Identifying and managing clients with suspected Lyme disease
igennus
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Aug 02, 2019
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About This Presentation
While Lyme disease is considered to be relatively uncommon in the UK, it is likely that many cases are simply undiagnosed, many of which turn up in our clinics frustrated by conventional approaches to managing their symptoms. Being able to identify clients with suspected Lyme disease is vital, as ma...
Slide Content
Identifying and managing clients
with Lyme disease
Nina Bailey BSc MSc, PhD RNutr
1
with Lyme disease
Nina Bailey BSc MSc, PhD RNutr
1
https://www.theguardian.com/science/2019/jul/31/uk-lyme-disease-cases-may-be-three-times-higher-than-estimated
After analysing the anonymous medical records of 8.4 million people from across the UK, scientists
forecast that the total number of Lyme disease diagnoses in the UK could top 8,000 in 2019,
compared with previous estimates of between 2,000 and 3,000 annual diagnoses.
After analysing the anonymous medical records of 8.4 million people from across the UK, scientists
forecast that the total number of Lyme disease diagnoses in the UK could top 8,000 in 2019,
compared with previous estimates of between 2,000 and 3,000 annual diagnoses.
Lyme statistics
https://www.nhs.uk/news/medical-practice/concern-about-rise-in-uk-lyme-disease-cases/
https://caudwelllymedotnet.files.wordpress.com/2016/01/who-factsheet-lyme-borreliosis-epidemiology.pdf
•An estimated 3,000 people in England and Wales are diagnosed
with Lyme disease each year
•Actual numbers are likely to be much higher
•Diagnosis is challenging as Lyme is often misdiagnosed (e.g. as
CFS/fibromyalgia)
Number of Lyme disease cases
in Europe as reported to WHO
Centralized information system
for infectious Diseases (~3,000
in 1990 – 35,000 in 2010)
https://www.nhs.uk/news/medical-practice/concern-about-rise-in-uk-lyme-disease-cases/
https://caudwelllymedotnet.files.wordpress.com/2016/01/who-factsheet-lyme-borreliosis-epidemiology.pdf
•An estimated 3,000 people in England and Wales are diagnosed
with Lyme disease each year
•Actual numbers are likely to be much higher
•Diagnosis is challenging as Lyme is often misdiagnosed (e.g. as
CFS/fibromyalgia)
Number of Lyme disease cases
in Europe as reported to WHO
Centralized information system
for infectious Diseases (~3,000
in 1990 – 35,000 in 2010)
Cairns V, Wallenhorst C, Rietbrock S, et al Incidence of Lyme disease in the UK: a population-based cohort study BMJ Open 2019;9:e025916.
Incidence rates of Lyme disease per 100000 per year by region,
2010–2012 (incidence rates may vary across different parts of a
region)
Estimated number of
cases of Lyme disease
in each region per
calendar year
Season of diagnosis:
•Spring (March–May) 14.1%
•Summer (June–August) 50.1%
• Autumn (September–November) 28.8%
•Winter (December–February) 7.0%
Incidence rates of Lyme disease per 100000 per year by region,
2010–2012 (incidence rates may vary across different parts of a
region)
Estimated number of
cases of Lyme disease
in each region per
calendar year
Season of diagnosis:
•Spring (March–May) 14.1%
•Summer (June–August) 50.1%
• Autumn (September–November) 28.8%
•Winter (December–February) 7.0%
Why Lyme?
•First identified in 1975 in a group of arthritis patients in
Lyme, Connecticut
•1978 Lyme disease was found to be tick-related
•1981 the bacterium
Borrelia burgdorferi
(B. burgdorferi) was
identified as the main
cause of Lyme disease
•First identified in 1975 in a group of arthritis patients in
Lyme, Connecticut
•1978 Lyme disease was found to be tick-related
•1981 the bacterium
Borrelia burgdorferi
(B. burgdorferi) was
identified as the main
cause of Lyme disease
Tick-borne
•B. burgdorferi species require both an invertebrate vector (ticks of
the Ixodes genus) and a vertebrate host (e.g. humans) to complete
their life cycle
•While Lyme disease originates from a tick bite, the resulting
symptoms arise due to an inflammatory process
•If not treated, the infection can affect multiple organ systems,
including the skin, joints, and the nervous and cardiovascular systems
Unfed 1-week
•B. burgdorferi species require both an invertebrate vector (ticks of
the Ixodes genus) and a vertebrate host (e.g. humans) to complete
their life cycle
•While Lyme disease originates from a tick bite, the resulting
symptoms arise due to an inflammatory process
•If not treated, the infection can affect multiple organ systems,
including the skin, joints, and the nervous and cardiovascular systems
Unfed 1-week
Ticks can be found anywhere with
moist air where they are protected
from drying out - typical habitats
include woods, parks, campsites,
gardens, etc
Known tick bite (especially within past 2
weeks) – bites are painless and the risk
of infection increases the longer the
tick is attached (which can be as long
as 7 days)
Animals also acting as hosts can increase
the risk of human exposure, e.g. pets
Ticks are at their most active in the UK between March and November (but
there is still a risk of ticks biting all year round)
moist air where they are protected
from drying out - typical habitats
include woods, parks, campsites,
gardens, etc
Known tick bite (especially within past 2
weeks) – bites are painless and the risk
of infection increases the longer the
tick is attached (which can be as long
as 7 days)
Animals also acting as hosts can increase
the risk of human exposure, e.g. pets
Ticks are at their most active in the UK between March and November (but
there is still a risk of ticks biting all year round)
B. burgdorferi is a spirochetal (spiral shaped) bacteria, which
allows it to penetrate tissues in a corkscrew fashion leading to
intracellular infection – by evading immune attack for as long as
possible
allows it to penetrate tissues in a corkscrew fashion leading to
intracellular infection – by evading immune attack for as long as
possible
Host Invasion Strategies
•Tick salivary proteins enter the host and exert an
immunosuppressive effect, protecting B. burgdorferi from
immune attack and allowing it to freely enter the circulation
•Outer surface proteins of B. burgdorferi vary in response
to immune attack - both genetic shifts and antigens change mean
it is extremely hard to treat
•Biofilm formation- B. burgdorferi embeds itself within a self-
produced matrix of extracellular polymeric substances
(magnesium dependant )
Aslam B, Nisar MA, Khurshid M, Farooq Salamat MK. Immune escape strategies of borrelia burgdorferi. Future Microbiol. 2017
Oct;12:1219-1237.
•Tick salivary proteins enter the host and exert an
immunosuppressive effect, protecting B. burgdorferi from
immune attack and allowing it to freely enter the circulation
•Outer surface proteins of B. burgdorferi vary in response
to immune attack - both genetic shifts and antigens change mean
it is extremely hard to treat
•Biofilm formation- B. burgdorferi embeds itself within a self-
produced matrix of extracellular polymeric substances
(magnesium dependant )
Aslam B, Nisar MA, Khurshid M, Farooq Salamat MK. Immune escape strategies of borrelia burgdorferi. Future Microbiol. 2017
Oct;12:1219-1237.
Host Invasion Strategies
•B. burgdorferi can enter a state of minimal growth and
division to remain viable, such that when the environment is
more suitable (e.g. antibiotic treatment ends) the bacteria can
begin dividing and growing again
•Converts vitamin D to immunosuppressive calcitriol (1,25-
D) shifting Th1 to Th2 and improving the chance of survival
•Eventually, immune response to B. burgdorferi (and salivary
proteins) occurs, resulting in antibody and proinflammatory
cytokine production
Aslam B, Nisar MA, Khurshid M, Farooq Salamat MK. Immune escape strategies of borrelia burgdorferi. Future Microbiol. 2017
Oct;12:1219-1237.
