Reducing the Risk for Chronic Whiplash-Related Pain

27 Jul

A study published in 2019 found that nearly half of whiplash associated disorders (WAD) sufferers are still symptomatic one year after their injury. Why is that, and what can one do to reduce their risk for chronic WAD symptoms?

The most common source of pain from WAD injuries arises from joint capsules and ligaments, which are tough, tight bands of tissue that hold joints together and help stabilize the cervical spine. When these soft tissues are damaged, the body will take measures to restrict movement so that the injury doesn’t become more severe. This is one reason why cervical range of motion is reduced when the neck is injured.

You may recall that a patient with whiplash used to be fitted with a cervical collar to protect the neck and limit movement. However, researchers have since discovered that, in many cases, restricting all cervical movement for a prolonged period of time can lead to a weakening of the deep neck muscles—which are important for maintaining cervical posture—and the buildup of potentially troublesome scar tissue. These days, patients are encouraged to remain active provided their movements do not generate acute pain. Not only does staying active reduce the risk of deep neck muscle atrophy, but movement is necessary to produce the compressive forces that help maintain the flow of nutrients to the cartilaginous tissues in the neck.

The back-and-forth whiplash process can also result in trauma to the brain, also known as a concussion. The brain is suspended in the skull by ligaments and is cushioned by fluid. In a rear-end collision, the oblique angle of the chest restraint results in a twisting of the torso upon impact as the body accelerates forward. The brain slams into the front inside of the skull and then rebounds and hits the back inside of the skull as the trunk is forced backward during the deceleration phase of the injury. Depending on the degree of force, concussion can involve the front, back, or both parts of the brain resulting in memory problems, confusion, fatigue/drowsiness, dizziness, vision problems, headache, nausea/vomiting, light/noise sensitivity, and more. The good news is that chiropractic care applied to the cervical spine has been demonstrated to benefit patients with these post-concussive symptoms that often accompany WAD, which may reduce the chances that such symptoms become chronic in nature. The current research suggests that patients who seek treatment soon after a whiplash event— like a car accident, slip and fall, or sports collision—are not only more likely to experience a faster recovery but they are also less likely to develop a chronic condition. Chiropractic care offers a safe and conservative form of treatment for WAD that is often recommend by treatment guidelines.

This information should not be substituted for medical or chiropractic advice. Any and all healthcare concerns, decisions, and actions must be done through the advice and counsel of a healthcare professional who is familiar with your updated medical history.

Neck Pain Among Office Workers

23 Jul

Neck pain is the second most common reason patients seek chiropractic care, and it’s particularly a problem with office workers. One study estimated that neck pain affects 42-69% of those who work in office environments. Many such individuals will experience recurring episodes of neck pain, and at least one in six may develop chronic, ongoing neck pain. While chiropractic offers a safe and effective way to manage neck pain, are there any steps an office worker can take to reduce the risk for neck pain in the first place?

According to one study, taking a daily walk may be an effective neck pain prevention strategy. In the study, which included 387 office workers without spinal symptoms in the previous three months, researchers asked participants to wear a pedometer and note any spinal pain symptoms over the next year.

Of the 367 participants who completed the study, 16% reported the onset of neck pain. The results showed that for every 1,000 steps a participant averaged each day, their risk for neck pain fell by 14%. The authors concluded that increasing daily walking steps is protective for the onset of neck pain in those who work sedentary jobs, and managers should formulate and test strategies to encourage walking to reduce the incidence of neck pain among employees.

What about other forms of exercise? A meta-analysis of data from two randomized control trials that included over 500 participants showed moderate-quality evidence that participating in a workplace exercise program can reduce the risk for developing a new episode of neck pain by up to 68%. In the first trial, participants performed stretching and endurance training twice a day at work and twice a day at home. The second trial involved a combination of strength, stabilization, aerobic, and body awareness exercises that included health information, ergonomic training, and stress management training three times a week for one hour over a nine-month time frame.

