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HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
1
Health & Immunity: A Natural Perspective for a New Paradigm - Part 2
Dr Silverman: Thanks so much Dr Grisanti. I’m happy to be here and thank
everybody so much for coming back to part 2, we had a great turnout in part 1, we
had a ton of questions, a lot of concerns. Hopefully in the last 2 weeks a lot of people
are getting a better grip on this health pandemic. Once again, you have all my
information here to contact me. I encourage that, I encourage you to contact Dr
Grisanti through FMU, follow us on Facebook, we get a lot of DM questions those
are always very easy.
This is a newly updated presentation. I’m going to share some leading edge natural
approaches to improving ours, our patients’ health, our family and our friends’ health
through immune boosting strategies and much more. I really understand with the
advent of this new research and protocols surrounding this viral pandemic many
practitioners including myself are not seeing patients in person, we are seeing in
telehealth. And I can tell you this conversation piece, these protocols are great.
Nutrition is easy on telehealth and I strongly recommend it. And I’m here to help you
understand the etiology of the health pandemic and possibly the best direction to
take with your patient base now. So without any further delay let’s dig in on it. Like Dr
Grisanti says, I’m not in a rush today so if we go over a few minutes please I thank
you for your patience in advance, we are going to answer all the questions that we
possibly can.
COVID-19 can’t gain entry to our homes or bodies by itself
So I thought this was great, it was an article from the Guardian April 10th, importantly
COVID-19 cannot gain entry into our homes or our bodies by itself, we have to let it
in. So even if it is on our shirt or on our hand as long as it is not pushed into our oral
nasal pharynx we are ok and that is why this breathing and proverbial idea of
physical social distancing is so important. So please the literature since the last time
is even more stacked wear the mask when you are in public, wear your gloves.
Wash your hands for 20 seconds or more as we all talked about that, soap breaks up
that fat bond in the virus, remember a brief overview we covered it in part 1, viruses
are not live they are either activated or inactivated. Washing your hands for 20
seconds or more with soap, soap being a fat breaks the fat bi-layer and inactivates
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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the virus as it washes down. Use all your typical antiseptics, again physical
distancing. Many of the stores that you can shop in are doing a great job, if you have
takeout or delivery if you will, wear your gloves, leave it outside, open up what you
need in the food, bring it in, wash the counter down. Just be careful, don’t get
frustrated we are all going to come out of this.
27ft for distancing
So now they are talking about 27 feet for social distancing because when you
sneeze, cough and the such it is a turbulent gas cloud and the pathogen bearing
droplets of all sizes can travel up to 23-27 feet and that is why you want people to
wear a mask because if they have it and they don’t know it they won’t pass it
because the mask will protect you from them.
Underlying conditions among adults hospitalized with COVID-19
So the colors red, blue, and yellow depict different age groups. So interesting, this
was for the month of March, the number 1 reason why people went in in the age
group over 60 was hypertension. From the age groups from 50-64 and 18-49
respective age groups the number 1 reason why they saw or their comorbidity that
led them in was obesity. So when you look at these, you are looking at interesting
cardiovascular disease, diabetes, maybe not or maybe (it is going to be an
interesting conversation that we are going to have at the end) chronic lung disease,
obesity and hypertension. Would it be fair to say that so many of these comorbidities
are wrapped around the theme of lifestyle? So now we know from the last
presentation the different protocols to use for immune boosting. Maybe now we’ve
got to get to lifestyle and maybe now also as I’ll make big point once again, maybe
now lifestyle includes not just exercise and supplements and sleep, maybe it
includes some gut health. Many of these comorbidities can be directly related to
lifestyle faults.
90% of COVID-19 admissions involve comorbidities
The hospitalization rate, 89.3% of patients hospitalised it was a comorbidity, about
90%. And you see the numbers if you are over 65 it is high almost double than 50-
64, and 50-64 is 3 times bigger than 18-49. Please don’t miss, some of these
younger people still inevitably still have to go into the hospital. So with one or more
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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underlying conditions or comorbidities virtually everybody who is admitted to the
hospital had more than one, they were sick. Hypertension being the number one
comorbidity 72.6%. CVD slightly over 50% and obesity 41%. Once again, to reiterate
what I said earlier, younger groups number one reason that they are in from 65 or
less is obesity, 65 and older hypertension.
Leading comorbidities among COVID-19 deaths in New York
86.2% of the state’s deaths at that point involved at least one comorbidity, number
one was hypertension. Number two was diabetes. The rate of hospitalisation for
COVID-19 increased with age, not a real surprise we kind of saw the delineation
before but now they took it up to 75-84 and over 85, so the takeaway here is
everyone especially older adults should stay home if you can - physical and social
distance, use face coverings in public settings, wash your hands and start leading a
healthy lifestyle.
COVID-19
On average and this was a little disconcerting when I read this, only 6% of SARS-
CoV-2 infections detected worldwide. The actual number of infections may already
have reached several 10s of millions. Basically we just haven’t tested enough
worldwide to really know how many have been exposed and infected.
Now, between March 22nd and April 4th 2020, a total of 215 pregnant women
delivered infants and it was New York Presbyterian hospital and Columbia
University. All of the women were screened on admission for symptoms of COVID-
19, 4 women which is less than 2%, (1.9), had fever or other symptoms of COVID-19
on admission and all 4 women tested positive for COVID too. Of the 211 women
without symptoms all were afebrile on admission. So nasal pharyngeal swabs were
attained from 210 of the 211 women who did not have symptoms of COVID-19, of
these women 29 which equalled 13.7% were positive for SARS-CoV-2 thus 29 out of
the 33 patients who tested positive for SARS-CoV-2 on admission had no
symptomology of COVID-19 at the time of admission, which is scary when you think
about it. 15% of the women walking in in a hotbed had COVID-19 so always a
concern in transmission to the fetus.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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Now, it should be emphasised this was an early test, however what came out of this
test very simply was if you had a blood group or blood type A you had a higher risk
of acquiring COVID-19 than if you are non-blood group A or blood group O had the
lowest risk compared with everybody else.
