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Institute of Functional Medicine (IFM), February 17, 2021, Notes written and compiled by Cynthia Li, MD

Freely accessible 90-minute webinar: COVID–19 Vaccines: Current Evidence and Clinical Considerations, video and video transcript


  • Heather Zwickey, PhD, immunologist, Yale post-doc and professor, currently the National University of Natural Medicine in Portland, OR, doing NIH-funded research on natural therapies and nutrition on immunology
  • James Carter, Jr, MD, triple boarded Internal Medicine, cardiology, vascular medicine, an expert on social determinants of disease
  • Patrick Hanaway, MD, IFM faculty, family medicine, head of medical education, and former head of Cleveland Clinic’s FM center
  • Joel Evans, MD, IFM faculty, OB-gyn, an expert on hormones and the immune system


Hanaway summarized the evidence from the current vaccines: COVID-19 Vaccines in Phase 3 Trials

  • Zwickey: vaccines stimulate multiple parts of the immune system.
  • Antibodies (Abs), measurable
  • T-cells, a very important part, not measurable by standard labs; so even if someone doesn’t generate a strong Ab, it doesn’t mean the vaccine didn’t generate a strong response; T-cell response seems more important in protection
  • Cytokines, responsible for the fatigue and fever 1IL=Interleukin, and aches (IL-6, TNF[2]-a) post- vaccine
  • Circadian rhythm of cortisol (highest in AM) may affect vaccine response; the earlier in the day, the more likely to have less of a reaction (this could mean fewer side effects, but may also mean less of an immune response)

The difference in effect between infection with wild-type virus vs vaccine:

  • Infection has a smaller inoculum but the concentration will grow; vaccine is a larger inoculum but there is no growth
  • Both stimulate IgM[3]—>IgG
  • Usually a greater Ab response from wild-type infection

IFM’s hypothesis based on biologic plausibility: pre-emptive improvement of immune function, inflammation, and lifestyle factors will help improve the effectiveness of vaccines and decrease the severity of side-effects. “ATMs” (antecedents, triggers, mediators) Antecedents: genetics, epigenetics, and methylation *improve methylation before vaccine—lots of leafy greens + 5-MTHF [Methyltetrahydrofolate] form of folate supplement Triggers: delay vaccination during an active infection

Mediators (perpetuators):

Examples include dementia, obesity, smoking—try to address them before vaccination to improve the response to vaccination

Systems Optimization


Fiber intake, supporting healthy gut flora–> these positively influence the immune system

Defense & Repair

Reduce inflammation, avoiding vaccination during an uncontrolled autoimmune flare

Communication (hormones)

Testosterone (Testosterone Replacement Therapy, TRT, in men can decrease vaccine responsiveness in influenza vaccines) and estrogen (Estrogen Replacement Therapy, ERT, in women can increase vaccine responsiveness in influenza vaccines)

Mental, emotional, and spiritual factors

affect both the vaccine and immune response

Lifestyle factors

Sleep duration pre-vaccination—a good night’s sleep for the 2-3 days pre-vaccine, as well as after the vaccine Physical fitness can help improve response to the vaccine Nutrition—correcting undernutrition is very important for immune health and may help with the immune response Any acute stressor—much less robust response to vaccines (research: caregivers of dementia patients) Relationships—loneliness affects the response to vaccines

Options to improve physiological function

(*means to consider for conditions of hypertension, diabetes, cardiovascular disease, dyslipidemia, autoimmunity, obesity)

  • Curcumin
  • Resveratrol
  • Quercetin
  • Melatonin
  • Green tea extract*
  • Glutathione or NAC[4]*
  • Andrographis*
  • Berberine*

Options to support immune function

  • Vitamins A, C, D3, E, B6, B12
  • Folate
  • Iron, zinc, copper, selenium
  • Mushrooms
  • Beta-glucans
  • Echinacea
  • Quercetin
  • Resveratrol

Infographic from IFM on Covid Vaccine Prep(From Pandemic Pre-Vaccination Protocol)


[1] IL=Interleukin [2] TNF=Tumor Necrosis Factor [3] Ig=Immunoglobulin [4] NAC=N-Acetyl Cysteine [5] IFN=interferon

Question and Answer Segment

Note: Q and A starts at 63 minutes in the video. This link to the video is cued up to that section (note that it will take a few minutes to upload) The transcript of the Q and A session is at the end of this document.

