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Featuring Quercetin, NAC, Zinc, EGCG & Vitamin C
Immune Active provides high potency vitamin C and zinc and features quercetin, NAC and EGCG to help support a healthy immune response and promote antioxidant processes.
While Immune Active has been designed to be safe when with comorbidities, please always check with your healthcare practitioner before starting any new supplement.
This product is useful in the following phases of COVID:
Immune Active is useful and safe to use in all The 4 Phases of COVID. It has also been designed to be taken by people with comorbidities but always check with your doctor before starting any new supplement, especially if you have a comorbidity or are on medication.
Prevention Phase: Support is focused on immune surveillance efficiency and reduction of baseline levels of inflammation, to improve outcomes if the patient becomes infected,
Infection Phase: Support emphasizes immune activity against infection,
Escalating Inflammation Phase:- support is focused on anti-inflammatory measures.
Recovery Phase: Support is focused on resolving inflammation, inhibiting fibrosis and other forms of tissue damage, curtailing losses of function, and restoring and reoptimizing function. People have been observed to relapse into the Escalating Inflammation Phase, so it is essential for clinical surveillance to continue well into what may appear to be the Recovery Phase.
Immune Active and ImmuCore® (Ultra Potent-C + medicinal mushrooms) also complement each other. While Immune Active is safe through The 4 Phases of COVID, ImmuCore® should only be taken in the Prevention and Infection Phase.
The COVID Inflammasome
By now, you've heard about the 'cytokine storm' in COVID, where the SarsCoV-2 virus causes large-scale inflammation in the body of certain people, which results in the lungs flooding with fluid, vital organs shutting down, and the possibility of death.
The starting point for the cytokine storm in the cell is the 'inflammasome'. There are different inflammasomes - the one involved in COVID is called NLRP3.
Imagine inflammasomes like flat-pack furniture. They can be assembled in just 10 minutes if your cells are damaged or detect danger.
Once assembled and activated, they trigger an inflammation cascade that, in some people, can be hard to stop and can overwhelm the body.
The good news is that new research shows that certain nutrients and botanicals can 'down-regulate' the NLRP3 inflammasome and make it less likely to 'overreact' when the body is exposed to the SarsCoV-2 virus. This means less chance of a cytokine storm.
What are some risks associated with the NLRP3 inflammasome?
NLRP3 inflammasome activity is responsible for pneumonia, sepsis and acute respiratory distress syndrome (ARDS) - as seen in COVID.
NLRP3 inflammasome activation has also been linked to diseases not usually associated with infections, such as Alzheimer’s, Type 2 diabetes, autoimmune diseases and atherosclerosis.
What are the bioactives that down-regulate the NLRP3 inflammasome?
Metagenics Immune Active contains almost all these bioactives in 1 pill! You'd just need to add Vitamin D3 (1000iu - 5000iu per day depending on your blood levels) and SPM's (SPM's are only for if you have COVID or trying to reduce existing inflammation).
This formulation makes it much easier to take these bioactives than trying to round up all the single versions and swallow lots of pills daily.
150 mg EGCG (as decaffeinated+ green tea leaf extract) per serving. EGCG is categorized as a flavonoid polyphenol, a compound typically found in plants. Polyphenols can help promote antioxidant processes in the body.
NAC (N-Acetyl Cysteine) is a metabolite of the sulphur-containing amino acid cysteine. NAC stimulates the biosynthesis of glutathione, a key antioxidant produced in the body. Glutathione plays an important role in protecting the body against oxidative stress and supporting healthy liver detoxification processes.
Quercetin is a polyphenolic flavonoid substance present in a variety of plant foods. Quercetin helps protect cells from harmful free radicals. Preclinical studies demonstrate that quercetin affects immunity by acting on leukocytes and other immune cells.
|Serving Size: 1 Capsule|
|Ingredients||Amount Per Serving|
|Vitamin C (as ascorbic acid)||200 mg|
|Zinc (as zinc glycinate)||30 mg|
|Decaffeinated†† Green Tea (Camellia sinensis) Leaf Extract [standardized to 60%||375 mg|
|(225 mg) catechins and 40% (150 mg) epigallocatechin gallate (EGCG)]|
- Capsule (hydroxypropylmethylcellulose), magnesium stearate (vegetable), and silica
- This product is non-GMO and gluten-free
- Take two (2) capsules daily or as directed by your healthcare practitioner.
- Read ingredients, dosages and cautions carefully.
- Do not exceed recommended dosages unless on the advice of a healthcare provider.
- If you are on medication, taking nutritional supplements, suffering from any medical condition, pregnant, or breastfeeding, consult your healthcare practitioner before starting any new food, supplement or remedy.
- Do not stop prescribed medication without consulting your healthcare practitioner.