•B. burgdorferi can enter a state of minimal growth and
division to remain viable, such that when the environment is
more suitable (e.g. antibiotic treatment ends) the bacteria can
begin dividing and growing again
•Converts vitamin D to immunosuppressive calcitriol (1,25-
D) shifting Th1 to Th2 and improving the chance of survival
•Eventually, immune response to B. burgdorferi (and salivary
proteins) occurs, resulting in antibody and proinflammatory
cytokine production
Aslam B, Nisar MA, Khurshid M, Farooq Salamat MK. Immune escape strategies of borrelia burgdorferi. Future Microbiol. 2017
Oct;12:1219-1237.
L-form:
Lack of cell wall makes targeting by immune system and antibiotics more
difficult
Capable of intracellular infection
Converts vitamin D to immunosuppressive calcitriol (1,25-D)
Causes autoimmunity
Cystic form:
B. burgdorferi can convert to a cystic form as a result of antibiotic exposure
Can lie dormant in tissues (including the CNS) for long periods of time,
where it evades immune surveillance
Not mobile = no symptoms
Can convert back to spirochete resulting in relapse (e.g stress induced)
B. burgdorferi employs numerous mechanisms to evade the
immune system and persist despite antibiotic therapy, including
changing its form:
Lack of cell wall makes targeting by immune system and antibiotics more
difficult
Capable of intracellular infection
Converts vitamin D to immunosuppressive calcitriol (1,25-D)
Causes autoimmunity
Cystic form:
B. burgdorferi can convert to a cystic form as a result of antibiotic exposure
Can lie dormant in tissues (including the CNS) for long periods of time,
where it evades immune surveillance
Not mobile = no symptoms
Can convert back to spirochete resulting in relapse (e.g stress induced)
B. burgdorferi employs numerous mechanisms to evade the
immune system and persist despite antibiotic therapy, including
changing its form:
Acute phase
1-3 weeks after infection
Around 70% Lyme disease patients develop the classic bull’s-
eye rash known as erythema migrans
Flu-like symptoms, (especially shortly after being infected)
These include a fever, trouble sleeping, neck pain, fatigue,
chills, sweats and muscle aches
Poor sleep, chronic fatigue and lethargy
Symptoms and severity differs from person to person
People treated with appropriate antibiotics (e.g. doxycycline,
amoxicillin, or cefuroxime) in the early stages can recover
rapidly and completely but this window of opportunity is
limited
Stages of Lyme disease
1-3 weeks after infection
Around 70% Lyme disease patients develop the classic bull’s-
eye rash known as erythema migrans
Flu-like symptoms, (especially shortly after being infected)
These include a fever, trouble sleeping, neck pain, fatigue,
chills, sweats and muscle aches
Poor sleep, chronic fatigue and lethargy
Symptoms and severity differs from person to person
People treated with appropriate antibiotics (e.g. doxycycline,
amoxicillin, or cefuroxime) in the early stages can recover
rapidly and completely but this window of opportunity is
limited
Stages of Lyme disease
Large erythema migrans with a
central clearing and ‘bull’s-eye’
Large erythema migrans with a
central clearing and ‘bull’s-eye’
Small erythema migrans with a
central clearing and ‘bull’s-eye’
https://www.nice.org.uk/guidance/ng95/
central clearing and ‘bull’s-eye’
Large erythema migrans with a
central clearing and ‘bull’s-eye’
Small erythema migrans with a
central clearing and ‘bull’s-eye’
https://www.nice.org.uk/guidance/ng95/
Erythema migrans with no central
clearing or ‘bull’s-eye’
Erythema migrans with no clear
central clearing but clear ‘bull’s-eye’
Erythema migrans with clear central
clearing but no ‘bull’s-eye’
https://www.nice.org.uk/guidance/ng95/
clearing or ‘bull’s-eye’
Erythema migrans with no clear
central clearing but clear ‘bull’s-eye’
Erythema migrans with clear central
clearing but no ‘bull’s-eye’
https://www.nice.org.uk/guidance/ng95/
Chronic phase
Weeks to months after infection
B. burgdorferi begins to enter cells (thus evading the
immune system) giving rise to symptoms that are in addition
to those associated with the acute phase:
digestive issues, including nausea and loss of appetite
mood changes, including increased depression and fatigue
headache and cognitive changes including forgetfulness,
anxiety, brain fog, trouble in concentrating
achiness and joint pains – with some patients going on to
develop symptoms of arthritis
Stages of Lyme disease
Weeks to months after infection
B. burgdorferi begins to enter cells (thus evading the
immune system) giving rise to symptoms that are in addition
to those associated with the acute phase:
digestive issues, including nausea and loss of appetite
mood changes, including increased depression and fatigue
headache and cognitive changes including forgetfulness,
anxiety, brain fog, trouble in concentrating
achiness and joint pains – with some patients going on to
develop symptoms of arthritis
Stages of Lyme disease
Autoimmune phase
Months to years after infection (affects ~15% cases)
Long-term exposure of the host immune system to spirochaetes
and/or borrelial compounds may induce chronic autoimmune
disease
As B. burgdorferi disseminates throughout the body, it can cause
arthritis, carditis, and neurologic deficits
•Lyme neuroborreliosis affects the nervous system
•Lyme carditis affects the heart (e.g. atrioventricular block)
•Lyme arthritis affects the joints
Stages of Lyme disease
The symptoms of Lyme disease are both numerous and diverse –
making diagnosis extremely challenging!
Months to years after infection (affects ~15% cases)
Long-term exposure of the host immune system to spirochaetes
and/or borrelial compounds may induce chronic autoimmune
disease
As B. burgdorferi disseminates throughout the body, it can cause
arthritis, carditis, and neurologic deficits
•Lyme neuroborreliosis affects the nervous system
•Lyme carditis affects the heart (e.g. atrioventricular block)
•Lyme arthritis affects the joints
Stages of Lyme disease
The symptoms of Lyme disease are both numerous and diverse –
making diagnosis extremely challenging!
Laboratory testing – the two-tier algorithm
Do antibiotics always work?
•Meta-analysis of 19 studies (2532 patients) comparing the efficacy and safety of
antibiotic therapy in early Lyme disease - more than 80% of patients showed a
treatment response, 84% at two or fewer months after starting treatment and 80%
at 12 or more months following treatment initiation
•Treatment-related adverse effects occurred in around 31% of people and included
vomiting and diarrhoea as well as a Herxheimer-like reaction (a systemic reaction to
endotoxin-like products released by the death of the bacteria)
•Current antibiotics used to treat Lyme disease are highly active against the growing
spirochetal form of B. burgdorferi but have poor activity against the atypical
persister forms (e.g. cystic, L-form & biofilms)
•These persister forms that are not killed by the current Lyme antibiotics may
underlie the persistent symptoms in patients despite the standard antibiotic
treatment
Torbahn G, Hofmann H, Rücker G et al. Efficacy and safety of antibiotic therapy in early cutaneous lyme borreliosis: a network meta-analysis. JAMA Dermatol.
2018;154(11):1292–1303.
•Meta-analysis of 19 studies (2532 patients) comparing the efficacy and safety of
antibiotic therapy in early Lyme disease - more than 80% of patients showed a
treatment response, 84% at two or fewer months after starting treatment and 80%
at 12 or more months following treatment initiation
•Treatment-related adverse effects occurred in around 31% of people and included
vomiting and diarrhoea as well as a Herxheimer-like reaction (a systemic reaction to
endotoxin-like products released by the death of the bacteria)
•Current antibiotics used to treat Lyme disease are highly active against the growing
spirochetal form of B. burgdorferi but have poor activity against the atypical
persister forms (e.g. cystic, L-form & biofilms)
•These persister forms that are not killed by the current Lyme antibiotics may
underlie the persistent symptoms in patients despite the standard antibiotic
treatment
Torbahn G, Hofmann H, Rücker G et al. Efficacy and safety of antibiotic therapy in early cutaneous lyme borreliosis: a network meta-analysis. JAMA Dermatol.