While it’s not possible to completely avoid a condition like neck pain, the evidence suggests that regularly engaging in physical activity may substantially lower the risk. For those who do develop neck pain, it’s important to seek chiropractic care as soon as possible, which may lead to a faster resolution of symptoms and reduce the risk for both neck pain recurrence and chronic neck pain.

This information should not be substituted for medical or chiropractic advice. Any and all healthcare concerns, decisions, and actions must be done through the advice and counsel of a healthcare professional who is familiar with your updated medical history.

Footwear Changes for the Knee Osteoarthritis Patient

20 Jul

Osteoarthritis (OA) is the leading cause of knee pain and disability in the elderly population. While treatment to address knee OA will often focus on the knee itself, a patient may also need to change their footwear. Why is that?

During normal walking, joint loading is NOT evenly distributed, and the distribution most often greatest on the medial (inner) side of the knee. This greater load can cause  wear and tear over time and lead to thinning of the smooth, slippery cartilage surfaces on the medial side of the joint, which eventually leads to bone-on-bone contact, the end-stage of OA. By changing where joint loading occurs on the knee, it’s possible to slow this process and potentially delay or even prevent the need for a knee joint replacement.

This can be accomplished through either a change in footwear or adding an insole or orthotic to an existing shoe. On the footwear front, an OA patient may need to avoid clogs, barefoot shoes, high heels, and extra-rigid/stiff shoes. Rather, walking or running shoes or, for more formal occasions, a shoe with a shock-absorbing sole and padded collars that’s not too rigid may be a better choice. A well-trained employee at a specialty shoe store can help identify which shoes will work best for your situation.

One study investigated the use of lateral wedges both with and without custom arch supports for people with medial knee osteoarthritis (OA) and pronation (rolled in feet). Each of the 26 participants wore one or the other for two months and switched to the other option after a two-month “washout” or rest period. The researchers concluded that the lateral heel wedge WITH foot orthotic/arch supports provided the best benefit to the participants with respect to performance on a timed stair climb test. Another study found that adding a mobility shoe reduced medial joint loading to an even greater degree.

For the knee OA patient, chiropractic treatment may also include specific exercise training, weight management/nutrition, manual therapies, modality use (electrical stim, magnetic field, laser, ultrasound, and more), and the use of a knee brace—all in the effort to reduce pain and improve mobility.

This information should not be substituted for medical or chiropractic advice. Any and all healthcare concerns, decisions, and actions must be done through the advice and counsel of a healthcare professional who is familiar with your updated medical history.

Repetitive Movement and Carpal Tunnel Syndrome

16 Jul

Of all the potential contributing factors for carpal tunnel syndrome—diabetes, thyroid dysfunction, inflammatory arthritis, pregnancy, birth control usage, and obesity—perhaps the most well-known is participating in jobs and activities that require fast, repetitive hand movements that can place increased pressure on the median nerve as it passes through the wrist. What can someone do if they begin experiencing tingling and numbness or pain and weakness associated with carpal tunnel syndrome without giving up their livelihood or their hobby?

First, understand that when the wrist is bent, the pressure on the contents of the carpal tunnel can increase substantially, especially when inflammation is present, which can affect the median nerve. So, if an activity frequently leads to numbness, tingling, or painful sensations in the hand and wrist, look for ways to maintain more neutral wrist posture. This may also involve using tools with a more ergonomic, wrist-friendly design. For the carpal tunnel syndrome patient, a doctor of chiropractic may also recommend wearing a splint overnight to keep the wrist from bending during sleep.

It’s also important to take frequent breaks (every 30 minutes, for example) to allow the affected wrist and hand to rest. Or if possible, switch to a different activity for a short time before returning to the task that places the greatest strain on the wrist.

Here are three great exercise options to improve finger, thumb, wrist, and forearm flexibility, which may stretch the soft tissues in the wrist and increase activity tolerance:

  1. Thumb-finger “push-ups”: Place the pads of your fingers and thumbs together in front of you and keep the fingers straight, spread apart, and pointing down. Push the hands together (try to touch your palms) and then push them apart by flexing your fingers and repeat. This stretches all five digits and the palm/forearm muscles ALL at the same time.
  2. Shake ‘em out: …as if you’re shaking your wet hands to dry them. Continue this for as long as one to two minutes every hour.
  3. Wall-stretches: Place your palm on a wall, elbow straight, fingers pointed down and push your palm flat into the wall as far as you can. Reach over and pull your thumb back off the wall with your other hand and hold for 20-30 seconds. Switch hands and repeat the stretch. This can be repeated two to three times per hand every hour.