Long-term exposure to air pollution vs mortality
This should really lead to the idea of toxins damage our body, toxins make us more
inflamed, toxins damage our gut, toxins damage our liver. So coronavirus patients in
areas that had high levels of air pollution before the pandemic were more likely to die
from infection than patients from cleaner parts of the country. Interesting, the
patients living for decades in a country with high levels of particulate matter, 15%
more likely to die from corona. This was data completed over 17 years from more
than 3000 countries. The particles come from fuel combustion, automobiles,
refineries, power plants and of course tobacco smoke.
Obesity
Obesity, let’s pause and realise when we talk to our patients we can help them with
this lifestyle issue called obesity. 29 out of 50 states already have an obesity rate of
over 50%, they project that all states at our current trajectory will have an obesity
rate over 50% by 2030. Obesity is an important predictor of severe corona virus. The
US has one of the highest rates in the world, younger adults especially are at
particular risk. And then the hypothesis is, people who are obese may already have
a compromised respiratory function prior to infection. Abdominal obesity the beer
belly if you will, which is typically more prominent in men can cause compression to
the diaphragm, lungs and chest cavity. In addition, people who are obese have
chronic low grade inflammation and an increase in those circulating proinflammatory
cytokines those cytokines which build your crescendo to the cytokine storm before
you contract the pathogenic virus or the novel virus have the worst outcomes. As we
talked about in the previous webinar the idea of a glass, nothing in the glass
meaning you have no cytokines. When you add enough water eventually the glass
will overflow. That is an evocative depiction I hope of the cytokine storm. However
the water will be fuller if you are obese because you haven’t filled with the water
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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depicting those cytokines and inflammation that you have right now from being
overweight or corpulent you will.
Implication of non-alcoholic fatty liver disease NAFLD in patients with
COVID19
So here we have 202 patients with COVID-19, non-alcoholic fatty liver disease. You
would have never thought however, NAFLD usually occurs from those people who
have not watched their diet. So 50% admission out of that 202, however 75.2% it
went up to that number during the hospitalisation. We all know there’s abundant
ACE2 receptors in the small intestine on the liver. The liver has the largest amount of
macrophages. Once again direct tie gut-liver axis. Gut is the bullseye in your health
and obesity was implicated.
Chest x-ray / COVID-19
It is interesting that a chest x-ray is not very revealing or not very accurate at all. it
was almost 90% normal or mild and it was a substantial number of chest x-rays. So
by the end we are going to have at the end of this webinar a better look-see if you
will into what is a good way to test the patients.
Men
I thought 2 weeks ago men were more susceptible to coronavirus because of
hypertension, because men had more hypertension because of weight - no. The
estrogenic compounds in women have shown to enable them to have a better more
robust immune response to viral challenges than men. Unfortunately in most
instances women usually lose with that estrogenic issue however in this instance
thank you for them that they are able to ward off the viral challenges because of their
estradiol and phytoestrogens.
Immune system
So let’s discuss the idea of immune system. We went into some detail last time but
let’s look at it from a different perspective. There are 3 levels of defence against
disease causing organisms:
1. Barrier - I’m a big proponent of barrier
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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- Skin and mucus
- Of course your gut, stomach acid and digestive enzymes
- And of course once again beneficial bacteria that can live in your colon
2. Innate Immunity: Then we get to our regular immune system, that innate vs
acquired or adaptive. The innate immune system is white blood cells called
neutrophils and macrophages and they engulf and destroy these foreign
invaders.
3. Acquired immunity: Then we get to the adaptive and acquired. And I’m not
going get too granular in here in that white blood cells called T cells target and
destroy infected cells, also B cells and plasma cells produce antibodies. So
the antibodies that we are going to talk about testing are summoned by your
acquired adaptive immune system via B cells.
Foundational immune support
What are we talking about foundational immune support - less make it easy, last time
I gave you a plethora of things to consider now we are going to tighten it up a little
bit:
Lifestyle: Let’s look at our lifestyle.
• Diet: Right now who better, when better than to incorporate a good quality
diet. Your typical culprits you want to remove like gluten, dairy, fried food,
sugar, soy. Diet is a critical element. I can’t tell you how many people in the
last month I’ve talked to have said their wife and their husband or their partner
has never been a better cook. I hope when we come out of this that we realize
that home cooking is a positive statement.
• Sleep: Sleep gives your immune system the opportunity to recover. 7-8 good
hours of sleep. Not only that, sleep also detoxifies your brain.
• Hydration: everybody should stay hydrated, now is a critical time. Half your
body weight in water, adding 8 ounces for every 15 minutes that you exercise.
• Exercise: Segwaying into exercise you are going to see a succeeding slide
that talks about exercise and the positive outcomes it can help lead to from
COVID-19.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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As I’ve said before the two things you are allowed walk out of your house for are
food and exercise. Look how essential exercise is.
Intestinal permeability and microbiota balance: Then for lifestyle, I really want to
let it resonate with everybody that intestinal permeability and microbiota balance is at
the forefront.
• Vitamin C: In addition to that vitamin C. Vitamin C is being used so readily,
what I like about vitamin C is that it helps engage immune system function,
decreases viral growth and reduces symptoms from viral onset.