2018;154(11):1292–1303.
The long-term persistence of symptoms and failure of the
antibiotic therapy are reminiscent of chronic biofilm-associated
infections
Di Domenico EG, Cavallo I, Bordignon V, D'Agosto G, Pontone M, Trento E, Gallo MT, Prignano G, Pimpinelli F, Toma L, Ensoli F. The
Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis. Front Neurol. 2018 Dec 3;9:1048.
antibiotic therapy are reminiscent of chronic biofilm-associated
infections
Di Domenico EG, Cavallo I, Bordignon V, D'Agosto G, Pontone M, Trento E, Gallo MT, Prignano G, Pimpinelli F, Toma L, Ensoli F. The
Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis. Front Neurol. 2018 Dec 3;9:1048.
Nausea
IBS/IBD
Dizziness
Sleep disturbance
Poor concentration
Memory loss
Irritability and mood swings
Depression
Fatigue
Blurred vision and eye pain
Tinnitus
Vertigo
Cranial nerve disturbance (facial
numbness, pain, tingling, palsy or
optic neuritis)
Hot flushes or chills
Night sweats
Sore throat
Swollen glands
Stiff neck
Joint pain or joint stiffness
Arthritis
Myalgia
Chest pain and palpitations
Abdominal pain
Back pain
Jaw pain
Testicular/pelvic pain
Headache/migraine
IBS/IBD
Dizziness
Sleep disturbance
Poor concentration
Memory loss
Irritability and mood swings
Depression
Fatigue
Blurred vision and eye pain
Tinnitus
Vertigo
Cranial nerve disturbance (facial
numbness, pain, tingling, palsy or
optic neuritis)
Hot flushes or chills
Night sweats
Sore throat
Swollen glands
Stiff neck
Joint pain or joint stiffness
Arthritis
Myalgia
Chest pain and palpitations
Abdominal pain
Back pain
Jaw pain
Testicular/pelvic pain
Headache/migraine
Lyme is often misdiagnosed…
–gout
–Reiter’s syndrome, psoriatic arthritis, ankylosing
spondylitis
–rheumatoid arthritis
–depression
–fibromyalgia
–chronic fatigue syndrome
–MS
–gout
–Reiter’s syndrome, psoriatic arthritis, ankylosing
spondylitis
–rheumatoid arthritis
–depression
–fibromyalgia
–chronic fatigue syndrome
–MS
Case history - identifying red flags
•Hobbies - e.g. walking/hiking, gardening
•Holidays - e.g. camping or countryside based
•Clothing type - e.g. are the legs/arms generally exposed
•Pets – e.g. cats or dogs
•Symptom details, duration, location (?)
•Any unusual, unexplained rashes?
•Previous health issues?
•Multiple symptoms that do not respond to conventional
interventions?
•Hobbies - e.g. walking/hiking, gardening
•Holidays - e.g. camping or countryside based
•Clothing type - e.g. are the legs/arms generally exposed
•Pets – e.g. cats or dogs
•Symptom details, duration, location (?)
•Any unusual, unexplained rashes?
•Previous health issues?
•Multiple symptoms that do not respond to conventional
interventions?
Common factors in Lyme
•Potential for immune dysfunction:
–Th2 dominance
–reduced NK-cells
–high Th17
–low Treg
•Increased oxidative stress
•Increased inflammation
•Up-regulation of the kynurenine pathway
•Compromised detoxification
•Antibiotic-induced GI disturbances
•Mitochondrial dysfunction
•Compromised nutrient status
•Potential for immune dysfunction:
–Th2 dominance
–reduced NK-cells
–high Th17
–low Treg
•Increased oxidative stress
•Increased inflammation
•Up-regulation of the kynurenine pathway
•Compromised detoxification
•Antibiotic-induced GI disturbances
•Mitochondrial dysfunction
•Compromised nutrient status
Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol Lett. 2001 Feb 1;76(1):43-8.
Stricker RB, Burrascano J, Winger E. Long term decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease. Ann Agric Environ Med.
2002;9(1):111-3.
•NK-cells act to limit spirochete dissemination - numbers are
lower in Lyme patients compared to controls
•Because NK-cells play a role in the generation of Th1 immune
responses, the additional loss of NK activity might be related
to the presence of a Th2 bias and persistent, chronic infection
•Low NK-cells is associated with more severe and prolonged
arthritis and reduced ability to clear spirochetes from tissues
Early Lyme Th2 bias, late stage Lyme Th1 bias?
The role of Natural Killer cells in Lyme
Stricker RB, Burrascano J, Winger E. Long term decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease. Ann Agric Environ Med.
2002;9(1):111-3.
•NK-cells act to limit spirochete dissemination - numbers are
lower in Lyme patients compared to controls
•Because NK-cells play a role in the generation of Th1 immune
responses, the additional loss of NK activity might be related
to the presence of a Th2 bias and persistent, chronic infection
•Low NK-cells is associated with more severe and prolonged
arthritis and reduced ability to clear spirochetes from tissues
Early Lyme Th2 bias, late stage Lyme Th1 bias?
The role of Natural Killer cells in Lyme
Th17 and Treg
•Patients with Lyme disease often develop pronounced Th17 immune
responses that may help control early infection
•Th17 immune responses are important in the control of extracellular
pathogens, but may also lead to autoimmune responses
•However, late in the disease, excessive Th17 responses may be
disadvantageous by contributing to autoimmune responses driving Lyme-
arthritis
•Lyme arthritis is persistent and sustained in the absence of IL-10
•Lowering Th17 and increasing Treg (increasing IL-10) may be key in late
stage Lyme, e.g. arthritis resolution
Shen S, Shin JJ, Strle K, McHugh G, Li X, Glickstein LJ, Drouin EE, Steere AC. Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-
responsive Lyme arthritis. Arthritis Rheum. 2010 Jul;62(7):2127-37.
Whiteside SK, Snook JP, Ma Y, Sonderegger FL, Fisher C, Petersen C, Zachary JF, Round JL, Williams MA, Weis JJ.
IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis. J Immunol. 2018 Feb 15;200(4):1457-1470.
•Patients with Lyme disease often develop pronounced Th17 immune
responses that may help control early infection
•Th17 immune responses are important in the control of extracellular
pathogens, but may also lead to autoimmune responses
•However, late in the disease, excessive Th17 responses may be
disadvantageous by contributing to autoimmune responses driving Lyme-
arthritis
•Lyme arthritis is persistent and sustained in the absence of IL-10
•Lowering Th17 and increasing Treg (increasing IL-10) may be key in late
stage Lyme, e.g. arthritis resolution
Shen S, Shin JJ, Strle K, McHugh G, Li X, Glickstein LJ, Drouin EE, Steere AC. Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-
responsive Lyme arthritis. Arthritis Rheum. 2010 Jul;62(7):2127-37.
Whiteside SK, Snook JP, Ma Y, Sonderegger FL, Fisher C, Petersen C, Zachary JF, Round JL, Williams MA, Weis JJ.
IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis. J Immunol. 2018 Feb 15;200(4):1457-1470.