- Report any new or strange symptoms to your healthcare practitioner to ensure appropriate medical care.
- Do not use this product if you are allergic to any of the ingredients.
- Due to the unique nature of each individual person’s health, specific results cannot be guaranteed and may vary from person to person.
- The product information provided is for educational purposes and is not intended as either diagnosis or treatment of any disease, nor does it replace professional medical advice.
- This medicine is not intended to diagnose, treat, cure of prevent any disease.
- Keep out of the reach of children.
- Store in a cool (below 25°c), dry place.
Read more about The Inflammasome here.
- Inflammasomes are the cellular machinery that drive inflammation.
- Inflammasome activation amplifies inflammation.
- Nutritional bioactives help regulate inflammasome activation.
What is an inflammasome?
- Inflammasomes are protein complexes, built by “ready-to-go” parts within a cell.1
- Internal and external danger signals, such as an infection and cellular damage, can trigger inflammasome assembly in as little as 10 minutes.1,2
- After activation, inflammasomes cause release of proinflammatory cytokines such as IL-1β and cascade to an orchestrated inflammatory cell death known as pyroptosis and downstream immune responses.1
- Several inflammasomes exist, and NLRP3 is considered the most clinically relevant inflammasome.3
Why do we have inflammasomes?
- Inflammasomes are part of the innate immune defenses and primarily function to keep infections from spreading.1
Are inflammasomes always helpful?
- Inflammasome activation and pyroptosis are highly inflammatory, and the response can backfire, especially if not well-regulated.1
- For example, NLRP3 inflammasome activity is responsible for acute respiratory distress syndrome (ARDS), seen secondary to pneumonia or sepsis.4
- Inflammasome activation has been linked to diseases not usually associated with infections, such as Alzheimer’s, type 2 diabetes, autoimmune diseases, and atherosclerosis.2
Nutritional bioactives that influence inflammasome activation:
- N-acetylcysteine (NAC)8-10
- Epigallocatechin-gallate (EGCG)7,13,14
- Vitamin C15,16
- Vitamin D17,18
- Specialized pro-resolving mediators (SPMs)19-24
Nutritional bioactives that modulate inflammasome activation
Nutritional bioactives are compounds found in the diet that have biological effects. Certain nutritional bioactives have been studied for their specific action in certain physiological conditions.
- Quercetin, a polyphenol found in many fruits and vegetables, has been shown to reduce the expression of NLRP3 inflammasome components and secretion of proinflammatory cytokines such as IL-1β.5
- Quercetin suppresses the NF-κB pathway that also leads to reduced activation of NLRP3 inflammasome and productions of proinflammatory cytokines.6
- Quercetin helps ameliorate mitochondrial dysfunction and endoplasmic reticulum stress, suppressing reactive oxygen species (ROS) formation in inflamed tissues.7
- NAC is a precursor in the production of glutathione, and supplementation can increase tissue glutathione levels in humans.8
- In an experimental model of ROS-triggered NLRP3 expression, treatment with NAC suppressed the activation of the inflammasome.9
- NAC regulates mRNA expression of lipopolysaccharide (LPS)-triggered NLRP3 inflammasome, lowering cytokines such as IL-1β.10
- Zinc is a vital nutrient for proper immune function. Zinc deficiency (especially common in older populations) in immune cells activates the NLRP3 inflammasome, induces IL-1β secretion, and contributes to inflammation.11
- Zinc inhibits NLRP3 by activating the Nrf2 antioxidant pathway and reduces the production of ROS.12
- EGCG, a polyphenol commonly found in green tea, suppresses NLRP3 inflammasome mRNA, activation, and oxidative stress, reducing IL-1β expression in inflamed cells.7,13
- EGCG activates Nrf2 antioxidant pathway, decreasing NLRP3 inflammasome activation.13
- EGCG also inhibits NF-κB activation and reduces expression of multiple inflammatory signals such as TNFα, IL-6, iNOS, and MMPs.14
- Preclinical evidence shows vitamin C and quercetin together act as antioxidants and block a critical triggering event of the NLRP3 inflammasome.15
- Vitamin C inhibits NLRP3 activation through scavenging mitochondrial ROS, rather than by inhibiting NF-κB.16
- Vitamin D has two unique pathways that regulate inflammasome activation.17
- Vitamin D signaling through vitamin D receptor (VDR) binding is one mechanism.17
- VDR can also directly bind to NLRP3 and prevent the inflammasome from assembling.17
- Defects in this mechanism may be involved in the development of allergic diseases, as inflammasome activation is involved in T helper type 2 responses.18
Specialized pro-resolving mediators (SPMs)
- SPMs, bioactives that can be found in specialized fractions of fish oil, promote inflammation resolution without causing immunosuppression.19
- Supplementing SPMs enhances pathogen phagocytosis in immune cells.20
- In an animal model SPM RvD2 blocks NLRP3 inflammasome activation, reduces IL-1β, and reprograms macrophages to a proresolving phenotype.21
- In mice with lung infections, SPMs RvD1 and RvE1 increase bacterial clearance and shorten the time to inflammation resolution.22,23
- SPM PD1 inhibits H1N1 and H5N1 influenza viral replication in human lung cells.24
A normal inflammatory response and activation of inflammasome protects the host from infection or prevents further tissue damage. However, prolonged dysregulated inflammasome activities have been associated with development of immune and metabolic disorders. Nutritional bioactives may provide a safer approach in addressing the harmful effects associated with dysregulated inflammation and inflammasome activation.