• Vitamin A: As well as vitamin A, starting at 10,000IUs. Its also is great for the
immune system and will reduce symptoms. It doesn’t necessarily decrease
viral growth.
• Vitamin D3 & K2: outstanding vitamin to consume. Enhances immune
system, decreases viral growth and reduces symptoms.
• NAC / Glutathione: NAC a lot of literature showing that NAC is great for
upper respiratory, NAC leading into glutathione, glutathione the master
antioxidant in that it is able to ameliorate more free radicals than anything else
if you will on the market.
• Zinc: a hidden gem, zinc citrate enhances immune system, decreases viral
growth and reduces symptomology of the virus.
• Selenium: I’ll just skip probiotics for moment, selenium’s importance for
human health has been examined and recognised more recently. One aspect
of interest in selenium is the biggest impact it has on immune system and
against viral infections. Our current understanding that we discuss in
functional nutrition is this mineral is a trace mineral and it is one that we don’t
want to be lacking in.
• Probiotics: And what better than probiotics, 80% of your immune cells are in
your gut. Probiotics allow to populate your gut with the proper fuel and
conversation with your blood, your nervous system and your hormonal
system.
• Exercise: And here’s your exercise, we talked about that before, regular
exercise helps prevent and reduce the severity of ARDS, which is acute
respiratory distress syndrome. A single session of exercise increases
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
8
production of a critical antioxidant extracellular superoxide dismutase. A
decrease in that antioxidant has been seen in acute lung disease. Actually a
decrease in that antioxidant has been seen in several diseases, not only
including lung disease but heart disease and kidney failure and has also been
associated with certain chronic conditions like osteoarthritis.
Anti-viral support
So you see I broke it up a little differently and I’m not giving you as many slides
because we really covered in great detail the power of the different nutrients.
• Quercetin is now really coming to the forefront and quercetin you can get in a
lot of different fruits and vegetables and it has a wide range of benefits
including decreasing viral growth, enhancing the immune system and
reducing symptomology.
• EGCG I’ve got a great study on EGCG in a moment.
• Melatonin my goodness, melatonin helps at the gut level for LPS, it helps
with sleep and it diminishes the cytokine storm 20mg of melatonin.
• PEA is interesting in that it helps nerve function but it is also naturally in every
cell of the body and biological response to inflammatory markers. There’s
been over 350 studies, the bottom line is it works through multiple
mechanisms, it attenuates potentially deadly cytokine storms.
• Alpha lipoic acid I’ll have a slide on that.
• Pomegranate again great for immune function.
• omega 3: And we always seem to forget the power of omega 3 fatty acids for
cell membrane health, anti-inflammatory and the biodiversity of the gut.
The viral and cellular membrane
Let’s take a good look at this. Any virus must enter a cell, replicate and damage the
cell escaping to adjacent cells. For viruses there are 3 enzymes that play a critical
role in the sequence, ACE2, furin and 3CL pro. They all can stimulate so here is
what you have, you have your ACE2 going through your furin - this is going to take a
little while to explain - stimulating the NLRP3 inflammasome. So let’s go through this,
give me about 2 minutes to review it.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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The SARS-CoV-2 infects these alveolar cells through the ACE2 receptor. The
destruction of the epithelial cells and increase of cell permeability leads to the
release of the virus. The SARS activates the innate immune system, macrophages
and other innate immune cells that not only capture the virus but also release a large
number of cytokines and chemokines including interleukin 6. Adaptive immunity is
also activated by antigen presenting cells typically dendrite cells in your gut and in
your lung which are your periscope. T and B cells not only play an antiviral role but
they also directly or indirectly promote the secretion of inflammatory cytokines. In
addition under the stimulation of inflammatory factors, a large number of your
inflammatory exudates enter the alveoli resulting in dyspnea and respiratory failure.
As we talked before this spike tropism protein is very powerful in that it sticks to
these ACE2 receptors, it is a sticky protein.
Inside, the uniqueness or presence of furin enzymes on all cell surfaces cleave and
activate the SARS-CoV-2 in a wide range of tissues and organs. Once again it can
damage all these organs at once and it activates and unleashes the NLRP3
inflammasome initiating a flurry of immune reactions that can result in the cytokine
storm. Tropism of the corona virus leads to this furin cleavage in the spike protein. It
is very interesting, this is not present in SARS-CoV-1 or SARS-CoV. Some of the
testing that we’ll get to you’ll see this distinctive difference. The presence of furins on
almost all the cell surfaces allow a dramatically increased ability to fuse to the host
cells so the spike protein and furin activate sites really isn’t the whole story, what we
left out last time was the CL protease, once they’ve entered the human cells corona
viruses produce damage and spread to other cells by creating an enzyme called the
3CL protease. Although several enzymes may be involved in viral replication and
space, the 3CL protease is the most important one of the corona virus family.
ACE2
So here’s your ACE2 which is your host receptor responsible for mediating. This is a
picture everybody uses, I want to share this picture to depict what is going on. The
ACE2, the gut microbiota and cardiovascular, we don’t have to go through the whole
thing, what you are seeing here is ACE2 is common on the lung, the gut, the heart,
liver and the kidney.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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ACE2 is expressed in the heart. Here is what is most interesting I want to share this,
this was a huge takeaway when I came across it, ACE2 cellular distribution in the
human heart is not clearly illuminated. As we all know pericytes with high expression
of ACE2 act as the target cardiac cell. Perictye injury due to virus is the reason you
get the damage, if people are infected by the virus they have a higher risk of heart
attack, it is not the muscle it is actually the pericytes.