Of course, consult with your doctor of chiropractic so that he or she can take a look at your patient history and examine the entire course of the median nerve to identify any other factors that may contribute to your carpal tunnel syndrome-associated symptoms.

This information should not be substituted for medical or chiropractic advice. Any and all healthcare concerns, decisions, and actions must be done through the advice and counsel of a healthcare professional who is familiar with your updated medical history.

A Link Between Back Pain and Urinary Incontinence

14 Jul

While under chiropractic treatment, it’s not uncommon for a patient to report improvement for an issue that seems unrelated to their chief complaint. For example, a patient with a temporomandibular disorder may experience an improvement in their jaw symptoms following treatment to the neck or upper back. Or treatment to improve hip function may also benefit the ankle or knee. In this article, we’re going to look at how treatment for low back pain may help a patient who also has urinary incontinence (UI) issues.

There are many potential causes for UI, but one contributing factor is weak pelvic floor muscles. Thus, it makes sense that treatment to address impaired pelvic function may benefit some UI patients. A 2018 Cochrane systemic review concluded that pelvic floor muscle training (PFMT) is more effective than either a sham treatment (placebo) or no treatment for some individuals with UI.

This is where back pain comes into play. It’s estimated that back pain will affect more than 80% of us during our lifetime. We often adjust how we perform everyday activities to avoid pain, both consciously and unconsciously. These abnormal movements can place added stress on other parts of the body. In the case of the lower back, altered function in the hips and pelvis is common.

A November 2019 study published in the Journal of Craniovertebral Junction & Spine concluded that individuals with lumbar degenerative disk disease, spondylolisthesis, and failed back surgery syndrome are more likely to exhibit abnormal spino-pelvic alignment. Overtime, these individuals can develop secondary conditions in the hip or pelvis, which can impair the function of soft tissues, including muscles, in the region. Or likewise, injury to the hips/pelvis can lead to dysfunction in the lower back, which may be why the patient sought care in the first place.

Doctors of chiropractic are trained to review a patient’s case history and conduct a thorough examination on the whole patient in order to identify contributing factors for the patient’s chief complaint. Hence the importance of noting all symptoms, even those that seem unrelated or may be embarrassing. If a low back pain patient’s history notes UI and the examination identifies abnormal pelvic posture, then treatment will likely address improving function in both the pelvis and low back to achieve a successful outcome.

This information should not be substituted for medical or chiropractic advice. Any and all healthcare concerns, decisions, and actions must be done through the advice and counsel of a healthcare professional who is familiar with your updated medical history.

Integrative Considerations during the COVID-19 pandemic

27 Mar

March 24, 2020

Greetings Friends, 

The following is advice from top experts in the natural medicine industry. I found the information here to be valuable and hope you do too. I have been following these health officials in addition to the resources being released by the W.H.O. Also, PA.Gov (or your corresponding state) is a valuable resource for checking on potential local breakouts. 

The importance of not only physical but also mental health should be acknowledged. Reducing or eliminating sensationalized media outlets from your mental diet will benefit your overall health. The WHO and state websites are more than proficient for your data acquisition. 

Particular attention should be given to WHAT NOT TO TAKE DURING INFECTION. Remember that symptoms of COVID-19 can be mild. But it is still important not to take anything that promotes it’s virulence in yourself and therefore the community at large. 

Here is the Integrative Health Strategy information that I currently recommend…

Using available in-vitro evidence, an understanding of the virulence of COVID-19, as well as data from similar, but different, viruses, we offer the following strategies to consider. Again, we stress that these are supplemental considerations to the current recommendations that emphasize regular hand washing, physical distancing, stopping non-essential travel, and getting tested if you develop symptoms. 

