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Summary: The recent international health crises due to viral infections has made one thing very clear: We need a new strategy to combat viral infections. Ebola has been in the international news daily for the past two months, while the US has had a recent upsurge of measles, enterovirus D68, and a new polio-like paralytic disease thought to be due to a viral infection. The fact that these viral-infection health crises exist in these modern times is prima facie evidence of the failure of current systems and the need—not for new treatments within the same model — for a new model better suited for international distribution, disease prevention, and broad-spectrum effectiveness. The multifaceted model presented here gives us four areas upon which we can focus our efforts: 1) targeting the virus directly, 2) blocking viral replication, 3) supporting immune function, and 4) supporting cellular and whole-body health. These are illustrated in the accompanying diagram and briefly described and exemplified in the four respective paragraphs that follow. These interventions have proven effectiveness, low cost, and international availability without the costs and adverse effects of current medical treatments.
History and Perspectives
What we as doctors learn in medical school about viral infections is summarized within the following course titles: Microbiology, Pathology, and Pharmacology. Following this instruction, the treatments that we use are sanitation, vaccination, and antiviral drugs, respectively. Based on training and my experience with other doctors, I suggest here that most medically-trained doctors are — at least per their formal training — unable to see beyond these blinders and limited options. What I would like to do in this article is broaden those conceptual and therapeutic horizons via a structured antiviral strategy that includes the previously mentioned sanitation, vaccination and antiviral drugs but extends beyond these limited options. Additional citations, support, and clinical details (e.g., dosing and contraindications) for this strategy are available in a digital format constantly updated; the purpose of this article is to structure the strategy, to shift the paradigm.
The fact that most doctors learn nothing about the science of Nutrition in medical school is well known publicly and within medical school academics. Typically, most medical students read one chapter about pathologies caused by extreme nutritional deficiencies, but they learn essentially nothing about therapeutic nutrition and how it can be applied in the prevention and treatment of disease. Does ignoring Nutrition force doctors by default to over-rely on drugs and surgery? Would not public health be better served if information were distributed on the nutritional prevention of viral infections, so that patients and doctors alike would have more options?
What I have noticed through the various doctorate programs I have attended is that clinical training in the management of viral infections remains mostly phenomenalistic and enigmatic, rather than deciphered and structured. As an educator, researcher and writer, I have learned through experience to structure information in such a way that the accessibility and retention of the information is enhanced by students/readers (e.g. the DIRT, MYBESTPLAIDFIG for nutritional immunomodulation, and FINDSEX® acronyms). My main purpose in writing this essay is to demonstrate a unique and structured antiviral strategy and to provide representative examples of its practical application.
Rather than viewing viral infections in a manner that is phenomenalistic and enigmatic, and therefore unwieldy, leading to clumsy prevention and treatment strategies, we should deconstruct the complexity of the infectious process. Doing so – at least in the manner that I have described – gives us four areas upon which we can focus our efforts: 1) targeting the virus directly, 2) blocking viral replication, 3) supporting immune function, and 4) supporting cellular and whole-body health. These are illustrated in the accompanying diagram and briefly described and exemplified in the four respective paragraphs that follow.
Image copyright © 2014 Vasquez A. Antiviral Nutrition. International College of Human Nutrition and Functional Medicine, 2014. https://www.amazon.com/dp/B00OPDQG4W
Multicomponent Antiviral Strategy
1. Targeting the virus directly: Targeting the virus directly has been the focus of medical practice and public health efforts through sanitation, vaccination, and – more recently – the use of disease-specific antiviral drugs. Several nutrients and botanicals are also very effective for directly targeting viral infections, and I will provide two examples here. The mineral selenium has a wide margin of safety and provides antiviral benefits through several mechanisms, two of which are blocking viral mutation and also blocking viral replication; anti-infectious clinical benefits are proven in humans with HIV/AIDS. The botanical medicine and common herbal tea licorice (Glycyrrhiza glabra) has demonstrated antiviral effectiveness in experimental studies and human clinical trials against several different pathogenic viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), influenza A virus, human immunodeficiency virus (HIV-1), severe acute respiratory syndrome (SARS)-related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus, and vesicular stomatitis virus; this botanical has a an excellent history of safety spanning several thousand years, with adverse/beneficial effects including a pseudoaldosterone effect (sodium retention and potassium depletion) and a testosterone-lowering effect, and mechanism of action including via direct virus binding, inhibition of viral replication, enhancement of immunity, inhibition of inflammation, and blocking the activity of specific enzymes. Antiviral nutrients and botanicals can be used alone, in combination, and alongside medications for additive and synergistic benefits.
2. Blocking viral replication: Inhibition of viral replication is the therapeutic goal of many antiviral drugs, while several nutrients can also provide a similar effect. Because viruses are unable to self-replicate and must therefore rely on host/human genetic and synthetic machinery for their replication, nutrients that modulate genetic expression can have therapeutic value here, namely via DNA methylation (generally causes genes to be "silenced") and blockade of the transcription factor NFkB (an inflammatory pathway used by viruses to promote viral replication). The few nutrients which promote DNA methylation and which also have proven clinical effectiveness against viral infections include folic acid (now used clinically in the forms of folinic acid and methyl-folate), vitamin D3, betaine and S-adenosyl-methionine. Inhibition of the NFkB pathway for antiviral effectiveness is well-proven, with two examples being with NAC against influenza and lipoic acid against viral hepatitis and HIV.