Cytokine storm
So here we go with the cytokine storm. So the cytokine storm is interesting in that
pro-inflammatory cytokines defend hosts from invading pathogens but they are also
capable of driving pathological inflammation. So to shorten up the discussion, most
patients with severe COVID-19 exhibit substantially elevated serum levels and pro-
inflammatory cytokines like IL1b and IL6 as well as some others, IL2, IL8, 17 and the
such. In addition also you’ll see a rise in TNF. All of these are characterised there as
the cytokine storm. Also C-reactive protein and d-dimer may be found to be
abnormally high. High levels of pro-inflammatory cytokines may lead to shock and
tissue damage in the heart, liver and kidney as well as respiratory or multiple organ
failure. They also mediate extensive pulmonary pathology leading to this massive
infiltration of neutrophils and macrophages, diffuse alveolar damage with the
formation of hyaline membranes and diffuse thickening of the alveolar wall. They are
bad dudes.
So here is the anatomy and I put this in so that everybody can review this, I’m not
going to read steps 1, 2, 3 and 4, we kind of did that already but I just wanted
everybody to have a picture-word representation of what is going on. Took it believe
it or not from the Wall Street Journal.
Activation of the NLRP3 inflammasome
Here is the activation of the NLRP3 inflammasome. So you get your PAMPS that
stimulate your Toll-like receptor, your TLR speaks to and stimulate NFkB where you
have this release of interleukin and those two interleukins that are released are IL1b
and IL18, in this (it is not depicted clearly) you also get a lot of mitochondrial fatigue
and that is one of the reasons that people feel so tired.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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Decrease NLRP3 Inflammasome
So, what would I do to decrease the NLRP3 inflammasome:
• EGCG green tea is a great choice.
• Quercetin we love, we covered it.
• Resveratrol
• Curcumin
• Ginger - ginger is a flowering plant that has been used in traditional medicine
throughout history as a means of aiding digestion and supporting immune
function.
• Boswellia also works on the 5 hypoxygenase pathway.
• Aloe vera has also shown to decrease the NLRP3 inflammasome.
• Sulforaphane which comes from cruciferous vegetables.
• Omega 3 fatty acids actually may be one of your first choices, probably your
second now behind EGCG and we are going to get to that study in a
moment. Omega 3s actually block certain endotoxins like LPS from clinging
to TLR4.
• Vitamin D bottom line is the former CDC chief Dr Tom Friedman said corona
virus infection may be reduced by vitamin D.
• Melatonin which we talked about decreasing the cytokine storm. And pro-
resolving mediators, these are what fish oils can convert to. They are
resolvins, protectins and maresins, they allow for the resolution of
inflammation and the homeostasis of the initiation and the resolution of
inflammation. Interesting little science titbit, the resolvents are able to pass
the blood brain barrier and cause micro-environment of the brain decreased
inflammation.
The identification of dietary molecules as therapeutic agents to combat
COVID-19 using molecular docking studies
So here is one that we just found last night that is just unreal. The identification of
dietary molecules as therapeutic agents to combat COVID-19 using molecular
docking studies. They checked docking of seven proteins on SARS-CoV-2, they
used 18 compounds that were compared with 2 FDA drugs. Look at those drugs,
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
12
they are the drugs that everybody is talking about, the EGCG was a lead compound
that fit so well into the binding docks the conclusion was green tea EGCG should be
explored as a drug candidate for the treatment of COVID-19. So by getting on the
binding docks they are not allowing other things to bind, the virus can’t get into the
cell.
Vitamin D receptor inhibits NLRP3
Vitamin D receptor inhibits NLRP3 activation, which is fabulous, it physically binds on
the receptor site.
Mechanisms for innate and adaptive immune responses to vitamin D
Here’s some mechanisms for innate and adaptive immune responses and that is a
big takeaway to vitamin D. We can go through this whole slide and all the different
things but I just want to highlight that the mechanism for innate and adaptive immune
responses, vitamin D should be used all the time. There’s some people who said
vitamin D has some negative effects well don’t take 50,000IUs every day, vitamin D3
with K2 5000-10,000IUs has been shown in multiple studies to modulate your
immune system against respiratory viruses in upper respiratory areas.
Evidence that vitamin D supplementation could reduce risk of influenza on
COVID-19 infections and deaths
Here is a study that just came out on April 2nd, in Nutrients 2020, distinct evidence
that vitamin D could reduce the risk of influenza on COVID19 infections and deaths.
To reduce the risk 10,000 IUs per day of D3 for a few weeks then titrate down to
5000, your goal is to raise the concentration to a level of 40-60ng/mL, I like 60-80.
Here is the conclusion of the study, for treatment of COVID19 higher vitamin D would
be useful.
Melatonin
Well I used this slide before but I put in these red arrows, I really wanted to highlight:
1. If you look in the right corner melatonin actually will enable you to get sleep so
you see what it is doing in the lower right corner.
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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2. Then when you look in the upper right corner it is stopping the release of ROS
and oxidative enzymes so you are not having the release of your free radicals.
3. And in addition it is actually blunting inflammation that is very typical in the
cytokine storm. Look at that red arrow stopping all the interleukins from being
released.
4. In addition melatonin has many functions. There are anti-excitatory actions,
vasomotor, we talked about sleep, antioxidant, anti-inflammatory. The
takeaway here is melatonin decreases inflammatory cell recruitment, it
decreases pro-inflammatory cytokines, it decreases the incidence of acute
lung oxidative injury and it has an antioxidant protective property.
So melatonin should be in everybody’s toolbox to deal with what is going on.