While the pathogenicity of COVID-19 is complex, it is important to understand the role of inflammation in this disease. The virulence and pathogenicity (including acute respiratory distress syndrome) associated with SARS corona viruses develops as the result of viral activation of cytoplasmic NLRP3 inflammasome. This inflammasome within activated (upregulated NFkB) macrophages and Th1 immune cells releases pro-inflammatory cytokines, namely IL-1B and IL- 18, which dictate the pathogenic inflammation responsible for the virulence and symptoms of COVID-19.1 Understanding this component of COVID-19 infection provides a mechanistic underpinning to several of the following.

RISK REDUCTION:
• Adequate sleep: Shorter sleep duration increases the risk of infectious illness. One study found that less than 5 hours of sleep (monitored over 7 consecutive days) increased the risk of developing rhinovirus associated cold by 350% (odds ratio [OR] = 4.50, 95% confidence interval [CI], 1.08-18.69) when compared to individuals who slept at least 7 hours per night.2 Important to COVID-19, sleep deprivation increases CXCL9 levels. CXCL9 is a monokine, induced by interferon, and which increases lymphocytic infiltration,3 and which is implicated in NLRP3 inflammasome activation.4 Adequate sleep also ensures the secretion of melatonin, a molecule which may play a role in reducing coronavirus virulence (see Melatonin below).
• Stress management: Psychological stress disrupts immune regulation and is specifically associated with increased pro-inflammatory cytokines such as IL-65 Acute stress in mice increases IL-1B via NLRP3 inflammasome activation.6 Various mindfulness techniques such as meditation, breathing exercises, guided imagery, etc. reduce stress, reduce activated NFkB, may reduce CRP and do not appear to increase inflammatory cytokines.7 
• Zinc: Coronavirus appears to be susceptible to the viral inhibitory actions of zinc. Zinc may prevent coronavirus entry into cells8 and appears to reduce coronavirus virulence.9 Typical daily dosing of zinc is 15mg – 30mg daily with lozenges potentially providing direct protective effects in the upper respiratory tract.
• Vegetables and Fruits +/- isolated Flavonoids: Many flavonoids have been found, in vitro, to reduce NLRP3 inflammasome signaling, and consequently NFkB, TNF-a, IL-6, IL-1B and IL-18 expression.10

Some of the specific flavonoids which have been shown to have this effect, and which can be found in the diet and/or dietary supplements include: 

  •  baicalin11 and wogonoside12 from Scutellaria baicalensis (Chinese skullcap);
  •  liquiritigenin13 from Glycyrrhiza glabra (licorice)
  • dihydroquercetin14 and quercetin15 found in onions and apples. Of note, quercetin also functions as a zinc ionophore, chelating zinc and transporting it into the cell cytoplasm.16 This could, theoretically, enhance the anti-viral actions of zinc.
  •  myricetin17 found in tomatoes, oranges, nuts, and berries
  • oapigenin18 (found in Matricaria recutita (Chamomile), parsley and celery.
  • ocurcumin19,20 (found in turmeric root)
  • epigallocatechine gallate (EGCG) from green tea. EGCG has been found to have antiviral activity against a wide range of DNA and RNA viruses, especially in the early stages of infection by preventing viral attachment, entry and membrane fusion.21 EGCG, link quercetin, is a zinc ionophore22, thereby potentially enhancing the antiviral actions of zinc.

At least 5 – 7 servings of vegetables and 2-3 servings of fruit daily provide a repository of flavonoids and are considered a cornerstone of an anti-inflammatory diet.

• Vitamin C: Like flavonoids, ascorbic acid inhibits NLRP3 inflammasome activation.23 Clinical trials have found that vitamin C shortens the frequency, duration and severity of the common cold and the incidence of pneumonia.24 Typical daily dosing of vitamin C ranges from 500mg to 3000mg daily with even higher doses utilized during times of
acute infection.

• Melatonin: Melatonin has been shown to inhibit NFkB activation and NLRP3 inflammasome activation.25 In fact, the age-related decline in melatonin production is one proposed mechanism to explain why children do not appear to have severe symptoms and older adults do. Melatonin also reduces oxidative lung injury and inflammatory cell recruitment during viral infections.26 Typical dosing of melatonin varies widely from 0.3mg to 20mg (the latter used in the oncological setting).