Arachidonic acid
COX-1
Constitutive
‘gate-keeping functions’
Homeostatic function
Gastrointestinal tract
Renal tract
Platelet function
Macrophage differentiation
COX-2
Induced
Inflammation
Phospholipid
PLA2
Łuczaj W, Moniuszko A, Rusak M, Zajkowska J, Pancewicz S, Skrzydlewska E. Peroxidative metabolism of arachidonic
acid in the course of Lyme arthritis. Ann Agric Environ Med. 2015;22(3):433-7. doi: 10.5604/12321966.1167708.
Flock, M. R., A. C. Skulas-Ray, et al. (2014). "Effects of supplemental long-chain omega-3 fatty acids and erythrocyte
membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy
adults." Prostaglandins Leukot Essent Fatty Acids 91(4): 161-168.
Inflammation, prostaglandins and Lyme
Plasma PLA2 activity has been demonstrated to be more than 3-
fold higher in Lyme arthritis patients than in healthy subjects
Subjects with Lyme meningitis, Lyme arthritis and antibiotic-
refractory Lyme arthritis have increased levels of
proinflammatory products (e.g. TNFa & LTB4
)
peroxidation
products (e.g. MDA & 8-isoPGF2a)
LOX-1
COX-1
Constitutive
‘gate-keeping functions’
Homeostatic function
Gastrointestinal tract
Renal tract
Platelet function
Macrophage differentiation
COX-2
Induced
Inflammation
Phospholipid
PLA2
Łuczaj W, Moniuszko A, Rusak M, Zajkowska J, Pancewicz S, Skrzydlewska E. Peroxidative metabolism of arachidonic
acid in the course of Lyme arthritis. Ann Agric Environ Med. 2015;22(3):433-7. doi: 10.5604/12321966.1167708.
Flock, M. R., A. C. Skulas-Ray, et al. (2014). "Effects of supplemental long-chain omega-3 fatty acids and erythrocyte
membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy
adults." Prostaglandins Leukot Essent Fatty Acids 91(4): 161-168.
Inflammation, prostaglandins and Lyme
Plasma PLA2 activity has been demonstrated to be more than 3-
fold higher in Lyme arthritis patients than in healthy subjects
Subjects with Lyme meningitis, Lyme arthritis and antibiotic-
refractory Lyme arthritis have increased levels of
proinflammatory products (e.g. TNFa & LTB4
)
peroxidation
products (e.g. MDA & 8-isoPGF2a)
LOX-1
Lipid peroxidation is increased in Lyme
•Non-enzymatic oxidation is caused by
ROS attack of AA, EPA and DHA and
produces a number of potentially
harmful lipid peroxidation products
that fuel inflammatory processes
•Hydroxyhexenals (HHE) are produced from omega-3 EPA & DHA
•Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and the F
2
-isoprostane 15(S)-8-iso-
prostaglandin (8-iso-PGF2α) are the best investigated products of lipid peroxidation and
are derived exclusively from arachidonic acid (AA)
•Lipid peroxidation products, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE)
8−isoPGF2α have been shown to be higher in individuals with Lyme arthritis than
healthy controls
Łuczaj W, Moniuszko A, Rusak M, Pancewicz S, Zajkowska J, Skrzydlewska E. Lipid peroxidation products as potential boindicators of Lyme arthritis. Eur J Clin
Microbiol Infect Dis. 2011 Mar;30(3):415-22.
Łuczaj W, Moniuszko A, Rusak M, Zajkowska J, Pancewicz S, Skrzydlewska E. Peroxidative metabolism of arachidonic acid in the course of Lyme arthritis. Ann
Agric Environ Med. 2015;22(3):433-7.
•Non-enzymatic oxidation is caused by
ROS attack of AA, EPA and DHA and
produces a number of potentially
harmful lipid peroxidation products
that fuel inflammatory processes
•Hydroxyhexenals (HHE) are produced from omega-3 EPA & DHA
•Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and the F
2
-isoprostane 15(S)-8-iso-
prostaglandin (8-iso-PGF2α) are the best investigated products of lipid peroxidation and
are derived exclusively from arachidonic acid (AA)
•Lipid peroxidation products, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE)
8−isoPGF2α have been shown to be higher in individuals with Lyme arthritis than
healthy controls
Łuczaj W, Moniuszko A, Rusak M, Pancewicz S, Zajkowska J, Skrzydlewska E. Lipid peroxidation products as potential boindicators of Lyme arthritis. Eur J Clin
Microbiol Infect Dis. 2011 Mar;30(3):415-22.
Łuczaj W, Moniuszko A, Rusak M, Zajkowska J, Pancewicz S, Skrzydlewska E. Peroxidative metabolism of arachidonic acid in the course of Lyme arthritis. Ann
Agric Environ Med. 2015;22(3):433-7.
Inflammation in Lyme disease
•Increased levels of inflammatory cytokines can induce
/contribute to glutathione depletion, which, in turn, may activate
redox-sensitive transcription factors, such as NF-κB (driving
inflammation by triggering pro-inflammatory cytokine
production)
•Patients with persistent symptoms tend to have high Th1 activity
•High pro-inflammatory cytokine levels (e.g. IL-1β, IL-6 & TNF-α)
are often associated with fatigue-related symptoms in Lyme
(often confusing this with CFS/ME) by up-regulating IDO
Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M.
The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood.
2006 Dec 15;108(13):4118-25.
•Increased levels of inflammatory cytokines can induce
/contribute to glutathione depletion, which, in turn, may activate
redox-sensitive transcription factors, such as NF-κB (driving
inflammation by triggering pro-inflammatory cytokine
production)
•Patients with persistent symptoms tend to have high Th1 activity
•High pro-inflammatory cytokine levels (e.g. IL-1β, IL-6 & TNF-α)
are often associated with fatigue-related symptoms in Lyme
(often confusing this with CFS/ME) by up-regulating IDO
Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M.
The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood.
2006 Dec 15;108(13):4118-25.
Inflammation and oxidative
stress
(IFN-g, TNF-a, IL-1, IL-6 &
cortisol) increase the activity of
the enzyme IDO which catalyses
the oxidation of tryptophan to
N-formylkynurenine, kynurenine
and the downstream QA
Kynurenine
Quinolinic acid
(QA)
NMDA receptor
Tryptophan
Symptoms
Sleep disturbance
Depression
Low libido
Fatigue
Brain fog
Cognitive dysfunction
IDO
The NMDA receptor is important for controlling
synaptic plasticity and memory function.
Magnesium supplementation plays a ‘calming’
role in the regulation of NMDA by acting as a
gatekeeper and preventing overstimulation
Glutamate
(excitatory neurotransmitter)
GABA
(inhibitory neurotransmitter)
Requires vitamin B6 and magnesium
Omega-3 EPA &
ubiquinol can all
reduce the
conversion of
tryptophan to QA
glutamate decarboxylase
Quinolinic acid is significantly elevated in
B. burgdorferi infection and may
contribute to the neurologic and
cognitive deficits seen in
many Lyme disease patients
Halperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology. 1992 Jan;42(1):43-5
stress
(IFN-g, TNF-a, IL-1, IL-6 &
cortisol) increase the activity of
the enzyme IDO which catalyses
the oxidation of tryptophan to
N-formylkynurenine, kynurenine
and the downstream QA
Kynurenine
Quinolinic acid
(QA)
NMDA receptor
Tryptophan
Symptoms
Sleep disturbance
Depression
Low libido
Fatigue
Brain fog
Cognitive dysfunction
IDO
The NMDA receptor is important for controlling
synaptic plasticity and memory function.