3. Supporting immune function: The performance and regulation of the immune system is heavily dependent on optimal nutritional status, and without proper nutrition, the immune system is slanted simultaneously toward underactivity (deficiency-induced immunosuppression) and hyperactivity manifesting as inflammation and autoimmunity. Nutritional deficiencies are very common in the general population and thereby contribute to epidemics of infectious and inflammatory diseases. Human clinical trials using nutrients alone or in combination to support immune function in general have shown outstanding safety and efficacy against infectious diseases, especially use of glutamine, whey protein isolate, vitamin A, vitamin D, fish oil, and zinc. Nutritional supplementation has been shown in several instances to improve immunological response to vaccinations; for example, cystine and theanine were noted to increase seroconversion of influenza vaccination in elderly persons.
4. Supporting cellular and whole-body health: Viral infections have numerous adverse effects on cellular and whole-body health. Intracellular consequences of viral infections include mitochondrial dysfunction and endoplasmic reticulum stress, manifesting clinically as prolonged inflammation, fatigue and – likely – in the case of herpes simplex infections, Alzheimer's disease. Among the more than 30 interventions to improve mitochondrial function and alleviate endoplasmic reticulum stress, we see that exercise, low-carbohydrate diets, coenzyme Q-10, lipoic acid, and acetyl-L-carnitine are preeminent in their safety, effectiveness, and collateral benefits. Osteopathic manipulative medicine, perhaps via promotion of improved respiration and lymphatic flow and distribution of chemokines, has also shown benefit in the nonpharmacologic amelioration of infectious disease.
In summary, via the use of a structured antiviral strategy, pharmacologic and nonpharmacologic interventions can be applied with greater clinical and public health effectiveness, thereby alleviating the clinical, social, financial, and political burdens of these infectious diseases.
Conclusion and Application
The recent international outbreaks of viral infections have made one thing very clear: we need a new antiviral strategy in modern times to combat ongoing scourges of viral infections; pandemic spread of these infections in late 2014 is proof that the usual medical and public health measures of sanitation, vaccination, and medication are insufficient. The ideal antiviral strategy would be both generally and specifically effective, widely available, low-cost, with few or negligible adverse effects and drug/disease interactions. For most of medical and public health history, the tools used against viral infections have been sanitation and vaccination, with the more recent addition of molecularly-targeted antiviral drugs specific for each virus. My purpose in writing this essay is not to discuss or debate sanitation nor vaccination nor medication, but rather to point out several other intervention strategies that can be used additionally and to great patient and public health benefit. These evidence-based interventions have proven safety, effectiveness, and cost-effectiveness with wide and immediate international availability and generally negligible adverse effects and drug/disease interactions.
Publication history: The primary goal of this article is to outline a more complete strategy to counter the personal and population-wide impacts of viral infections; representative citations supporting these concepts are provided. This article - https://intjhumnutrfunctmed.org/publications/content/IJHNFM_v2q4p1_AntiViralStrategy.pdf - underwent legitimate peer-review by an international interdisciplinary team of professionals. Because this is a conceptual essay, citations to literature have been compiled together for efficiency.
 Digital clinical protocol updated regularly: Vasquez A. Antiviral Nutrition: Against Colds, Flu, Herpes, AIDS, Hepatitis, Ebola, Dengue, and Autoimmunity: A Concept-Based and Evidence-Based Handbook and Research Review for Practical Use. International College of Human Nutrition and Functional Medicine, 2014. (ASIN: B00OPDQG4W). Printed in book format: Vasquez A. Antiviral Strategies and Immune Nutrition. CreateSpace Publishing, 2014. (ISBN: 1502894890)
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 Vasquez A. Functional Inflammology: Volume 1: Introduction to Clinical Nutrition, Functional Medicine, and Integrative Pain Management for Disorders of Sustained Inflammation. International College of Human Nutrition and Functional Medicine, 2014. (ISBN: 9780990620402)
 Vasquez A. F.I.N.D. S.E.X. The Easily Remembered Acronym for the Functional Inflammology Protocol. CreateSpace Independent Publishing, 2013. (ISBN: 1484046765)
 Beck MA. Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 2001 Oct;20(5 Suppl):384S-388S. Beck MA. Nutritionally induced oxidative stress: effect on viral disease. Am J Clin Nutr. 2000 Jun;71(6 Suppl):1676S-81S. Beck MA. Selenium and vitamin E status: impact on viral pathogenicity. J Nutr. 2007 May;137(5):1338-40. Beck MA. Selenium and host defence towards viruses. Proc Nutr Soc. 1999 Aug;58(3):707-11. Hurwitz et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation. Arch Intern Med. 2007 Jan 22;167(2):148-54