• Sambucus nigra (Elderberry): There is preclinical evidence that elderberry inhibits replication and viral attachment of Human coronavirus NL63 (HCoV-NL63)27, different than COVID-19, but a member of the coronavirus family. Sambucus appears most effective in the prevention or early stage of corona virus infections.28
******Of note, Sambucus significantly increases inflammatory cytokines, including IL-B129 so should be discontinued with symptoms of infection (or positive test). An evidence-based systematic review of elderberry conducted by the Natural Standard Research Collaboration concluded that there is level B evidence to support the use of elderberry for influenza30 which may or may not be applicable to COVID-19 prevention. Typical dosing of 2:1 elderberry extract is 10mL -60mL daily for adults and 5mL-30mL daily for children.

• Vitamin D: In certain conditions, vitamin D has been found to decrease NLRP3 inflammasome activation31 and vitamin D receptor activation reduces IL-1b secretion.32 However, 1,25(OH)vitamin D has also been found to increase IL-1b levels,33,34 and should, therefore, be used with caution and perhaps discontinued with symptoms of infection.

DURING SYMPTOMS OF INFECTION OR POSITIVE TEST FOR COVID-19:
To Avoid: Given the integral role of inflammatory cytokines (namely IL-1B and IL-18) in the pathogenicity of COVID-19, as well as the impossibility of predicting which individuals are susceptible to the “cytokine storm”, technically called secondary hemophagocytic lymphohistiocytosis, or sHLH, it appears to be prudent to avoid high and regular use of immunostimulatory agents that increase these cytokines.

Again, in the absence of human clinical data, caution is warranted with the following immune-activating agents due to preclinical evidence of increased IL-1B and/or IL-18 production in infected immune cells:
! Sambucus nigra (Elderberry)35
! Isolated polysaccharide extracts from medicinal mushrooms or mycelium36,37
! Echinacea angustifolia and E. purpurea38,39
! Larch arabinogalactan40
! Supplemental vitamin D41,42

Likely Safe: Other commonly used natural immunostimulatory and antiviral agents including the following do not appear to increase IL-1B or IL-18 as a part of their immunomodulatory actions. Several of these, in fact, reduce these cytokines and may restore immune homeostasis. These are, therefore, likely safe to use both prior to, and during, COVID-19 infection. Whether these agents mitigate the symptoms or virulence of COVID-19 is unknown and therefore the benefit of these agents during COVID-19 infection is unknown.
• Allium sativum (garlic)
• Quercetin
• Astragalus membranaceus
• Mycelium mushroom extracts as well as fruiting body extract of Agaricus blazeii49
• Mentha piperita (peppermint)
• Andrographis paniculata
• Green tea and green tea extracts
• Zinc
• Vitamin A [note: This study found that 25,000iu daily for 4 months in 84 women resulted in lower serum IL-1b and IL-1b/IL-4 ratios in obese women. Oral vitamin A can causes hypervitaminosis A especially at doses greater than 25,000 IU daily for more than 6 years or 100,000iu daily for more than 6 months. Monitoring liver function tests for hepatotoxicity during vitamin A dosing of any duration, even at lower doses, is advised given variable individual sensitivity.]
• Vitamin C

The information and understanding of COVID-19 continue to change rapidly. We encourage you to make integrative recommendations carefully and with consideration of the underlying mechanisms of both the COVID-19 infection and the intended intervention. It is also important to reiterate that there are no clinically evidence-based integrative prevention or treatment strategies for COVID-19 infection. 

