Below is a summary of the scientific literature on each ingredient in the Invictimune formula.
Andrographolide is a major bioactive constituent of Andrographis paniculate, a traditional plant which has commonly been used for immune support.* Andrographolide sulfonate is the main ingredient in a well-known modern Chinese preparation (Ma et al., 2019).* Clinical evidence has suggested that this preparation provided significant immune support for elderly test participants (Huang et al., 2019b).*
Several peer-reviewed reviews have summarised evidence regarding andrographolide’s potential in supporting immune function (Jayakumar et al., 2013, Varma et al., 2011).*
Research suggest that andrographolide may be effective for supporting the immune system’s defences (Mishra et al., 2009b, Xu et al., 2006, Zaidan et al., 2005, Mishra et al., 2009a, Reddy et al., 2005, Tang et al., 2012, Wiart et al., 2005).*
A systematic review of randomized-controlled trials concluded that Andrographis paniculate extract may help to support respiratory health (Poolsup et al., 2004).*
Andrographolide is also said to be an antioxidant.* It has been shown to significantly reduce the accumulation of reactive oxygen species in a rat model (Shen et al., 2000).* In another study, andrographolide showed free radical-scavenging ability (Lin et al., 2009).* These effects could be mediated by supporting several immune system processes (Chiou et al., 2000).*
In an animal model of joint health, it has been found that andrographolide may help to maintain healthy chemokine levels (Luo et al., 2020).* Luo et al. (2020) also found it supported lipid peroxidation and helped to enhance antioxidant enzyme activity.*
Astragalus is said to have been used for thousands of years in Asia (Auyeung et al., 2016). The active part of the plant is said to be its 4-7 years old dried root (Auyeung et al., 2016). The major active components of Astragalus are polysaccharides, flavonoids and saponins (Auyeung et al., 2016).*
Astragalus may have immunosupportive effects, due to its polysaccharide component (Zheng et al., 2020).* It has been suggested that the polysaccharides in Astragalus may help to regulate immune function in multifaceted actions.* Specifically, the polysaccharides were found to support cytokines and antibody production via the conduction of signalling of immune cell activation, as well as supporting the balance of immune cells and therefore immune organ index (Zheng et al., 2020, Yin et al., 2012).* A 2019 clinical study found that Astragalus polysaccharides may help to maintain healthy expression of major cytokines (Huang et al., 2019a).*
Astragalus extract with its all components; polysaccharides, flavonoids, and saponins, has used in many supplements for a wide spectrum of purposes (Du et al., 2008).* Myriad evidence has highlighted its potential immunomodulatory and anti-oxidative effects (Du et al., 2008).* Various in vitro and in vivo studies have shown that astragalus may have non organ-specific tissue supportive effects by supporting a variety of signalling pathways and immune cells (Du et al., 2008). Qin et al. (2012) found that it supported healthy cytokine production and down-regulated signalling pathways in rats.* It has been suggested that astragalus may help to support a healthy liver (Huang et al., 2019a).*
The dried roots of Chinese skullcap, Scutellaria baicalensis, are said to have been used in China for over 2000 years for immune support (Wang et al., 2018).*
It is speculated that Chinese Skullcap has multiple functions due to its polysaccharide, flavonoids and flavonoids glycosides content (Wang et al., 2018).* These constituents may support the balance of immune system functions (Wang et al., 2018).