- Nrf2: nuclear factor erythroid 2-related factor 2 TNF-α: tumor necrosis factor alpha
- NF-kB: nuclear factor kappa beta
- iNOS: inducible nitric oxide synthase
- MMPs: matrix metalloproteinases
1. Schroder K et al. Cell. 2010;140(6):821-832.
2. Yang Y et al. Cell Death Dis. 2019;10(2):128.
3. Abderrazak A et al. Redox Biol. 2015;4:296-307.
4. Yuen KS et al. Cell Biosci. 2020;10:40.
5. Hu QH et al. Biochem Pharmacol. 2012;84(1):113-125.
6. Zhang QY et al. J Nutr Biochem. 2014;25(4):420-428.
7. Wu J et al. Eur J Pharmacol. 2014;745:59-68.
8. DiNicolantonio JJ et al. Open Heart. 2017;4(2):e000599.
9. Wang R et al. Lab Invest. 2017;97(8):922-934.
10. Liu Y et al. Innate Immun. 2015;21(6):587-597.
11. Summersgill H et al. Cell Death Dis. 2014;5:e1040.
12. Fan Y et al. Mol Med Rep. 2017;16(4):5195-5202.
13. Tsai PY et al. Free Radic Biol Med. 2011;51(3):744-754.
14. Shin HY et al. Int Arch Allergy Immunol. 2007;142(4):335-344. 15. Choe JY et al. Inflammation. 2017;40(3):980-994.
16. Sang X et al. Imnflammasome. 2016;2:13-19.
17. Rao Z et al. Front Immunol. 2019;10:2783.
18. Huang H et al. Clin Exp Immunol. 2018;194(1):17-26.
19. Serhan CN. FASEB J. 2017;31(4):1273-1288.
20. Souza PR et al. Circ Res. 2020;126(1):75-90.
21. Lopategi A et al. J Leukoc Biol. 2019;105(1):25-36.
22. Codagnone M et al. Mucosal Immunol. 2018;11(1):35-49. 23. Seki H et al. J Immunol. 2010;184(2):836-843.
24. Morita M et al. Cell. 2013;153(1):112-125.
- Vitamin C may increase the absorption of iron so it is not recommended if your body has a genetic iron storage issue such as haemochromatosis.
- Vitamin C may increase aluminum absorption from antacids
- Vitamin C may decrease exogenous estrogen metabolism
- Vitamin C may decrease fluphenazine concentrations
- Large doses of vitamin C may reduce half-life of HIV protease inhibitors
- Warfarin activity may be affected by Vitamin C - not recommended for use with Warfarin.
- If you are using medication to lower blood pressure or have a bleeding disorder, consult your healthcare professional before using vitamin C.
- Your body has no way to store this important mineral, so it is important to ensure you’re getting in reguarly through your diet or supplementation.
- Zinc’s main role is to help your body increase white blood cells and fight off infection. It also assists with the release of antibodies.
- Deficiency has been linked to increased instances of sickness so zinc is commonly used for the prevention and treatment of colds and flu.
- Look for supplements that combine the power of vitamin C and zinc.
- Suggested dose - normal: 15 to 30 mg per day.
- Suggested dose - COVID or viral prevention: 30-60mg
- Pregnant women should aim for 12 mg per day since it’s essential for normal fetal development.
How to incorporate
- If you’re eating a healthy well-rounded diet, you should be getting in the proper amount of zinc per day without needing a supplement.
- During winter and flu season, supplementstion might be needed to maintain slightly higher levels for a few months.
- If getting over a cold quickly is your goal, supplementing at least 75 mg per day can reduce cold duration and symptoms so you can get back to your life.