Lise Alschuler ND
Professor of Clinical Medicine, University of Arizona College of Medicine Assistant Director, Fellowship in Integrative Medicine,
Andrew Weil Center for Integrative Medicine

Reviewed by:
Ann Marie Chiasson MD
Associate Professor of Clinical Medicine, University of Arizona College of Medicine
Director, Fellowship in Integrative Medicine, Andrew Weil Center for Integrative Medicine

Robert Crocker MD
Assistant Professor of Medicine, University of Arizona College of Medicine
Director, Strategic and Clinical Planning and Implementation,

Andrew Weil Center for
Integrative Medicine3

Randy Horwitz MD PhD FACP
Professor of Medicine, University of Arizona College of Medicine
Medical Director,

Andrew Weil Center for Integrative Medicine
Victoria Maizes MD
Professor of Clinical Medicine, Family Medicine and Public Health, University of Arizona

Andrew Weil Endowed Chair in Integrative Medicine
Executive Director, Andrew Weil Center for Integrative Medicine

Paul Stamets
Mycologist

Andrew Weil MD
Professor of Medicine and Public Health, University of Arizona
Endowed Chair in Integrative Rheumatology, University of Arizona
Founder,

Andrew Weil Center for Integrative Medicine
Media inquires please contact Keith LaBaw, Manager, AWCIM Marketing at
klabaw@arizona.edu

1 Chen, I-Y, et al. Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3
Inflammasome. Front Microbiol. 2019;10:50.

2 Prather AA, et al. Behaviorally Assessed Sleep and Susceptibility to the Common Cold. Sleep. 2015;38(9):1353-9.

3 Gorbachev AV, et al. CXC chemokine ligand 9/monokine induced by IFN-gamma production by tumor cells is
critical for T cell-mediated suppression of cutaneous tumors. J Immunol. 2007;178:2278–2286.

4 Romero, JM, et al. A Four-Chemokine Signature Is Associated With a T-cell-Inflamed Phenotype in Primary and
Metastatic Pancreatic Cancer. Clin Cancer Res. 2020 Jan 21 [online ahead of print]

5 Godbout JP, Glaser R. Stress-induced Immune Dysregulation: Implications for Wound Healing, Infectious Disease
and Cancer. J Neuroimmune Pharmacol. 2006;1(4):421.

6 Iwata M, et al. Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and
Stimulation of the Purinergic Type 2X7 Receptor. Biol Psychiatry. 2016;80(1):12.

7 Black D and Slavich GM. Mindfulness meditation and the immune system: a systematic review of randomized
controlled trials. Ann NY Acad Sci. 2016;1373(1):13.
8 Phillips JM, et al. Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry
and Cell-Cell Fusion. J Virol. 2017;91(8).

9 Han Y-S, et al. Papain-like Protease 2 (PLP2) From Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV):
Expression, Purification, Characterization, and Inhibition. Biochemistry. 2005;44(30):10349.

10 Lim H, et al. Flavonoids Interfere with NLRP3 Inflammasome Activation. Toxicol Appl Pharmacol. 2018;355:93.

11 Fu S, et al. Baicalin Suppresses NLRP3 Inflammasome and Nuclear Factor-Kappa B (NF-κB) Signaling During
Haemophilus Parasuis Infection. Vet Res. 2016;47(1):80.

12 Sun Y, et al. Wogonoside Protects Against Dextran Sulfate Sodium-Induced Experimental Colitis in Mice by
Inhibiting NF-κB and NLRP3 Inflammasome Activation. Biochm Pharmacol. 2015;94(2):142.

13 Zhu X, et al. Liquiritigenin Attenuates High Glucose-Induced Mesangial Matrix Accumulation, Oxidative Stress,
and Inflammation by Suppression of the NF-κB and NLRP3 Inflammasome Pathways. Biomed Pharmacother.
2018;106:976.

14 Ding T, et al. Kidney Protection Effects of Dihydroquercetin on Diabetic Nephropathy Through Suppressing ROS
and NLRP3 Inflammasome. Phytomedicine. 2018(41):45.

15 Choe J-Y, et al. Quercetin and Ascorbic Acid Suppress Fructose-Induced NLRP3 Inflammasome Activation by
Blocking Intracellular Shuttling of TXNIP in Human Macrophage Cell Lines. Inflammation. 2017;40(3):980.