Magnesium supplementation plays a ‘calming’
role in the regulation of NMDA by acting as a
gatekeeper and preventing overstimulation
Glutamate
(excitatory neurotransmitter)
GABA
(inhibitory neurotransmitter)
Requires vitamin B6 and magnesium
Omega-3 EPA &
ubiquinol can all
reduce the
conversion of
tryptophan to QA
glutamate decarboxylase
Quinolinic acid is significantly elevated in
B. burgdorferi infection and may
contribute to the neurologic and
cognitive deficits seen in
many Lyme disease patients
Halperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology. 1992 Jan;42(1):43-5
Moniuszko-Malinowska A, Łuczaj W, Jarocka-Karpowicz I, Pancewicz S, Zajkowska J, Andrisic L, Zarkovic N, Skrzydlewska E. Lipid peroxidation in the
pathogenesis of neuroborreliosis. Free Radic Biol Med. 2016 Jul;96:255-63.
Sambri V., Cevenini R. Incorporation of cysteine by Borrelia burgdorferi and Borrelia hermsii. Canadian Journal of Microbiology. 1992;38(10):1016–1021.
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015 Aug;5:66-70.
Glutathione, oxidative stress and Lyme
Glutathione peroxidase is the major enzyme participating in peroxide
decomposition, including lipid peroxides
•B. burgdorferi has been shown to passively absorb its host's cysteine
lowering the levels of glutathione, leading to excess ROS and RNS
•Higher levels of oxidative stress also contributes to depletion of
glutathione
The activity of glutathione peroxidase as well as the level of vitamin E
has been demonstrated in Lyme patients to be decreased by ~25% and
27% respectively, compared to controls
pathogenesis of neuroborreliosis. Free Radic Biol Med. 2016 Jul;96:255-63.
Sambri V., Cevenini R. Incorporation of cysteine by Borrelia burgdorferi and Borrelia hermsii. Canadian Journal of Microbiology. 1992;38(10):1016–1021.
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015 Aug;5:66-70.
Glutathione, oxidative stress and Lyme
Glutathione peroxidase is the major enzyme participating in peroxide
decomposition, including lipid peroxides
•B. burgdorferi has been shown to passively absorb its host's cysteine
lowering the levels of glutathione, leading to excess ROS and RNS
•Higher levels of oxidative stress also contributes to depletion of
glutathione
The activity of glutathione peroxidase as well as the level of vitamin E
has been demonstrated in Lyme patients to be decreased by ~25% and
27% respectively, compared to controls
Lyme: inflammation, oxidative stress and mitochondrial
dysfunction
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015 Aug;5:66-70.
Reduced antioxidant status, (e.g.
glutathione & CoQ10), low
magnesium, increased oxidative
stress can lead to the opening of
mitochondrial permeability
transition pore (mPTP) which
may ultimately contribute to a
condition of mitochondrial
dysfunction observed in some
Lyme patients
dysfunction
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015 Aug;5:66-70.
Reduced antioxidant status, (e.g.
glutathione & CoQ10), low
magnesium, increased oxidative
stress can lead to the opening of
mitochondrial permeability
transition pore (mPTP) which
may ultimately contribute to a
condition of mitochondrial
dysfunction observed in some
Lyme patients
Interventions
Current treatments include
NICE guidance on Lyme disease states that those without focal
symptoms (such as nervous system involvement) should
receive 100mg oral doxycycline twice a day or 200mg once
per day for 21 days.
The first alternative to this is oral amoxicillin, 1g three times
per day for 21 days and the second alternative is oral
azithromycin, 500mg daily for 17 days.
Pain killers (e.g. NSAIDS, COX-2 inhibitors)
Antidepressants (e.g. SSRIs)
NICE guidance on Lyme disease states that those without focal
symptoms (such as nervous system involvement) should
receive 100mg oral doxycycline twice a day or 200mg once
per day for 21 days.
The first alternative to this is oral amoxicillin, 1g three times
per day for 21 days and the second alternative is oral
azithromycin, 500mg daily for 17 days.
Pain killers (e.g. NSAIDS, COX-2 inhibitors)
Antidepressants (e.g. SSRIs)
Antibiotics commonly used for the treatment of Lyme include doxycycline,
amoxicillin or cefuroxime
•Long-term intervention ≥21 days?
•Taking minerals such as calcium, iron, magnesium or zinc at the same time
as antibiotics can decrease the absorption of both the antibiotic and the
mineral, therefore
–antibiotics and minerals should be taken a minimum of 2 hours apart
•Antibiotics may decrease the absorption or increase the elimination of a
number of nutrients, including calcium, magnesium, beta-carotene, folate,
iron, magnesium, potassium and sodium, and vitamins A, B12, D and K
–long-term antibiotic use should be combined with vitamin and mineral
supplementation
amoxicillin or cefuroxime
•Long-term intervention ≥21 days?
•Taking minerals such as calcium, iron, magnesium or zinc at the same time
as antibiotics can decrease the absorption of both the antibiotic and the
mineral, therefore
–antibiotics and minerals should be taken a minimum of 2 hours apart
•Antibiotics may decrease the absorption or increase the elimination of a
number of nutrients, including calcium, magnesium, beta-carotene, folate,
iron, magnesium, potassium and sodium, and vitamins A, B12, D and K
–long-term antibiotic use should be combined with vitamin and mineral
supplementation
Managing potential issues that may arise as a
consequence of the current treatments
•Antibiotics
•Antidepressants
•Pain killers (e.g. NSAIDs)
•Digestive disorders can lead to poor absorption of
nutrients
consequence of the current treatments
•Antibiotics
•Antidepressants
•Pain killers (e.g. NSAIDs)
•Digestive disorders can lead to poor absorption of
nutrients
Improving gut health – improve nutrient absorption
Several probiotic strains such as Lactobacillus Bacteroides thetaiotaomicron,
Bifidobacterium longum and Lactobacillus rhamnosus, Bifidobacterium infantis,
Lactobacillus plantarum shown to have beneficial effects on tight junction - and
intestinal barrier function
Increasing zonula occludens-1 (ZO-1)
Increased transcription of occludin and cingulin genes
Decreased faecal zonulin levels (a marker indicating enhanced gut permeability)
Decreased proinflammatory cytokines
Short-chain non-digestible carbohydrates (inulin-type fructans, fructo-
oligosaccharides (FOS) and galacto-oligosaccharides (GOS)) are the quintessential
prebiotics (occurring naturally in cereals, fruits and vegetables) and the target
bacterial groups are typically Bifidobacterium and Lactobacillus
Fermented foods like sauerkraut, kimchi, yogurt, kefir
L-glutamine, vitamins A & D
Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC Regulation of tight junction permeability by intestinal bacteria and dietary components.
Nutr. 2011 May;141(5):769-76.
Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF
Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J
Int Soc Sports Nutr. 2012 Sep 20;9(1):45.
Several probiotic strains such as Lactobacillus Bacteroides thetaiotaomicron,
Bifidobacterium longum and Lactobacillus rhamnosus, Bifidobacterium infantis,
Lactobacillus plantarum shown to have beneficial effects on tight junction - and
intestinal barrier function
Increasing zonula occludens-1 (ZO-1)
Increased transcription of occludin and cingulin genes
Decreased faecal zonulin levels (a marker indicating enhanced gut permeability)
Decreased proinflammatory cytokines
Short-chain non-digestible carbohydrates (inulin-type fructans, fructo-
oligosaccharides (FOS) and galacto-oligosaccharides (GOS)) are the quintessential
prebiotics (occurring naturally in cereals, fruits and vegetables) and the target
bacterial groups are typically Bifidobacterium and Lactobacillus
Fermented foods like sauerkraut, kimchi, yogurt, kefir
L-glutamine, vitamins A & D
Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC Regulation of tight junction permeability by intestinal bacteria and dietary components.
Nutr. 2011 May;141(5):769-76.
Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF
Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J
Int Soc Sports Nutr. 2012 Sep 20;9(1):45.
