Some viruses, such as the current one we are all dealing with, are known to inhibit the induction of interferon and interferon signaling pathways (Interferons are immune-stimulating compounds that suppress viral attacks.) The name interferon is derived from the interference it provides with respect to a virus’s ability to infect or replicate. This permits the virus to attack the body while the appropriate immune responses are thwarted. Inappropriate immune responses can lead to an inflammatory “cytokine storm” that causes serious cell damage. My husband, Don Bellgrau, Professor of Immunology, authored a paper on the cytokine storm and interferon, recently accepted by the Scandinavian Journal of Immunology1. In dealing with a virus, instead of “boosting the immune system”, it makes sense that one would want to target the specific arm of the immune system that is involved with the viral activity, namely interferons.
OAS-1 is one of many interferon-inducible genes. Dr. Bellgrau explains OAS-1 as a gene that impairs the ability of viral RNA to replicate, however, gene variants may affect the activity of this gene. It is known that some people have genetic variants and may produce low OAS-1 protein and may face the scenario of poor antiviral defense. There is rich scientific literature that indicates this is one reason why some people are more susceptible to damage caused by certain viruses. (More on genetic associations after the discussion of viral support for interferon.) In Sept. 2020, a pre-published report came out entitled “Nutraceuticals have potential for boosting the type 1 interferon response...” 2
"Only 25% of the virus-infected subjects in the NAC group developed symptoms, as contrasted to 79% of those in the placebo group."
Nutraceuticals for Viral Support
The authors of the article note that in light of recent events, “it is fortuitous that recent discoveries point the way to effective nutraceutical measures for potentiating the type 1 interferon response to RNA viruses.”
As we discuss nutritional viral support, specifically interferon support, think of the analogy of the car struggling to make it up the hill because the engine was not tuned - there are no claims here for fixing a sputtering engine, only for tuning it to be prepared for the challenge!
The first nutraceutical approach mentioned in this article is antioxidants, because the specific oxidation of the Cys98 residue on the protein domains of TLR7 blocks the signal for interferon production. TKR7 is a toll-like receptor, and TLR7 provides a key stimulus to type-1interferon induction by RNA viruses. The nutritional antioxidants recommended by the article, for being effective interferon support for this pathway, are alpha lipoic acid, N-acetyl cysteine, and elderberry. Alpha lipoic acid is a potent free radical scavenger, N-acetyl cysteine (or NAC) raises glutathione levels (glutathione is a major antioxidant), and elderberry is very high in anthocyanins (highly concentrated antioxidant phytochemicals).
Since antioxidants function in many different pathways, the authors suggest that the impact of these antioxidant nutraceuticals might also be expected to favor homeostasis in lung tissue, rather than an excessive inflammatory reaction.
The article further discusses another pathway, and notes that nutraceuticals - such as ferulic acid (found in high concentration in elderberry), alpha lipoic acid, or sulforaphane - “are known to promote induction of HO-1 (heme-oxygenase), and hence may have some utility for boosting type 1 interferon response.”
Spirulina was another focus nutrient of the article. Spirulina exhibits NAPDH oxidase inhibiting activity, and “This phenomenon likely explains many of the profound antioxidant and anti-inflammatory effects observed when spirulina is administered. Hence, ingestion of spirulina may have the potential for boosting type 1 interferon response in the context of RNA virus infection.”
It was previously mentioned that the oxidation of Cys98 blocks the signal for interferon production. The article names N-acetyl cysteine (NAC) for promoting the synthesis of glutathione, a cofactor for certain peroxidases and a catalyst in reactions that reconvert oxidized cysteine groups to their native form.
The article cites a little-noticed 6-month controlled clinical study enrolling 262 primarily elderly subjects, those receiving 600 mg NAC twice daily, as opposed to those receiving placebo, experienced significantly fewer influenza-like episodes and days of bed confinement.3
Only 25% of the virus-infected subjects in the NAC group developed symptoms, as contrasted to 79% of those in the placebo group. “Given the carnage that influenza wreaks among the elderly, it is most regrettable that no effort has been made to replicate this study, conducted over 20 years ago. The particular utility of NAC in the elderly might reflect the fact that plasma cysteine levels and cellular GSH levels tend to decline with advancing age” (McCarty, MF & DiNicolantonio, JJ. 2020.)