Methylation vs higher cytokine storm
So this was given to me by somebody who is a gene expert, this was in Lupus, but
what they found out was that if you couldn’t methylate you had a higher incidence of
a release of NFkB and a higher cytokine storm. So for those who have never heard
the term methylation, methyl group is CH3. If you want to make a proper copy you
want to be able to methylate. So think about 2 footsteps and taking a picture, proper
copy. Hypomethylating is removing one methyl group you are only taking a picture of
one step. It is not the same replicability, leading to aberrancy. In addition,
hypermethylation would be like adding 3 footprints. Hypomethylation leads you down
a path in this study to increase the release of NFkB and possibly a cytokine storm,
everybody now should start to consider gene tests in people who are more
susceptible. What leads to hypomethylation, single nucleotide polymorphisms,
histamine, cell biologies are out and producing histamine. Things like that.
Over-expression of IL6
A lot going on in this over-expression and its potential negative consequences on the
viral immune response. So understand that current science evidence supports
different scenarios where the balance of IL6 production after viral infection can affect
viral clearance promoting viral persistence and chronic inflammation. Interesting in
that the overexpression of interleukin 6 can damage that granule TH1, TH2. It also in
HEALTH & IMMUNITY: A NATURAL PERSPECTIVE FOR A NEW PARADIGM - PT2
FUNCTIONAL MEDICINE UNIVERSITY | ROBERT SILVERMAN DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, FKTR
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theory with the upregulation of IL6 can increase the virulence and host genetic
background also increasing apoptosis and damaging cytolysis.
Brief introduction of IL6
This is an ad and basically here the takeaway on this study is we are showing the
major functions of IL6, its cell sources, its receptors, its cell targets, and its disease
association. IL6 is an important member of the cytokine network, it plays an essential
role in acute inflammation. It is a multifunctional cytokine which also plays an
important role in human metabolism, autoimmune cell differentiation and cell
treatment and so on and so forth. IL6 being the vast culprit. You can see its disease
association in the 6 points there, you can see its cell target. This is if you will a slide
that we could spend a half hour 45minutes in detailing, you have this please review
this post webinar.
IL6 in severe cases of COVID19
In addition, IL6 in severe cases of COVID19, 9 severe COVID19 patients symptoms
in order: fever, cough, dyspnea, fatigue. So the common comorbidity with the raise in
IL6 was hypertension. IL6 interestingly enough was increased with fever, body
temperature. It was also increased with the expression of C-reactive protein, LDH
and D-Dimer. The conclusion, in March 2020, the dynamic change in IL6 can be
used as a marker for severe COVID19. However, what do we do, what can we do to
inhibit IL6? Well we can stimulate this wonderful antioxidant pathway called the Nrf2.
Stimulate the Nrf2 pathway
What helps stimulate the Nrf2, well let’s take a look at some of these supplements
and lifestyle changes. Again I want the lifestyle changes to now start to resonate with
everybody since we have been home for a while and maybe home for a little bit
longer.
• Fish oil stimulates Nrf2
• Caloric restriction, intermittent fasting, time restricted eating
• Curcumin
• Green tea extract
• Milk thistle
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• Alpha lipoid acid
• Sulforaphane
• Ashwaganda root
• Coffee, of course organic coffee. One little aside to the coffee, remember if it
is not organic coffee it is full of a large amount of pesticides. Organic coffee is
limited as to pesticides.
• One more addition to this, low level laser therapy has shown to really help
stimulate the Nrf2 pathway.
Alpha lipoic acid
Alpha lipoic acid I think it has been overlooked. It is actually a cellular coenzyme, it
works with the water and the fat part of the cell, antioxidant. It increases glutathione
levels and it is shown to attenuate increased susceptibility to human corona virus.
The next big thing ahead vagus nerve
What else would I like to share with you, well I’d like to talk about the vagus nerve I
think the vagus nerve is very much overlooked in that the vagus nerve goes from the
medulla oblongata down through the transverse colon. It is 90% afferent and it
innervates so many different structures in between the medulla oblongata and the
transverse colon. It is on the outside of the transverse colon. And therefore it has to
sense what is going on inside the gut. It does so by sensing the bacteria in the gut
and it also communicates guys are you ready and gals toll-like receptor 4, that’s how
TLR communicates in the gut. Having said that, 90% is afferent because it needs to
be sensory, only 10% efferent.
So just a little review once again of the anatomy:
- The medulla oblongata down through the transverse colon innervating the
neck, thorax, liver, pancreas and intestines. The vagus nerve is sensory and
communicates with the CNS, as we all now know there’s been many
statements about loss of taste and smell actually being a precursor and
diagnostic tool that people are using for corona virus, if you lose your sense of
smell and your taste you have some cranial nerve CNS problems.
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- The vagus nerve also is the captain of the ship of the parasympathetic
nervous system, the rest and digest system.
- It also runs the enteric nervous system, that is why the gut is called your
second brain. The enteric nervous system is the largest accumulation of nerve
cells in the body. It regulates immune response, detecting nutrients and
motility. Therefore the interaction of the enteric nervous system vagus nerve
leads to the bidirectionality between the gut and the brain and the brain and
the gut.
Here is a great picture of the vagus nerve and you see how it innervates everything
and I wish I could circle it is also innervating the lung.
Vagus nerve at the interface of microbiota-gut-brain axis
Low vagal tone, you’ll see a higher incidence of IBS and IBD, a decrease in HCL
secretion, pancreatic enzymes and reduction in bile. Bile is a critical element, it is the
soap to bring specific things in your gut it stimulates something which we will talk
about in a moment the migrating motor complex. So targeting the vagus nerve
through appropriate stimulation would be of interest to restoring the homeostasis
between what I call the 3 way calling, the microbiota-gut-brain axis.