Probiotics and omega-3 promote a healthy microbiome,
support immune function and enhance NK-cell activity
Hansen ES, Medić V, Kuo J, Warner TF, Schell RF, Nardelli DT. Interleukin-10 (IL-10) inhibits Borrelia burgdorferi-induced IL-17
production and attenuates IL-17-mediated Lyme arthritis. Infect Immun. 2013 Dec;81(12):4421-30.
support immune function and enhance NK-cell activity
Hansen ES, Medić V, Kuo J, Warner TF, Schell RF, Nardelli DT. Interleukin-10 (IL-10) inhibits Borrelia burgdorferi-induced IL-17
production and attenuates IL-17-mediated Lyme arthritis. Infect Immun. 2013 Dec;81(12):4421-30.
Cysteine depletion is common in Lyme
N-Acetyl –L-cysteine (NAC) has a direct antioxidant capacity and through its promotion of
glutathione synthesis .
•Glutathione is a tri-peptide [L-cysteine, L-glutamine and L-glycine] with L-cysteine the
limiting amino acid.
Why not supplement directly with L-cysteine?
•L-cysteine loses the majority [~85%] of its sulphur groups (the active part of glutathione)
during digestion, while NAC is more stable and only loses ~15%.
•NAC is a biofilm disruptor
For optimum efficacy NAC needs synergists. Alpha lipoic acid, L-glutamine, vitamin C and
vitamin E play an important role in the regeneration of glutathione (vitamin C converts
oxidised glutathione into its reduced form, vitamin E has the same effect on vitamin C).
Wiklund O, Fager G, Andersson A, Lundstam U, Masson P, Hultberg B. N-acetylcysteine treatment lowers plasma homocysteine but not serum
lipoprotein(a) levels. Atherosclerosis. 1996 Jan 5;119(1):99-106.
N-Acetyl –L-cysteine (NAC) has a direct antioxidant capacity and through its promotion of
glutathione synthesis .
•Glutathione is a tri-peptide [L-cysteine, L-glutamine and L-glycine] with L-cysteine the
limiting amino acid.
Why not supplement directly with L-cysteine?
•L-cysteine loses the majority [~85%] of its sulphur groups (the active part of glutathione)
during digestion, while NAC is more stable and only loses ~15%.
•NAC is a biofilm disruptor
For optimum efficacy NAC needs synergists. Alpha lipoic acid, L-glutamine, vitamin C and
vitamin E play an important role in the regeneration of glutathione (vitamin C converts
oxidised glutathione into its reduced form, vitamin E has the same effect on vitamin C).
Wiklund O, Fager G, Andersson A, Lundstam U, Masson P, Hultberg B. N-acetylcysteine treatment lowers plasma homocysteine but not serum
lipoprotein(a) levels. Atherosclerosis. 1996 Jan 5;119(1):99-106.
Antioxidant support
Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates
the expression of a set of antioxidant and detoxifying genes and is a
target for nutritional intervention
Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates
the expression of a set of antioxidant and detoxifying genes and is a
target for nutritional intervention
Gut support
Prebiotics / probiotics, fermented foods & omega-3 (EPA)
•Restoring ‘healthy’ commensal microbiota
•Enhance SCFA-producing microbiota
•Increase NK-cell activity
•Th17/Treg balancing
•Enhancing tight junctions
•Reducing inflammation/oxidative stress
L-glutamine
Bovine colostrum (SigA)
Vitamins A & D3 (SigA)
Prebiotics / probiotics, fermented foods & omega-3 (EPA)
•Restoring ‘healthy’ commensal microbiota
•Enhance SCFA-producing microbiota
•Increase NK-cell activity
•Th17/Treg balancing
•Enhancing tight junctions
•Reducing inflammation/oxidative stress
L-glutamine
Bovine colostrum (SigA)
Vitamins A & D3 (SigA)
Increasing NK-cells
•Beta-glucans
•Enzymatically modified rice bran (EMRB)
•Probiotics
•Vitamins A, C, D & E
•B-vitamins
•Soya isoflavones (e.g. genistein)
•Polyphenols (e.g curcumin & resveratrol)
•Ginseng extract
Ali KH, Melillo AB, Leonard SM, et al. An open-label, randomized clinical trial to assess the immunomodulatory activity of a novel oligosaccharide compound
in healthy adults. Functional Foods in Health and Disease. 2012;2(7):265-79.
Aziz N, Bonavida B. Activation of Natural Killer Cells by Probiotics. For Immunopathol Dis Therap. 2016;7(1-2):41-55.
Grudzien M, Rapak A. Effect of Natural Compounds on NK Cell Activation. J Immunol Res. 2018 Dec 25;2018:4868417.
•Beta-glucans
•Enzymatically modified rice bran (EMRB)
•Probiotics
•Vitamins A, C, D & E
•B-vitamins
•Soya isoflavones (e.g. genistein)
•Polyphenols (e.g curcumin & resveratrol)
•Ginseng extract
Ali KH, Melillo AB, Leonard SM, et al. An open-label, randomized clinical trial to assess the immunomodulatory activity of a novel oligosaccharide compound
in healthy adults. Functional Foods in Health and Disease. 2012;2(7):265-79.
Aziz N, Bonavida B. Activation of Natural Killer Cells by Probiotics. For Immunopathol Dis Therap. 2016;7(1-2):41-55.
Grudzien M, Rapak A. Effect of Natural Compounds on NK Cell Activation. J Immunol Res. 2018 Dec 25;2018:4868417.
Arachidonic acid
COX-1
Constitutive
‘gate-keeping
functions’
Homeostatic function
Gastrointestinal tract
Renal tract
Platelet function
Macrophage differentiation
Induced
Inflammation
Phospholipid
PLA2
COX-2
Both phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2)
are over-expressed in certain disease states and targets
for intervention (Kumar et al. 2013)
The importance of compounds derived from arachidonic acid
(AA) in inflammatory-driven disease is evident from the
range of pharmaceutical products that target the actions of
AA, such as:
•Non-steroidal anti-inflammatory drugs
(NSAIDs such as aspirin & ibuprofen)
•Leukotriene antagonists (e.g. montelukast,
zafirlukast)
•COX-2 inhibitors (e.g. rofecoxib, celecoxib)
The inhibitory effects of eicosapentaenoic acid (EPA) on PLA2 and COX-2 results in decreased AA
availability and decreased AA metabolism, respectively
Omega-3 polyunsaturated fatty acids and inflammatory
processes: nutrition or pharmacology?
Kumar N, Drabu s, Mondal SC. NSAID’s and selectively COX-2 inhibitors as potential chemoprotective agents against cancer: 1st Cancer Update. Arabian
Journal of Chemistry. 2013 6: 1–23
COX-1
Constitutive
‘gate-keeping
functions’
Homeostatic function
Gastrointestinal tract
Renal tract
Platelet function
Macrophage differentiation
Induced
Inflammation
Phospholipid
PLA2
COX-2
Both phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2)
are over-expressed in certain disease states and targets
for intervention (Kumar et al. 2013)
The importance of compounds derived from arachidonic acid
(AA) in inflammatory-driven disease is evident from the
range of pharmaceutical products that target the actions of
AA, such as:
•Non-steroidal anti-inflammatory drugs
(NSAIDs such as aspirin & ibuprofen)
•Leukotriene antagonists (e.g. montelukast,
zafirlukast)
•COX-2 inhibitors (e.g. rofecoxib, celecoxib)
The inhibitory effects of eicosapentaenoic acid (EPA) on PLA2 and COX-2 results in decreased AA
availability and decreased AA metabolism, respectively
Omega-3 polyunsaturated fatty acids and inflammatory
processes: nutrition or pharmacology?