MAVS (mitochondrial antiviral signaling proteins) are key mediators of the interferon response. Measures that suppress or amplify the cellular pool of UDPN-acetylglucosamine - correspondingly suppress or amplify the activation of MAVS, and glucosamine is the nutrient in this case that amplifies the pool of UDPN-acetylglucosamine. Feeding mice a glucosamine enriched diet (2.5% by weight) markedly enhances the survival of wild-type mice that have the influenza virus. The article does note that glucosamine is inefficiently absorbed after oral administration. It is much more effective to provide building blocks and synergy for glucosamine administration, such as N-acetyl glucosamine, green-lipped mussel, milk thistle, silymarin, cysteine, and taurine, to name a few.
Since selenium is an essential cofactor for certain peroxidases (which can induce interferon), and selenium deficiency has been endemic in certain regions of China and other parts of the world, insuring adequacy of selenium nutrition might also be appropriate in this context.
Not surprisingly, influenza is more pathogenic in selenium-deficient mice, and selenium deficiency also increases the rate at which viruses can mutate, promoting the evolution of strains that are more pathogenic and capable of evading immune surveillance. Selenium also made the list of top nutraceuticals in the article.
The article's authors conclude by stating that the administration of spirulina, ferulic acid (elderberry), alpha lipoic acid, sulforaphane, N-acetylcysteine, selenium, and glucosamine ... might be expected to support RNA virus attack by amplifying the signaling functions of TLR7 and MAVS in evoking type 1 interferon production. They also include beta glucans - which can amplify dendritic cell activation, as it has clinically documented immunostimulant effects and has shown to support mice challenged with influenza. Additionally, zinc is included in the list, because “zinc supports the effective function and proliferation of various immune cells.”
"Influenza is more pathogenic in selenium-deficient mice, and selenium deficiency also increases the rate at which viruses can mutate..."
Genetic Associations
Back to the genetic influences that were alluded to earlier: The A/G and G/G SNP genotypes of rsl0774671 and rs2660 (from the previously mentioned OAS1 SNP) may be beneficial for the activity of 0AS1. Having at least one G allele is linked to higher activity, with G/A linked to intermediate activity, and A/A linked to lowest and possibly impaired activity.4
As a general disclaimer on DNA reporting, keep in mind that these DNA reports are based on association studies, which are correlative and are not necessarily causative. In addition, any one genetic variant will typically contribute only a portion to the overall health scenario, and non-genetic factors play a large role in the overall health scenario as well.
The discussion of SNPS (single nucleotide polymorphisms), or genetic variants, and genotypes (ie A/G, GG, etc) is beyond the scope of this article, however, the NIH has a Genetic Home Reference Guide with much information that can be found in an internet search. Again, it makes sense, nutritionally speaking, that we would want to support the immune system specifically with nutrition that is known for targeting interferon and interferon signaling pathways, especially since some may not effectively express their 0AS1 gene. That would include support with all of the nutrients listed above for interferon support. Having said that, keep in mind that a genetic variant will typically contribute only a portion to the overall health scenario, and non-genetic factors play a large role in the overall health scenario as well. Therefore, having one or more of these genotypes does not necessarily describe a phenotype. Both 23andme and AncestryDNA provide this information in their raw data, which then can be analyzed after utilizing one of the several program options out there that crunch the raw data into an understandable report.
Dr. Lynn Toohey received her Ph.D. in nutrition (summa cum laude) from CO State University in Ft. Collins, CO. She has lectured to chiropractors, chiropractic associations, and other health professionals across the country and overseas on nutrition-related topics, and has published numerous articles in peer-reviewed journals. You may contact Dr. Toohey at [email protected].
References:
1. Bellgrau D. and Modiano J.The cytokine storm—An appropriate, over-reactive response to SARS-CoV-2 or the wrong immune pathway? Epub Sept. 2020.
2. McCarty, MF & DiNicolantonio, JJ Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses, including influenza and coronavirus (Progress in CD 63 (2020) 383-385.
3. De FS, Grassi C, Carati F. Attenuation of influenzalike symptomatology and improvement of cell-mediated immunity with long-term N-acetyl cysteine treatment. Eur Respir J1997 July;10(7):1535-1541.
4. Jing, H. Association of SARS susceptibility with single nucleic acid polymorphisms of 0AS1 and MxA genes: a case-control study. BMC Infectious Disease. 6, 106 (2006); Zhao Y, Kang H, Ji Y, Chen X. Evaluate the relationship between polymorphisms of 0AS1 gene and susceptibility to chronic hepatitis C with high resolution melting analysis. Clin Exp Med. 2013;13(3):171-176; Juno J, Fowke KR, Key nan Y. Immunogenetic factors associated with severe respiratory illness caused by zoonotic H1N1 and H5N1 influenza viruses. Clin Dev Immunol. 2012;2012:797180.