16 Dabbagh-Bazarbachi H, et al. Zinc Ionophore Activity of Quercetin and Epigallocatechin-Gallate: From Hepa 1-6
Cells to a Liposome Model. J Agric Food Chem. 2014;62(32):8085-93.

17 Chen H, et al. Myricetin Inhibits NLRP3 Inflammasome Activation via Reduction of ROS-dependent Ubiquitination
of ASC and Promotion of ROS-independent NLRP3 Ubiquitination. Toxicol Appl Pharmacol. 2019;365:19.

18 Yamagata K, et al. Dietary Apigenin Reduces Induction of LOX-1 and NLRP3 Expression, Leukocyte Adhesion, and
Acetylated Low-Density Lipoprotein Uptake in Human Endothelial Cells Exposed to Trimethylamine-N-Oxide. J
Cardiovasc Pharmacol. 2019;74(6):558.

19 Yin H, et al. Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3
Inflammasome. J Immunol. 2018;200(8):2835.

20 Wen CC, et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute
respiratory syndrome coronavirus. J Med Chem. 2007;50(17):4087.

21 Kaihatsu K, et al. Antiviral Mechanism of Action of Epigallocatechin-3- O-gallate and Its Fatty Acid Esters.
Molecules. 2018;23(10):2475.

22 Dabbagh-Bazarbachi H, et al. Zinc Ionophore Activity of Quercetin and Epigallocatechin-Gallate: From Hepa 1-6
Cells to a Liposome Model. J Agric Food Chem. 2014;62(32):8085-93.

23 Choe J-Y, et al. Quercetin and Ascorbic Acid Suppress Fructose-Induced NLRP3 Inflammasome Activation by
Blocking Intracellular Shuttling of TXNIP in Human Macrophage Cell Lines. Inflammation. 2017;40(3):980.

24 Hemila, H. Vitamin C Supplementation and Respiratory Infections: A Systematic Review. Mil Med.
2004;169(11):90.

25 Hardeland, R. Melatonin and inflammation – Story of a Double-Edged Blade. J Pineal Res. 2018;65(4):e12525.

26 Silvestri M and Rossi GA. Melatonin: its possible role in the management of viral infections – a brief review. Ital J
Pediatr. 2013;39:61.

27 Weng J-R, et al. Antiviral Activity of Sambucus FormosanaNakai Ethanol Extract and Related Phenolic Acid
Constituents Against Human Coronavirus NL63. Virus Res. 2019;273:197767.

28 Chen C, et al. Sambucus Nigra Extracts Inhibit Infectious Bronchitis Virus at an Early Point During Replication.
BMC Vet Res. 2014:10:24.

29 Barak V, et al. The Effect of Sambucol, a Black Elderberry-Based, Natural Product, on the Production of Human
Cytokines: I. Inflammatory Cytokines. Eur Cytokine Netw. 2001;12(2):290.

30 Ulbricht C, et al. An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus nigra) by the
Natural Standard Research Collaboration. J Dietary Suppl. 2014;11(1):80.

31 Lu L, et al. Vitamin D 3 Protects Against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of
the ROS/TXNIP/NLRP3 Inflammasome Pathway. J Diabetes Res. 2018:8193523.

32 Rao Z, et al. Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination.
Front Immunol. 2019;10:2783.

33 Verway M, et al. Vitamin D Induces interleukin-1β Expression: Paracrine Macrophage Epithelial Signaling
Controls M. Tuberculosis Infection. PLoS Pathog. 2013;9(6):e1003407.

34 Tulk SE, et al. Vitamin D3 Metabolites Enhance the NLRP3-dependent Secretion of IL-1β From Human THP-1
Monocytic Cells. J Cell Biochem. 2015;116(5):711.

35 Barak V, et al. The Effect of Sambucol, a Black Elderberry-Based, Natural Product, on the Production of Human
Cytokines: I. Inflammatory Cytokines. Eur Cytokine Netw. 2001;12(2):290.

36 Yang Y, et al. Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation. Innate
Immun. 2014;20(8):857.

37 Ma XL, et al. Immunomodulatory activity of macromolecular polysaccharide isolated from Grifola frondosa. Chin
J Nat Med. 2015;13(12):906.