Kumar N, Drabu s, Mondal SC. NSAID’s and selectively COX-2 inhibitors as potential chemoprotective agents against cancer: 1st Cancer Update. Arabian
Journal of Chemistry. 2013 6: 1–23
Vojdani A, Hebroni F, Raphael Y, Erde J, Raxlen B. Novel Diagnosis of Lyme Disease: Potential for CAM Intervention. Evid Based
Complement Alternat Med. 2009 Sep;6(3):283-95.
Complement Alternat Med. 2009 Sep;6(3):283-95.
Biofilm disruptors
•N-acetylcysteine (NAC). In addition to being a precursor to glutathione and an
antioxidant, NAC has been demonstrated to be highly efficient at breaking down
biofilms
•Probiotics
•Antimicrobial plants (e.g. berberine, citrus seed extract, echinacea, golden seal &
oregano oil)
Dinicola S, De Grazia S, Carlomagno G, Pintucci JP. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med
Pharmacol Sci. 2014 Oct;18(19):2942-8. Review.
Roy R, Tiwari M, Donelli G, Tiwari V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence.
2018 Jan 1;9(1):522-554.
Miyazaki Y, Kamiya S, Hanawa T, Fukuda M, Kawakami H, Takahashi H, Yokota H. Effect of probiotic bacterial strains of Lactobacillus, Bifidobacterium, and
Enterococcus on enteroaggregative Escherichia coli. J Infect Chemother. 2010 Feb;16(1):10-8.
Černáková L, Light C, Salehi B, Rogel-Castillo C, Victoriano M, Martorell M, Sharifi-Rad J, Martins N, Rodrigues CF. Novel Therapies for Biofilm-Based Candida
spp. Infections. Adv Exp Med Biol. 2019 Jul 19.
•N-acetylcysteine (NAC). In addition to being a precursor to glutathione and an
antioxidant, NAC has been demonstrated to be highly efficient at breaking down
biofilms
•Probiotics
•Antimicrobial plants (e.g. berberine, citrus seed extract, echinacea, golden seal &
oregano oil)
Dinicola S, De Grazia S, Carlomagno G, Pintucci JP. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med
Pharmacol Sci. 2014 Oct;18(19):2942-8. Review.
Roy R, Tiwari M, Donelli G, Tiwari V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence.
2018 Jan 1;9(1):522-554.
Miyazaki Y, Kamiya S, Hanawa T, Fukuda M, Kawakami H, Takahashi H, Yokota H. Effect of probiotic bacterial strains of Lactobacillus, Bifidobacterium, and
Enterococcus on enteroaggregative Escherichia coli. J Infect Chemother. 2010 Feb;16(1):10-8.
Černáková L, Light C, Salehi B, Rogel-Castillo C, Victoriano M, Martorell M, Sharifi-Rad J, Martins N, Rodrigues CF. Novel Therapies for Biofilm-Based Candida
spp. Infections. Adv Exp Med Biol. 2019 Jul 19.
Plants with anti-borrelia efficacy
Antimicrobial agents derived from natural sources such as plants, herbs,
spices, fruits and essential oils, have shown activity against active and latent
forms of B. burgdorferi
•Dipsacus sylvestris (Wild Teasel)
•Grapefruit seed extract – spirochetes and cysts
•Uncaria tomentosa (Cat’s Claw)
•Otoba parvifolia (Otoba Bark)
•Stevia rebaudiana – spirochetes, cysts & biofilms
Liebold T, Straubinger RK, Rauwald HW. Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds. roots against Borrelia
burgdorferi s. s. in vitro. Pharmazie. 2011 Aug;66(8):628-30.
Brorson O, Brorson SH. Grapefruit seed extract is a powerful in vitro agent against motile and cystic forms of Borrelia burgdorferi sensu lato.
Infection. 2007 Jun;35(3):206-8. No abstract available.
Datar A., Kaur N., Patel S., Luecke D., Sapi E. In vitro effectiveness of samento and banderol herbal extracts on the different morphological
forms of Borrelia burgdorferi. Townsend Lett 2010 7: 1–4.
Antimicrobial agents derived from natural sources such as plants, herbs,
spices, fruits and essential oils, have shown activity against active and latent
forms of B. burgdorferi
•Dipsacus sylvestris (Wild Teasel)
•Grapefruit seed extract – spirochetes and cysts
•Uncaria tomentosa (Cat’s Claw)
•Otoba parvifolia (Otoba Bark)
•Stevia rebaudiana – spirochetes, cysts & biofilms
Liebold T, Straubinger RK, Rauwald HW. Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds. roots against Borrelia
burgdorferi s. s. in vitro. Pharmazie. 2011 Aug;66(8):628-30.
Brorson O, Brorson SH. Grapefruit seed extract is a powerful in vitro agent against motile and cystic forms of Borrelia burgdorferi sensu lato.
Infection. 2007 Jun;35(3):206-8. No abstract available.
Datar A., Kaur N., Patel S., Luecke D., Sapi E. In vitro effectiveness of samento and banderol herbal extracts on the different morphological
forms of Borrelia burgdorferi. Townsend Lett 2010 7: 1–4.
Combinations of phytochemicals provide synergistic benefits
Luteolin (found in broccoli, pepper, thyme, and celery)
Rosmarinic acid (found in Perilla Oil and Rosemary)
Baicalein (Chinese Huang Qin)
Monolaurin (lauric acid derived from coconut)
Vitamin C
Vitamin D3
Iodine
Combining antibiotics with flavones and micronutrients may
enhance efficacy of antibiotics
Goc A, Niedzwiecki A, Rath M. Reciprocal cooperation of phytochemicals and micronutrients typical and atypical forms of borrelia sp. J
Appl Microbiol. 2017 Sep;123(3):637-650
Goc A, Niedzwiecki A, Rath M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia
burgdorferi and Borrelia garinii. J Appl Microbiol. 2015 Dec;119(6):1561-72.
Luteolin (found in broccoli, pepper, thyme, and celery)
Rosmarinic acid (found in Perilla Oil and Rosemary)
Baicalein (Chinese Huang Qin)
Monolaurin (lauric acid derived from coconut)
Vitamin C
Vitamin D3
Iodine
Combining antibiotics with flavones and micronutrients may
enhance efficacy of antibiotics
Goc A, Niedzwiecki A, Rath M. Reciprocal cooperation of phytochemicals and micronutrients typical and atypical forms of borrelia sp. J
Appl Microbiol. 2017 Sep;123(3):637-650
Goc A, Niedzwiecki A, Rath M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia
burgdorferi and Borrelia garinii. J Appl Microbiol. 2015 Dec;119(6):1561-72.