Chinese skullcap is perhaps best known for its purported broad spectrum immune support (Blach-Olszewska et al., 2008).* A study using human peripheral blood revealed that baicalin and wogonin-containing skullcap extracts may help to support the modulation of cytokine production (Blach-Olszewska et al., 2008).*
A number of other studies suggest that baicalin may be beneficial for supporting the immune system (Ding et al., 2014, Zhu et al., 2015, Moghaddam et al., 2014, Zandi et al., 2012, Li et al., 2015a, Johari et al., 2012, Shi et al., 2016, Tsao et al., 1982, Qiu et al., 2012).* Baicalin may help to support immune system defence mechanisms (Ding et al., 2014, Nayak et al., 2014, Zhu et al., 2015).* Baicalin has also been utilized for liver support (Wang et al., 2018).*
Another component of Chinese skullcap, viscidulin, may help to support cytokine communication (Fu et al., 2008).*
Skullcap is said to be an antioxidant which may potentially help to support against cell death caused by scavenging reactive oxygen species (Shao et al., 1999). Similarly, antioxidative effects may be beneficial for skin health (Gabrielska et al., 1997) and may potentially support brain health (Gao et al., 1999).*
Chan et al. (2010) compared the antioxidant capacity of Chinese skullcap to roots with polygonaceae, ginseng and araliaceae and found that water extracts of Chinese skullcap had the highest antioxidative capacity.* In addition, there is some evidence that baicalin could potentially be beneficial for maintaining healthy blood sugar levels (Li et al., 2012).*
Chinese skullcap may also support the regulation of nitric oxide, cytokines, chemokines and growth factors (Hong et al., 2013, Kim et al., 2009, Kim et al., 2018).* In several models, Chinese skullcap was suggested to be effective for joint support, as well as for liver support and vascular support (Cheng et al., 2017, Wang et al., 2017, Yang et al., 2013).*
Chinese skullcap was reported to help support neuronal cells subject to oxidative stress (Gong and Sucher, 1999, Kim et al., 2001).* Chinese skullcap was also found to support healthy memory in some animal models (Cao et al., 2016, Li et al., 2016, Yang et al., 2014).*
In addition, skullcap extracts were found to support neuronal health in an animal model (Heo et al., 2009).* The major components baicalin and wogonin were suggested to potentially be beneficial for supporting memory and a healthy nervous system (Cheng et al., 2008, Cho and Lee, 2004, Choi et al., 2010, Li et al., 2005, Mu et al., 2009, Tarrago et al., 2008).*
Chinese skullcap has also been used for liver support (Shimizu, 2000, Llovet and Bruix, 2003, Lv et al., 2006, Nan et al., 2002).* Some studies have suggested that baicalin may be the constituent which affords support to the liver (Hwang et al., 2005, Nan et al., 2002, Thanh et al., 2015, Wang et al., 2016).*
Forsythia is a Chinese herb which is said to have been used to help promote good immune health, skin health and respiratory health (Franzblau and Cross, 1986, Lin et al., 2013, Chen et al., 2015, Chen et al., 2016).
Some in vitro and in vivo studies suggest that Forsythia may help the body to maintain cellular health (Kim et al., 2003, Lee et al., 2010).* It has also been claimed that it may support the inhibition of mediators such as nitric oxide and cytokines (Kang et al., 2008, Kim et al., 2006, Lee et al., 2010, Lee et al., 2011, Kang et al., 2008, Ko et al., 2006).*
Some studies suggest that Forsythia has demonstrated potential for helping to support a healthy immune system (Guo et al., 2016, Wong et al., 2010, Liu et al., 2005).*
Extracts of Forsythia were said to have shown potential for supporting immune system defences (Deng et al., 2016, Ko et al., 2006, Li et al., 2012, Li et al., 2014, Li et al., 2011, Qu et al., 2016, Su et al., 2010, Yang et al., 2015, Zhang et al., 2002, Zhang et al., 2017).