Vagus nerve stimulation – inflammation
When you’re able to stimulate the vagus nerve you will have a dramatic reduction in
inflammation. Stimulating that vagus nerve enables you to have a release of
acetylcholine. Of course we just talked about the reduction in inflammation, improves
outcomes in RA and inhibits cytokine production by 30%.
Vagus nerve stimulation also enhances motor and cognitive recovery, reduces
damage to the blood brain barrier, decreases cerebral edema, and also allows for
neuroprotective effects. Look at vagus nerve’s stimulation effect on the gut,
stimulating the vagus nerve in endotoxin induced tight junction injury [with LPS] so it
had a positive outcome because when this right cervical vagus was stimulated it
ameliorated the damage of the tight junctions. It also inhibited the up regulated
activity of myosin and NFkB. Vagus nerve stimulation in conclusion in this 2013
study, attenuated the disruption of intestinal tight junctions.
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Vagus nerve nutritional support
So here’s your vagus nerve nutritional support. One of the other things I want to say
is the vagus nerve is great because it decreases peripheral inflammation something
we are not looking about. I wanted to expand the mindset when I gave this webinar,
didn’t want it to be just vitamin C, I didn’t want to be just vitamin D. So what do we
want:
• vagally mediated probiotics
• Short chain fatty acids or what I like to call post biotics, butyric acid
• Fibre
• Increase your bile acid flow will increase vagus nerve stimulation
• Omega 3 fatty acids because they increase heart rate variability
• L-citrulline increases HRV
• And of course time restricted eating is a great choice
• Sleep more, you may want to incorporate melatonin in there because it is
great with LPS, it also enables you to sleep more.
• And people have asked me, so I threw a slide in, vagus nerve stimulation I
use a violet light to stimulate the vagus nerve very quickly. Gargling and all
the others is a great method, this is just very quick. I stimulate it with the laser
and then I add the nutritional support to hold the level of tone.
Dr Rob’s Gut Matrix
We saw this slide before, every time I try and tie it back to the gut. So for those who
haven’t seen it before:
Everybody knows what leaky gut is and we’ve all heard that expression of leaky gut.
Our intestinal tract has a percent of our immune cells it is where our macro and
micronutrients are absorbed. Having covered that, understand that the intestinal tract
is made up of the small and large intestine. The small intestine is a misnomer, they
call it small but it is really 90-95% of the length, they call it small because of its
diameter which is one inch in comparison to the large intestine which is 2.5 inches.
In addition it is a single layer epithelial cell whereas the large intestine is a tripe layer
epithelial cell. That small intestine thickness is the thickness of a wet paper towel.
Again when you unravel it the length of a tennis to a basketball court.
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So it should be semipermeable, however when it becomes too permeable from
specifically things like food sensitivities, yeast, fungus, medications, toxins and a
whole plethora of other possible causes including dysbiosis the levelling of good and
bad bacteria which should be to the tune of 85% good, your gut is now too
permeable and undigested food particles, bacteria, yeast, fungus and viruses can
pass your gut into your bloodstream.
75% of your toxins, see the tie in, go from your gut in your bloodstream to your liver.
Liver dysfunction toxic chemical overload, 25% go through the gut to the liver
through the portal vein. You also have a higher incidence of insulin, blood sugar,
prediabetes, obesity and the like. Having a leaky gut if you will damages the tight
junctions, increases your incidence of autoimmunity – thyroid falls in there. In
addition you’ll see more muscular skeletal aches and pains, leaky gut leaky brain,
gut on fire brain on fire, leaky gut leaky lung.
The influence of the microbiota on viral infections
The influence of the microbiota on the viral infections, well your good microbiota has
3 different ways to influence your viral infection outcome:
1. Good bacteria can be very protective because it decreases your
inflammasome response.
2. In addition to that it can have an indirect promotion of health through lymphoid
cell proliferation.
3. Or it can have direct promotion on viruses by using an antiviral immune
response by stimulating a good quality interleukin.
GI tract possible route of viral transmission
Let’s go back we saw these before, 53.4% of the patients that had SARS-CoV-2
RNA in their stool, they were positive for SARS, they were positive for the virus in
their stool. Conversely, 23% of patients tested positive in stool despite testing
negative for the virus in respiratory samples. Now let’s Segway forward and see that
we realise that the GI tract is a possible route of viral transmission, in the bathroom
is one of the ways that people can spread it. And prolonged viral shedding in feces of
paediatric patients with corona virus, essentially the SARS-CoV-2 exhibits in
children’s GI tracts or existed for a longer period of time than the respiratory system.
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Clearance in respiratory tract occurred within 2 weeks after the abatement of fever.
Viral RNA remained detectable in stools longer than 4 weeks. So you have a 2 week
period after respiratory abated fever, everything considers symptomology the
abatement of fever. Here we had 24 COVID19 patients, in those COVID 19 patients
that were discharged, each patient had received 2 consecutive negative throat
swabs and one negative rectal swap. The median viral shedding was 12 days. The
shortest was 4 days the longest was 34 days, another study talked about the median
being 20 days and the longest being 37. So having said all that talking about how the
virus can stay in the gut much longer than symptomology or abatement let’s look at
the gut lung axis which is a bidirectional cross talk that occurs between the gut and
the lung, has been termed the gut lung axis.
Intestinal disturbances have been observed in certain lung diseases which are
shown to be mediated by the gut microbiota and some probiotics have shown
beneficial effects on the lung health in the treatment of respiratory diseases. So it
truly stands to reason that a deeper understanding of the gut microbiota and its role
in respiratory disorders will aid in the design and development of improved treatment
for lung disorders. The gut and lung microflora are clearly linked by nutrition, the
immune system and digestive and respiratory health through mutual communication
linking these very unique integral systems. This is an emerging exciting field of
investigation leading to new ways of thinking about the lung and its disorders.