38 Burger RA, et al. Echinacea-induced Cytokine Production by Human Macrophages. Int J Immunopharmacol.
1997;19(7):371.

39 Senchina DS, et al. Human Blood Mononuclear Cell in Vitro Cytokine Response Before and After Two Different
Strenuous Exercise Bouts in the Presence of Bloodroot and Echinacea Extracts. Blood Cells Mol Dis. 2009;43(3):298.

40 Hauer J, Anderer FA. Mechanism of Stimulation of Human Natural Killer Cytotoxicity by Arabinogalactan From
Larix Occidentalis. Cancer Immunol Immunother. 1993;36(4):237.

41 Verway M, et al. Vitamin D Induces interleukin-1β Expression: Paracrine Macrophage Epithelial Signaling
Controls M. Tuberculosis Infection. PLoS Pathog. 2013;9(6):e1003407.

42 Tulk SE, et al. Vitamin D3 Metabolites Enhance the NLRP3-dependent Secretion of IL-1β From Human THP-1
Monocytic Cells. J Cell Biochem. 2015;116(5):711.

43 Arreola R, et al. Immunodulation and Anti-Inflammatory Effects of Garlic Compounds. J Immunol Res.
2015;2015:401630.

44 Mlcek J, et al. Quercetin and Its Anti-Allergic Immune Response. Molecules. 2016;21(5):623.

45 He, X, et al. Inhibitory Effect of Astragalus Polysaccharides on Lipopolysaccharide-Induced TNF-a and IL-1β
Production in THP-1 Cells. Molecules. 2012; 17(3): 3155.

46 Li H, et al. Astragaloside Inhibits IL-1β-induced Inflammatory Response in Human Osteoarthritis Chondrocytes
and Ameliorates the Progression of Osteoarthritis in Mice Immunopharmacol Immunotoxicol. 2019;421(4):497.

47 Davis R, et al. Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous,
Ethanol, and Solid Fractions of a Medicinal Mushroom Blend. J Inflammation Res. 2020;13:117.

48 Benson KF, et al.The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate
each show potent and complementary immune activating properties in vitro. MC Complementary and Alternative
Medicine. 2019;19:342.

49 Tangen J-M. Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in
Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation:
A Randomized, Double Blinded Clinical Study. BioMed Res Int. 2015;2015:718539.

50 Li Y, et al. In Vitro Antiviral, Anti-Inflammatory, and Antioxidant Activities of the Ethanol Extract of Mentha
piperita L. Food Sci Biotechnol. 2017;26(6):1675.

51 Chandrasekaran CV, et al. In Vitro Comparative Evaluation of Non-Leaves and Leaves Extracts of Andrographis
Paniculata on Modulation of Inflammatory Mediators. Antiinflamm Antiallergy Agents Med Chem. 2012;11(2):191.

52 Ge M, et al. Multiple Antiviral Approaches of (-)-epigallocatechin-3-gallate (EGCG) Against Porcine Reproductive
and Respiratory Syndrome Virus Infection in Vitro. Antiviral Res. 2018;158:52-62.

53 Ahmed S, et al. Green Tea Polyphenol epigallocatechin-3-gallate Inhibits the IL-1 Beta-Induced Activity and
Expression of cyclooxygenase-2 and Nitric Oxide synthase-2 in Human Chondrocytes. Free Radic Biol Med.
2002;33(8):1097.

54 Han Y-S, et al. Papain-like Protease 2 (PLP2) From Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV):
Expression, Purification, Characterization, and Inhibition. Biochemistry. 2005;44(30):10349.

55 Farhangi MA, et al. Vitamin A Supplementation and Serum Th1- And Th2-associated Cytokine Response in
Women. J Am Coll Nutr. 2013;32(4):280.

56 Penniston KL and Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;
83(23):191.

57 Choe J-Y, et al. Quercetin and Ascorbic Acid Suppress Fructose-Induced NLRP3 Inflammasome Activation by
Blocking Intracellular Shuttling of TXNIP in Human Macrophage Cell Lines. Inflammation. 2017;40(3):980.

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