Forsythia extract contains components which appear to have antioxidant qualities, including forsythoside A, isoforsythoside A, phillygenin, phillyrin, forsythialan A and polysaccharides (Kuang et al., 2011, Lu et al., 2010, Piao et al., 2009, Qu et al., 2012, Xia et al., 2015).*
Japanese honeysuckle, Lonicera japonica, is a plant native to eastern Asia. It is said to have long been used in China. It’s main purported efficacies relate to supporting a healthy immune response [reviewed by (Ma et al., 2019)].*
The polysaccharides present in the Lonicera japonica extract were found to help support the immune system in some mouse studies (Zhou et al., 2018, Kim et al., 2015).* In a different model, Lonicera japonica extract seemed to help support the regulation of cytokine production (Kwon et al., 2015). These studies may suggest that Japanese honeysuckle could be helpful for supporting modulation of the immune system, but further human research is needed.*
In other preliminary studies, Japanese honeysuckle is said to have shown potential for supporting immune system defences (Li et al., 2015b, Minami et al., 2019, Liu and Wang, 2011, Pan et al., 2006, Shi and Guo, 2010, Cheng et al., 2012, Zhang et al., 2010, Hu et al., 2010, Yu et al., 2008, Kashiwada et al., 2013, Chen et al., 2009).*
It has been said that honeysuckle appears to contain numerous antioxidant components (Li et al., 2015b).* In addition, some studies suggest that honeysuckle extract may help to maintain the intrinsic antioxidant enzyme system, which inhibits lipid peroxidation and maintains defence against oxidative damage (Gong et al., 2009, Li et al., 2015b).*
Quercetin is known as a polyphenol derived from fruits and vegetables (Davis et al., 2009). It has unique properties that may help to maintain immune system health (Davis et al., 2009).*
Quercetin has been shown to support healthy cytokine secretion, antioxidant activity and brain health in animal models (Dong et al., 2014, Jung et al., 2012, Liu et al., 2012, Kobori et al., 2016, Mlcek et al., 2016).*
In human studies, the effect of supplementing quercetin is less clear. Some studies have suggested it may be beneficial for the immune system (Nieman et al., 2007, Nieman et al., 2010) whereas other studies report no benefits to immune function (Nieman et al., 2009).* However, in the latter study there was no challenge to the immune system. This may suggest that quercetin’s beneficial role in supporting the body’s natural responses could potentially vary depending on the circumstances.* Notably, in a randomized controlled trial, quercetin supplementation had no significant influence on respiratory health.* However, in a subgroup of participants aged over 40, quercetin supplementation resulted in significant results (Heinz et al., 2010).* This may suggest that the effect of quercetin in humans may perhaps vary, depending on age and health status.*
Selenium is said to be an essential micronutrient as well as an antioxidant that plays important roles in immune system health (Avery and Hoffmann, 2018).* Adequate levels of selenium are said to be important for supporting various stages of immune response (Avery and Hoffmann, 2018, Hoffmann and Berry, 2008, Huang et al., 2012)*. Selenium deficiency has long been recognized to apparently affect immune cell function and lead to increased oxidative stress (Avery and Hoffmann, 2018, Hoffmann and Berry, 2008, Huang et al., 2012).* Beck et al. (2001) suggested that there may have been an association between selenium deficiency and unhealthy lungs in a mouse study.*
Inside the body, selenium is thought to be incorporated into selenoproteins, which are thought to be involved in the activation, proliferation and differentiation of numerous immune cells [reviewed by: (Huang et al., 2012)].*
Within immune cells, selenoproteins are thought to perform antioxidant, protein folding, cell signalling and other functions [reviewed by: (Huang et al., 2012)].* Notably, selenium levels may influence the production of reactive oxygen species [reviewed by: (Huang et al., 2012)].* Some evidence suggests that selenium supplementation may help to support immune system modulation (Beck et al., 2001, Broome et al., 2004).*
Elderberry is said to have long been used as supportive supplement for the immune system (Roxas and Jurenka, 2007).* It may help to maintain the body’s innate immunomodulatory effects by supporting the regulation of cytokines and adhesion molecules (Badescu et al., 2015).* Research has also reported that it has antioxidant properties and may also help to support healthy blood sugar levels (Netzel et al., 2005).* In addition, elderberries may contain a variety of vitamins, minerals and phytochemicals such as carotenoids (Roxas and Jurenka, 2007).* These nutritional constituents may make elderberry a versatile supplement for not only the immune system but also overall wellbeing (Roxas and Jurenka, 2007).*
A meta-analysis on elderberries found that flavonoids from elderberry extract may help to maintain immune defences (Ulbricht et al., 2014, Roschek et al., 2009).* Other possible constituents including anthocyanins and procyanidins may help to support the regulation of nitric oxide production (Ho et al., 2017).*