- Zinc may decrease absorption of some antibiotics when taken at same time
- Zinc may increase side effects of cisplatin
- Zinc may decrease the absorption of penicillamine
- Amiloride may increase amount of zinc in body
Zinc plays a crucial role in the function of essentially all immune cells. Deficiency of this critical element has a profound impact on immune response, increasing susceptibility to a variety of infections.208-212
One of zinc’s critical roles in immune function is its role in thymulin production and activity.213
In addition, zinc has specific and well-known antiviral properties.214
Increasing intracellular zinc concentrations in cell culture impairs the replication of a variety of RNA viruses including SARS-CoV-1. Intracellular zinc has been shown to inhibit RNA synthesis by suppressing the SARS-CoV-1 replication and transcription complex.215
In vivo evidence for zinc’s antiviral role comes from a Cochrane review that found zinc intake was associated with a significant reduction in the duration of the common cold. Many of the studies showing benefit when taken during the course of an infection were in the form of a zinc lozenge.216 It makes sense to utilize this mode of delivery during the acute infection phase.
Zinc has also been shown to suppress Th17 cell development.217
Interleukin-17 (IL-17) made by Th17 cells has been shown to drive an inflammatory feedback loop via IL-6 induction.218
Zinc dependent transcription factors are involved in the regulation of the gene expression of IL-6 and TNFα.219
The effect of SNPs in genes encoding zinc transporters on blood zinc levels in humans has been examined.220
Older individuals with gain of function IL-6 SNPs have been shown to have a greater need for zinc.221
Zinc supplement in older individuals with gain of function IL-6 SNPs and low zinc were shown to have lower IL-6 and MCP-1 levels upon zinc supplementation.222
Anosmia (loss of smell) and dysgeusia (distorted sense of taste) are commonly being reported in patients at every phase of COVID-19.223
These are also classic symptoms of zinc deficiency. It is too early in the discovery process to determine if this is cause or effect, nonetheless zinc deficiency greatly impairs immune function, especially resistance to viral infections. Notably, inadequate dietary consumption of zinc is found in almost half the older population.224
208. Shankar, AH, and Prasad, AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. 209. Haase, H, Rink L, Multiple impacts of zinc on immune function. Metallomics.
210. Haase, H, Rink L, Zinc Signals and immune function. Biofactors ((2014) Jan-
211. Dardenne, M. Zinc and immune function. Eur J Clin Nutri. 2002 Aug;56
212. Chasapis, CT, Loutsidou AC, Spiliopoulou, CA, Stefanidou, ME. Zinc and
human health: an update. Arch Toxicol. 2012 Apr;86(4):521-34.
213. Bach JF, Dardenne M. Thymulin, a Zinc-Dependent Hormone. Med Oncol
Tumor Pharmacother. 1989;6(1):25-9.
214. Krenn BM, Gaudernak E, Holzer B, Lanke K, Van Kuppeveld FJM, Seipelt J.
Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitol against Picornavirus Infections. Journal of Virology Dec 2008, 83 (1) 58-64; DOI: 10.1128/JVI.01543-08
215. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010 Nov 4;6(11):e1001176.
216. Zinc for the common cold. Cochrane Systematic Review (2013) 6. John Wiley and sons, Ltd
217. Kitabayashi C, Fukada T, Kanamoto M, Ohashi W, Hojyo S, Atsumi T, et al. Zinc suppresses Th17 development via inhibition of STAT3 activation. Int Immunol. 2010 May;22(5):375-86.
218. Ogura H, Murakami M, Okuyama Y, Tsuruoka M, Kitabayashi C, Kanamoto M, et al. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity. 2008 Oct 17;29(4):628-36.
219. Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Tesei S, Malavolta M. Nutrient-gene interaction in ageing and successful ageing. A single nutrient (zinc) and some target genes related to inflammatory/immune response. Mech. Ageing Dev. 127, 517–525.
220. Fujihara J, Yasuda T, Kimura-Kataoka K, Takinami Y, Nagao M, Takeshita H. Association of SNPs in genes encoding zinc transporters on blood zinc levels in humans. Leg Med (Tokyo). 2018 Jan;30:28-33.
221. Mocchegiani E, Romeo J, Malavolta M, Costarelli L, Giacconi R, Diaz LE, Marcos A. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr). 2013 Jun;35(3):839-60.
222. Mariani E, Neri S, Cattini L, Mocchegiani E, Malavolta M, Dedoussis GV, et al. Effect of Zinc Supplementation on Plasma IL-6 and MCP-1 Production and NK Cell Function in Healthy Elderly: Interactive Influence of +647 MT1a and -174 IL-6 Polymorphic Alleles. Exp Gerontol . 2008 May;43(5):462-71.
223. Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia: common findings in COVID-19 patients. Laryngoscope. 2020 Apr 1.
224. Pisano M, Hilas O. Zinc and Taste Disturbances in Older Adults: A Review of the Literature. Consult Pharm. 2016 May;31(5):267-70.