounting a proper immune defense, preventing autoimmune disease, and preventing many cancers. The latest study shows that a lack of vitamin D causes the higher-powered T cells of your adaptive immunity to be unable to activate. The bottom line of the study is that a lack of vitamin D to your T cells is like having a dead battery in your car."
Source : Wellness News
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Vitamin D Deficiency is Why You Get Flu!
Dr Mercola's also discusses the study "Vitamin D controls T cell antigen receptor signaling and activation of human T cells." - "When a T cell is exposed to a foreign pathogen, it extends a signaling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D.
This means the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won't even begin to mobilize."
Dr. Mercola explains the protective effects of Vit D against Flu and also other diseases
Source : Dr. Mercola
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