Notably, several trials have suggested that elderberry extracts may have immunosupportive effects in humans (Vlachojannis et al., 2010, Kong, 2009, Raus et al., 2015).* Lastly, a randomized controlled trial suggested that supplementing with Elderberry extract helped to support immune health in air travellers (Tiralongo et al., 2016).*
In summary, numerous studies suggest the potential efficacy of elderberry extract as a viable supplement for supporting the immune system during seasonal changes.*
Vitamin C is said to be an essential micronutrient which cannot be synthesized or stored by the human body.* Therefore, daily intake of Vitamin C is said to be critical (Carr and Maggini, 2017).*
As a cofactor for a battery of gene regulatory enzymes, Vitamin C has multifaceted functions ranging from epithelial barrier support to free radical scavenging (Carr and Maggini, 2017).*
Vitamin C is well documented to be an apparently effective micronutrient for supporting the immune system (Carr and Maggini, 2017).* In a systematic review of Vitamin C and Immune Function, the authors concluded that dietary vitamin C intake should "provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels," (Carr and Maggini, 2017).*
Vitamin D is a fat-soluble micronutrient which is said to be critical for survival (Nair and Maseeh, 2012).* Vitamin D is typically thought to be obtained from sunlight, but it may also be found in foods such as fish, eggs and dairy (Nair and Maseeh, 2012).* Our bodies may synthesise vitamin D from cholesterol, given exposure to adequate UV rays (Nair and Maseeh, 2012).* There is only sufficient UV rays from the sun to synthesise vitamin D when the UV index is at least 3 (Nair and Maseeh, 2012).*
The potential benefits of Vitamin D may include immune health (Aranow, 2011, Daneshkhah et al., 2020, Ebadi and Montano-Loza, 2020, Grant et al., 2020, Ilie et al., 2020, Lanham-New et al., 2020, McCartney and Byrne, 2020), cognitive support (Lee et al., 2020, Soni et al., 2012), bone health (Bischoff-Ferrari et al., 2009) and possibly emotional wellbeing (Anglin et al., 2013, Eyles et al., 2005, Shaffer et al., 2014, Spedding, 2014).* Some evidence suggests that adequate vitamin D may also play a role in helping to maintain healthy blood sugar levels (Hu et al., 2019).*
Researchers from Trinity College in Dublin recently speculated that vitamin D may potentially have immunosupportive properties, through supporting the modulation of both the adaptive and innate immune system, through cytokines and regulation of cell signalling pathways (Laird et al., 2020).* Surprisingly, the researchers found that lower latitude and typically ‘sunny’ European countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency (Laird et al., 2020).* The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean vitamin D concentrations, lower levels of deficiency and for Norway and Finland, better health outcomes (Laird et al., 2020).* The researchers suggested that this may be attributable to higher rates of vitamin D supplementation and fortification of foods in these Nordic countries (Laird et al., 2020).*
Vitamin E is said to function as a potent antioxidant and is thought to be obtained exclusively from the diet (Rizvi et al., 2014).* It has been suggested that vitamin E may help to support cell membranes (Rizvi et al., 2014).* Recent commentators have suggested that the current dietary guidelines for vitamin E could possibly be inadequate (Wu et al., 2018).*
Notably, immune cells usually contain higher levels of vitamin E due to higher demand (Lee and Han, 2018).* Immunomodulatory effects of vitamin E has been reportedly shown in preliminary animal and human studies under various test conditions (Lee and Han, 2018).*
In addition, research indicates that vitamin E may help to support a number of cell-mediated immune responses (Lee and Han, 2018).* These may potentially include supporting the proliferation of white blood cells, antibody levels, immunoglobulin levels, interleukin (IL)-2 production and natural killer cell activity (Lee and Han, 2018).* In an animal study, Vitamin E was found to seemingly support T helper 1 cytokine production (Han et al., 2000).*
In addition, some populational studies have found an association between higher vitamin E intake and good heart health, but further research is needed (Knekt et al., 1994, Stampfer et al., 1993). It has been suggested that Vitamin E may also help maintain healthy arteries, but again, more research is needed (Min et al., 2018, Shen et al., 2018).*
Zinc is said to be an essential mineral involved in regulating intracellular signalling pathways in innate and adaptive immune functions (Wessels et al., 2017).* It has been suggested that adequate zinc may be needed so as to be transiently transferred from serum into the organs, possibly acting as a signal for immune cells (Wessels and Cousins, 2015).* In addition, it has been suggested that intracellular defence, cytokine production and immune cell maturation may be dependent on adequate zinc (Wessels and Cousins, 2015).* It has also been suggested that adequate zinc may help to support lymphocyte functions (Wessels et al., 2017).*
According to Haase et al. (2006), zinc deficiency may potentially affect roughly 30% of the elderly population.* Some studies have associated zinc deficiency with poor health status (Kozlowski et al., 2012, Bonaventura et al., 2015, Chabosseau and Rutter, 2016).*
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