Gut lung communication
So I find this extremely exciting in that here we have the gut lung communication,
we’ve got the oral pharynx which you’ll get environmental products and bacteria to
affect the gut to the lung and the lung to the gut. Whereas in the blood you’ll see
bacterial fragments, short chain fatty acids and immune cells. And the nerves as we
depicted before signals via vagal nerve afferent invasion.
Pulmonary microbiome in health and critical illness
Now, this is a slide let’s take a real good look at it. Now you are seeing that
translocation of bacteria from the gut increasing your incidence of ARDS acute
respiratory distress syndrome. And also being complicated or combined with oral
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dysbiosis. What a takeaway, the gut’s bacteria adversely effects the lung and you
have a higher incidence of ARDS.
Population based gut microbiome associations with hypertension
So before we get into the gut and hypertension, we are probably going to go over a
few minutes so I thank you for your patience and I am going answer your questions, I
just want to make sure that I gave an action packed informative webinar. So here we
are looking at the gut’s affect on hypertension. So we all know that the gut can be
adversely affected by drugs, food, lifestyle, with a lack of biodiversity can increase
blood pressure profiles. So this gut hypertension it is interesting that 41 patients had
ideal blood pressure, 99 patients had hypertension, 56 patients had pre-
hypertension. Patients with pre or hypertension had a reduction in the bacteria
diversity. Then second phase in this same study scientists transplanted fecal matter
from patients into germ free mice. Mice that received fecal matter from hypertensive
patients then developed hypertension. Researchers conversely also transplanted
feces from mice without hypertension into mice with hypertension, reduction in blood
pressure in mice with hypertension. So what did that say - your bacteria can depict
whether you are going to lose hypertension or gain hypertension depending on the
quality, diversity, and the population of your gut bacteria.
SCFAs – short chain fatty acids
Short chain fatty acids is a direct link from gut to hypertension. Dietary fibre, gut
bacteria produce short chain fatty acids. Bacterial populations patients with higher
blood pressure had lower levels of species that produce short chain fatty acids.
Microbiota – factors
There’s a lot going on in this particular slide but it is a very involving slide in that the
microbiota can be controlled by many factors including diet, physical activity,
genetics and epigenetics. The influence of the gut microbiota on the host may be
partially explained by the generation of short chain fatty acids including acetate
butyrate and propionate and the non-beneficial lactate. These SCFAs acting on cell
surfaces including GPR43 GPR41 and Olfr78 regulate blood pressure whereas the
GPR41 and Olfr78 counter regulate each other. So your microbiota ultimately is
speaking to your body and it is one of the key factors in what your blood pressure is.
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The super 7R action plan
So how do you fix the gut well I didn’t share that with you last time, I’d like to share
that with you today.
1. Reset: The number one thing in my super 7R action plan is you want to reset
your diet, anti-inflammatory, no gluten, no processed food, no dairy, no
nicotine, no artificial sweeteners. Possibly keto, definitely Mediterranean, a
good quality whole food diet that doesn’t have processed foods. Change of
lifestyle start making health a premium point in your life. Exercise, sleep,
hydrate, change your mindset. You don’t have to worry we are going to come
out of this and we are going to be better than we were once we get through it.
All our previous generations have gone through something and they were
better for it as we will.
2. Remove: You want to remove unwanted pathogens. Those pathogens are
like bacteria, viruses and the such. By removing those unwanted pathogens,
we recommend oregano oil for the respiratory, thyme oil to go with it.
Berberine, berberine HCL is a fabulous herb. It is great for your dysbiosis train
wreck patients, remember that berberine b = bowel it removes stuff from the
bowel. In addition I like a lot of garlic at this point. Garlic is shown to your all
natural antibiotic and here’s where I put it for this functional medicine people,
liver detox. Those toxins and pathogens speak back and forth between the
liver and the gut and we’ve always had this conversation gut first or liver first,
let’s do it together here is where we can do a detoxification support.
3. Replace: replace what: digestive enzymes and stomach acid, betaine HCL,
protease, amylase and lipase.
4. Regenerate: repair, heal and seal the damage to the intestinal and mucosal
gut lining. The L-glutamine, okra, NAG, apple pectin, alpha lipoic acid, vitamin
D3, omega 3 fatty acids, are a great choice at this point.
5. Reinoculate: And then we want to reinoculate, reinoculate with what,
probiotics, good quality prebiotics garlic, onions, leek, Jerusalem artichoke. If
you wanted a prebiotic supplement you should consider using XOS,
xylooligosaccharides. That pre feeds the pro. Remember the life of a probiotic
is only about 11 days per se. Dr Bugs will get to me on that because I know
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he is listening. Pre and pro biotic which will ultimately lead to your postbiotic.
Your post biotic is the residue left that is going to determine if you are going to
have a health or bad health signal.
6. Reintroduce certain foods, reintroducing certain foods that you may have
taken out, of course not gluten, dairy and the like, but maybe certain foods
that you are no longer allergic to.
7. Retain: Ultimately you want to retain your health through GI integrity, GI
integrity, good probiotic, omega 3, vitamin D, a multivitamin and quality fruits
and greens drink.