Dr. Li’s summary of the Q & A session

Do you need a vaccine if you’ve already had Covid-19 illness or test + for Abs?  –Coronaviruses don’t seem to follow the same rules as many other infections where you’re infected, then you’re done. With the previously circulating 4 coronaviruses, even for +Ab or past illness, ~50% of people develop memory responses, and of those people, they can still get re-infected multiple times a year. We don’t know if this current coronavirus behaves the same way, so the recommendation is still to get the vaccine. –If you already had the infection and have a very strong reaction to the first vaccine, that acts like a booster shot. You probably don’t need a second vaccine; you’ve had your second dose. –If you’ve just had Covid illness within the last 1-2 months, wait to get a vaccine. The CDC recommends to wait 90 days. IFM (Dr. Heather Zwickey, PhD) recommends 90 days to 6 months. Should we delay the 2nd dosage for people?  –The reason the vaccines are spaced out the way they are is because that’s how the clinical trials were done. They were rushed for the pandemic and didn’t have time to wait for other trials. What we know from other vaccine trials, like the Hepatitis B vaccine, is that you can push that 2nd dose out 6 months and still get a strong immune response. The general sense right now is that these vaccines are behaving like Hep B vaccines. We just don’t have the data yet. Vaccine and pregnancy? Not a lot of data. ACOG (American College of Obstetrics and Gynecology) and SMFM (The Society for Maternal-Fetal Medicine) have strong statements that say the vaccine should not be withheld, but that it’s also important to have a discussion with each patient. WHO says the vaccine should be withheld unless the patient has a high risk of exposure. What we know is that in animal studies, there’s no toxicity. In women who are pregnant when they contract Covid-19, they have a higher risk of severe infection and death. Several videos suggesting there’s a shared sequence of amino acids in the part of the mRNA that would take the spike protein and embed it into the envelope of the virus, and that this small piece encodes a 4 amino acid sequence is actually shared with the syncytium protein on the trophoblast. However, this sequence is too short to stimulate an immune response; it’s too small to generate an Ab response. There’s no evidence that it has ever happened. The vaccine does not appear to affect fertility for men or women. Do I still need a vaccine if I take good care of myself, take various vitamins, do all the right things, maybe even take ivermectin prophylactically?  –Dr. Joel Evans: there is no data to say with certainty that any of these measures, or these measures taken together, give 95% protection against Covid 19. Biological plausibility (of lifestyle factors and immune optimization) is different than studies that show 95% efficacy. Drs. Carter, Hanaway, and Evans have all chosen and gotten the vaccine. How do we respond to patients who are worried or hesitant about the vaccines? How do you counsel them? (Drs. Carter & Hanaway) –Take the time to hear their stories. It’s not appropriate to rush people into a decision. –Then he shares with them his process and what the risks were for him as well as for those around him. –Vaccines also decrease hospitalizations and disease severity and mortality (especially in places like Israel, where 40% of the population has already been vaccinated) Covid long-haulers now make up 40% of patients who had moderate to severe Covid illness. There’s no data yet on Covid long-haulers and whether the vaccines can reduce this. How long does the mRNA stick around? And the adenovirus vaccine–how long does that stick around? Are there concerns for the mRNAs sticking around for a long time? –mRNA itself is unstable. If you just have normal mRNA, it will be degraded within 20 minutes The lipid that is around the mRNA in the vaccines offers protection and also allows it to be taken into cells. Goes into macrophages in the tissues–> lymph nodes–> T-cell immune response–> all of the mRNA appears to be killed as the macrophages are killed. –in animal models, within 2-3 days, all of the synthetic mRNA is gone. –it’s different for the adenovirus vaccines (i.e. AstraZenca, Sputnik V and the Johnson & Johnson vaccines). Taken up into the macrophage into the lymph nodes–these cells are also going to be killed. But because the adenovirus is a live viral vector, it may stick around for 7 days. In some immunosuppressed people, it may stick around for 3 weeks or longer (data from dengue trials; similar vaccines; the longest duration is 6 months). If I just finished cancer treatment or if I have cancer, is the vaccine going to be somehow problematic and promote recurrence or worsening? Joel Evans: the real issue is that these patients may not have a robust immune response to the vaccine. Most oncologists are recommending patients wait until their treatment period is over (2-3 months). Right now, there is no concern about the vaccine making cancer worse. Autoimmune disease and vaccine risk Yes, while people with autoimmune disease are at higher risk for having an adverse reaction to the vaccine, they’re also more at risk for having moderate to severe Covid-19 illnesses. If people have uncontrolled systemic autoimmunity or having frequent inflammatory flares (SLE, RA, MS)– the likelihood of vaccination influencing a flare is very high. INF[5]-gamma can exacerbate autoimmune disease. For people with controlled autoimmunity, like if they’re on biologics or methotrexate, there is less concern about vaccination. Rheumatologists have been saying for a year now that they’re concerned about Covid leading to long-term consequences. Vaccination seems to be less likely to lead to autoimmunity than Covid, since it’s 1 spike protein vs an entire viral molecule. More Information For a practical summary and guidance on preparing for vaccination to share with your patients, please see the following COVID Strategies/BCCT blog post. Note that this post includes other IFM resources for specific diet, lifestyle, and nutritional supplementation guidance: Preparing to Be Vaccinated: An Integrative Approach About the Author Dr. Cynthia Li is a Functional Medicine physician and author of Brave New Medicine.   Dr. Li is a regular contributor to BCCT, including her writings on Intuition in Cancer Diagnosis and Treatment and her eBook  How to Shield Yourself against COVID-19: Science-Based, Integrative Medicine Strategies for a Once-in-a-Century Pandemic [/av_textblock]



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