 Fiore et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008 Feb;22(2):141-8. Matsumoto et al. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro. PLoS One. 2013 Jul 18;8(7):e68992. Ming LJ, Yin AC. Therapeutic effects of glycyrrhizic acid. Nat Prod Commun. 2013 Mar;8(3):415-8. Bean P. The use of alternative medicine in the treatment of hepatitis C. Am Clin Lab. 2002 May;21(4):19-21. Pompei et al. Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature. 1979;281(5733):689-90. Feng Yeh et al. Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013 Jul 9;148(2):466-73. Cinatl et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003 Jun 14;361(9374):2045-6. Ikeda et al. Prevention of disease progression with anti-inflammatory therapy in patients with HCV-related cirrhosis: a Markov model. Oncology. 2014;86(5-6):295-302. van Rossum et al. Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial. J Gastroenterol Hepatol. 1999 Nov;14(11):1093-9
 Butterworth et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982 Jan;35(1):73-82. See also Butterworth et al. Folate deficiency and cervical dysplasia. JAMA. 1992 Jan 22-29;267(4):528-33. "About 20 percent of women taking contraceptive hormones manifest mild megaloblastic changes on Papanicolaou smears of the cervicovaginal epithelium which disappear after folic acid therapy. The current evidence, however, would not indicate that any significant benefit would ensue from routine folate supplementation in women on oral contraceptives." Lindenbaum et al. Oral contraceptive hormones, folate metabolism, and the cervical epithelium. Am J Clin Nutr. 1975 Apr;28(4):346-53. Knowing what we know now about "folic acid" as a synthetic and pro-oxidative form of the vitamin, these studies should be performed again using folinic acid or methyl-folate. Note negative studies including Childers et al. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol Biomarkers Prev. 1995 Mar;4(2):155-9.
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 Feld et al. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology. 2011 Mar;140(3):830-9. Filipowicz et al. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One. 2010 Nov 8;5(11):e15492
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 "Deficiency in vitamin D is associated with increased autoimmunity and an increased susceptibility to infection." Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-6. Harbige LS. Nutrition and immunity with emphasis on infection and autoimmune disease. Nutr Health. 1996;10(4):285-312. Vasquez A. Naturopathic Rheumatology v3.5. International College of Human Nutrition and Functional Medicine, 2014. (ISBN: 0990620425)
 Micke et al. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest. 2001 Feb;31(2):171-8. Micke et al. Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients. Eur J Nutr. 2002 Feb;41(1):12-8. Moreno et al. Features of whey protein concentrate supplementation in children with rapidly progressive HIV infection. J Trop Pediatr. 2006 Feb;52(1):34-8. Linday et al. Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research. Ann Otol Rhinol Laryngol. 2002 Jul;111(7 Pt 1):642-52. Linday et al. Effect of daily cod liver oil and a multivitamin-mineral supplement with selenium on upper respiratory tract pediatric visits by young, inner-city, Latino children: randomized pediatric sites. Ann Otol Rhinol Laryngol. 2004 Nov;113(11):891-901. The glutamine dose in this study was "a total of 26 g/day" administered in four divided doses. CONCLUSION: "The results of this prospective randomized clinical trial show that enteral G reduces blood culture positivity, particularly with P. aeruginosa, in adults with severe burns and may be a life-saving intervention." Garrel et al. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003 Oct;31(10):2444-9
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 El-Bacha et al. Virus-induced changes in mitochondrial bioenergetics as potential targets for therapy. Int J Biochem Cell Biol. 2013 Jan;45(1):41-6. Anand et al. Viruses as modulators of mitochondrial functions. Adv Virol. 2013;2013:738794. Saffran et al. Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep. 2007 Feb;8(2):188-93. For clinical contexualization of mitochondrial dysfunction in primary care, see: Vasquez A. Mitochondrial medicine arrives to prime time in clinical care: nutritional biochemistry and mitochondrial hyperpermeability ("leaky mitochondria") meet disease pathogenesis and clinical interventions. Altern Ther Health Med. 2014 Winter;20 Suppl 1:26-30 https://inflammationmastery.com/reprints/vasquez_2014_mitochondrial_medicine_editorial.pdf
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 Vasquez A. Mitochondrial Nutrition and Endoplasmic Reticulum Stress in Primary Care, 2nd Edition. CreateSpace Publishing, 2014. (ISBN: 1502952505)
 Creasy et al. Thoracic and abdominal lymphatic pump techniques inhibit the growth of S. pneumoniae bacteria in the lungs of rats. Lymphat Res Biol. 2013 Sep;11(3):183-6. Hodge LM, Downey HF. Lymphatic pump treatment enhances the lymphatic and immune systems. Exp Biol Med (Maywood). 2011 Oct;236(10):1109-15. Noll et al. Adjunctive osteopathic manipulative treatment in the elderly hospitalized with pneumonia: a pilot study. J Am Osteopath Assoc. 1999 Mar;99(3):143-6, 151-2. Noll et al. Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial. Osteopath Med Prim Care. 2010 Mar 19;4:2. Knott et al. Increased lymphatic flow in the thoracic duct during manipulative intervention. J Am Osteopath Assoc. 2005 Oct;105(10):447-56