Hypertension susceptibility
So now we can look at some genetic tests. These are just blowing up, people are
interested, you want to know if you have a genetic disposition to injury. So longterm
treatment with ACE inhibitors can cause damage to your body. In these groups they
have a higher taste[?] detection and recognition thresholds. So what I do this is a
cheek swab and in this cheek swab it will tell you if you have specific genes that lead
you down a path that enable you to have hypertensive susceptibility. These are tests
that you can take in your house. So right now every functional medicine, functional
neurologist, functional nutrition practitioner etc., loves the home tests since we can’t
see people in office. Here’s a home test to enable people to see if they have a
genetic predisposition to hypertension. And in addition to certain inflammation - look
at those inflammatory markers, imagine if you have a genetic disposition to
interleukin. So what I did was they knew I was having a webinar so here you can go
to toolbox genomics put in the code DrRob you put that code in they told me for the
webinar and in the future you’ll get a $40 discount on all the genes. So hopefully that
enables you to want to conducer it and I thank toolbox for enabling me to get a
discount for everyone who is attending.
COVID-19 ASSAY
Let’s talk about COVID-19 assay, we did it before. I’ve had two weeks and I’ve had a
100 responses so far in patient and we can talk about that and I’m sure you want to
talk about that in the question section. So COVID-19 here’s the key component,
there’s a lot of labs out there that have to test for COVID-19, the bulk are testing for
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just coronavirus which was previous viruses. We are probably all going to test
positive for that because we’ve been exposed. We want to know if we’ve been
exposed to COVID-19. So the current laboratory diagnostic method is I’m looking for
IgM and IgG.
So what is the difference between IgM and IgG, well for one, antibodies made in
response to viruses persist in the blood acting like sentinels and rouse an immediate
response should the virus try to invade again. The antibodies have unique signatures
we call the different protectors modelled after encountering different viruses so
finding them is a signal of a past contact with a particular virus. It is a distinctive
difference between catching an invader red handed versus going back to the crime
scene and dusting for prints. So let’s talk about the difference between IgM and IgG.
IgM are a class of immunoglobulins that’s composed of this 10 structure pentamer
that is released early in the immune response, it refers to the immunoglobulin M. It is
produced in the early stages, it has no subclasses, it is larger than IgG, it is less
abundant, it is unable to travel through the placenta, it is found in blood and lymph,
and temporary antibodies are replaced by IgG. It provides protection against newly
emerging pathogens in the body and it is responsible for agglutination.
Conversely IgG is a class of immunoglobulins the most abundant type that circulate
in the body, it does refer to immunoglobulin G. It is produced in the late stage of
immune response, it has multiple subclasses, it is smaller than IgM, it is a monomer,
it consists of two antigen binding ells, the most abundant, it does travel through the
placenta from the mother to the child, it is found in all body fluids, it is long lasting, it
is very protective against bacterial and viral functions and it actually activates the
compliment system.
So what you want to do is here’s a graphic representation of understanding the days
of infection. So here we’ve got a typical purple line the shows us SARS-CoV-2 RNA
and the antigen. You are typically asymptomatic to 5.1 days then you typically will
see an onset of symptoms, your body will call its protective mechanisms which are
your immunoglobulins and IgM will become detectable approximately on day 7. IgM
will become detectable and at approximately day 14 IgG will come out. IgG remains
in the blood and provides long term immunity. As there are going to be 4 plausible
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results from this test. You can be negative like me for IgM and IgG, so even though
I’ve been exposed I was not infected. You can also be positive for IgM, negative for
IgG, which would imply that you are in the early stages, so clearly quarantine and
maybe take the PCR test. You could also be IgM positive and IgG positive so you
can see you are in the middle of that 14-21 day period and what you really want to
see is negative IgM and positive IgG which means you have your own vaccine. You
need to be 28 days post regular temperature or abatement of fever to know that you
have the full complement of IgG. It takes a while for IgG to fully cascade. Additionally
be very careful when they’re just doing IgG markers and not IgM and IgG, because a
lot of people again are testing for corona virus. This particular kit, there’s some
updates, I shared with a lot of practitioners many of my patients and many more are
taking the test. Essentially the original go through of the kit was what we’d like to
refer to as sensitivity. The sensitivity in the first go round was 87.3% which meant
that we had less than 13% false positives that number has now increased to 91%. In
the bottom number it is all about the denominator the specificity was 100 it has now
dropped to 99%. So the denominator is still a robust stellar number.
So again I’ll pause for a moment, if you want to get the kit it is available, there’s your
website KBMOdiagnostics.com use the code COVID19/DrRob is my code. The
turnaround time from arriving at the lab is 24-48 hours. Right now it is a serum test,
you should be seeing a finger prick test coming soon. The serum test I know we can
talk about the antibodies in the question and answers, the serum test requires a
phlebotomist to come to your house. We did that so you order the test today you get
it tomorrow the phlebotomist comes on Tuesday you resend it Tuesday to
Wednesday you get the results by Thursday. Again you can bypass the phlebotomist
if and when the finger test does come.
As we get right to the finish line, please keep an eye out my book is coming out
August 2020, it is called Super Highway to Health, 7 Steps to Optimizing the Gut-
Brain Connection. Functional Medicine University said they would support us and I
greatly appreciate Dr. Grisanti. My plug for Dr. Grisanti – he is a very very humble
guy so he brought in this New Yorker and I want to make sure that everybody knows
that enrolment is April 20th. He gave these last two webinars for free with his own
money, and I really want to thank him very much for that. There is not a better online
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learning service than FMU. And if you want to learn more about FMU case studies
ClinicalRounds.com
I always like to end with a quote before we get to the questions, “The mind, once
stretched by a new idea, ever returns to its original dimensions.” Sir Oliver Wendell
Holmes.
If you need to get in touch with me, once again there is my Facebook, Instagram,
there’s my website. And if you are interested in laser and you own one there’s my
mastermind laser Facebook group.
Now without further ado, I can hear Dr. Grisanti, let’s answer any questions you may
have.
[there’s a further 20 minutes question and answer discussion time on the recorded
webinar in the archive, both MP3 audio and MP4 video]