Kynurenine
Quinolinic acid
Tryptophan
IDO
Target IDO and down-regulate quinolinic acid
production
Curcumin: a potent anti-inflammatory (e.g.
down-regulates NF-KB & increases
endogenously made antioxidant)
Omega-3 EPA – reduces IDO and cortisol
Butyrate – increase SCFA-producing flora
Reduce inflammation (e.g. antioxidants and
support endogenously made antioxidants)
Quinolinic acid
Tryptophan
IDO
Target IDO and down-regulate quinolinic acid
production
Curcumin: a potent anti-inflammatory (e.g.
down-regulates NF-KB & increases
endogenously made antioxidant)
Omega-3 EPA – reduces IDO and cortisol
Butyrate – increase SCFA-producing flora
Reduce inflammation (e.g. antioxidants and
support endogenously made antioxidants)
Supporting energy
Magnesium – cofactor for ATP Low magnesium status is common to both
sufferers of Lyme disease (yet required by Borrelia burgdorferi to make
biofilms) and patients with CFS/ME, perpetuating symptoms of fatigue,
often associated with mitochondrial failure
CoQ10/ubiquinol – antioxidant & component of the electron transfer
chain protects cells from the damaging effects of oxidative damage
caused from increased IDO, further reducing the actions of IDO
Magnesium – cofactor for ATP Low magnesium status is common to both
sufferers of Lyme disease (yet required by Borrelia burgdorferi to make
biofilms) and patients with CFS/ME, perpetuating symptoms of fatigue,
often associated with mitochondrial failure
CoQ10/ubiquinol – antioxidant & component of the electron transfer
chain protects cells from the damaging effects of oxidative damage
caused from increased IDO, further reducing the actions of IDO
Additional key nutrients that can help support mitochondrial
function and improve energy include: D-ribose, acetyl -L-
carnitine, lipoic acid and N-acetyl-L-cysteine (NAC)
Consider methylated B-Complex or multivitamin & minerals
Support coenzymes involved in acetyl-CoA production:
•Thiamine pyrophosphate (derived from thiamine)
• Nicotinamide adenine dinucleotide (NAD+ [derived from
niacin])
• Flavin adenine dinucleotide (FAD [derived from riboflavin])
• Lipoic acid
• Coenzyme A (derived from pantothenic acid)
function and improve energy include: D-ribose, acetyl -L-
carnitine, lipoic acid and N-acetyl-L-cysteine (NAC)
Consider methylated B-Complex or multivitamin & minerals
Support coenzymes involved in acetyl-CoA production:
•Thiamine pyrophosphate (derived from thiamine)
• Nicotinamide adenine dinucleotide (NAD+ [derived from
niacin])
• Flavin adenine dinucleotide (FAD [derived from riboflavin])
• Lipoic acid
• Coenzyme A (derived from pantothenic acid)
Nutritional information Per dose % RI*
Vitamin C (ascorbic acid) 240 mg 300
Vitamin B3 (nicotinamide) 48 mg NE 300
Zinc citrate 20 mg 200
Vitamin B5 (pantothenic acid) 18 mg 300
Vitamin B6 (pyridoxal-5-phosphate) 8 mg 570
Iron (ferrous bisglycinate chelate) 7 mg 50
Vitamin B1 (thiamine HCl) 5.5 mg 500
Vitamin B2 (riboflavin-5-phosphate) 4.2 mg 300
Vitamin E (D-alpha tocopherol [natural])2 mg a-TE 16.6
Boron (disodium tetraborate) 2 mg n/a
Manganese bisglycinate 2 mg 100
Copper bisglycinate 1 mg 100
Vitamin A (beta carotene) 800 mg 100
Folate ([6S]-5-methyltetrahydrofolate) 200 mg 100
Selenomethionine 110 mg 200
Iodine (kelp) 150 mg 100
Vitamin B7 (biotin) 100 mg 200
Chromium picolinate 50 mg 125
Molybdenum 50 mg 100
Vitamin K2 (menaquinone) 37.5 mg 50
Vitamin B12 (methylcobalamin) 20 mg 800
Vitamin D3 (cholecalciferol) 10 mg (400 iu) 200
Provides 22 key essential vitamins & minerals in superior body-ready and active forms
for enhanced absorption and utilisation. Our sustained slow-release system optimises
blood nutrient levels for longer-lasting action.
*Reference Intake; Quatrefolic® is a registered trademark owned by Gnosis S.p.A.
Vitamin C (ascorbic acid) 240 mg 300
Vitamin B3 (nicotinamide) 48 mg NE 300
Zinc citrate 20 mg 200
Vitamin B5 (pantothenic acid) 18 mg 300
Vitamin B6 (pyridoxal-5-phosphate) 8 mg 570
Iron (ferrous bisglycinate chelate) 7 mg 50
Vitamin B1 (thiamine HCl) 5.5 mg 500
Vitamin B2 (riboflavin-5-phosphate) 4.2 mg 300
Vitamin E (D-alpha tocopherol [natural])2 mg a-TE 16.6
Boron (disodium tetraborate) 2 mg n/a
Manganese bisglycinate 2 mg 100
Copper bisglycinate 1 mg 100
Vitamin A (beta carotene) 800 mg 100
Folate ([6S]-5-methyltetrahydrofolate) 200 mg 100
Selenomethionine 110 mg 200
Iodine (kelp) 150 mg 100
Vitamin B7 (biotin) 100 mg 200
Chromium picolinate 50 mg 125
Molybdenum 50 mg 100
Vitamin K2 (menaquinone) 37.5 mg 50
Vitamin B12 (methylcobalamin) 20 mg 800
Vitamin D3 (cholecalciferol) 10 mg (400 iu) 200
Provides 22 key essential vitamins & minerals in superior body-ready and active forms
for enhanced absorption and utilisation. Our sustained slow-release system optimises
blood nutrient levels for longer-lasting action.
*Reference Intake; Quatrefolic® is a registered trademark owned by Gnosis S.p.A.
Nutritional information Per dose% RI*
Vitamin C (ascorbic acid) 160 mg 200
Vitamin B3 (niacin) 48 mg 300
Vitamin B5 (pantothenic acid) 36 mg 600
Vitamin B1 (thiamine) 20 mg 1818
Vitamin B6 (pyridoxal-5-phosphate) 20 mg 1429
Vitamin B2 (riboflavin-5-phosphate) 14 mg 1000
Vitamin B12 (methylcobalamin) 900 mg 36000
Folate ([6S]-5-methyltetrahydrofolate) 400 mg 200
Vitamin B7 (biotin) 300 mg 600
*Reference Intake; Quatrefolic® is a registered trademark owned by Gnosis S.p.A.
Methylation support
BIOAVAILABLE FORMS: Super B-Complex delivers maximum levels of key nutrients:
Quatrefolic® provides the body-ready form of folate, as [6S]-5-methyltetrahydrofolate,
the active form of riboflavin, riboflavin-5-phosphate
vitamin B6 as pyridoxal-5-phosphate with cofactor activity
vitamin B12 as methylcobalamin, for enhanced uptake
HIGH DOSE B6, B12 & folate support efficient homocysteine metabolism and methylation pathways,
for heart health & brain function
SPLIT DOSE FOR ENHANCED ABSORPTION: vitamin B12 uptake is optimised by dosing twice daily,
morning & evening
SUSTAINED RELEASE: offers longer-lasting action
Vitamin C (ascorbic acid) 160 mg 200
Vitamin B3 (niacin) 48 mg 300
Vitamin B5 (pantothenic acid) 36 mg 600
Vitamin B1 (thiamine) 20 mg 1818
Vitamin B6 (pyridoxal-5-phosphate) 20 mg 1429
Vitamin B2 (riboflavin-5-phosphate) 14 mg 1000
Vitamin B12 (methylcobalamin) 900 mg 36000
Folate ([6S]-5-methyltetrahydrofolate) 400 mg 200
Vitamin B7 (biotin) 300 mg 600
*Reference Intake; Quatrefolic® is a registered trademark owned by Gnosis S.p.A.
Methylation support
BIOAVAILABLE FORMS: Super B-Complex delivers maximum levels of key nutrients:
Quatrefolic® provides the body-ready form of folate, as [6S]-5-methyltetrahydrofolate,
the active form of riboflavin, riboflavin-5-phosphate
vitamin B6 as pyridoxal-5-phosphate with cofactor activity
vitamin B12 as methylcobalamin, for enhanced uptake
HIGH DOSE B6, B12 & folate support efficient homocysteine metabolism and methylation pathways,
for heart health & brain function
SPLIT DOSE FOR ENHANCED ABSORPTION: vitamin B12 uptake is optimised by dosing twice daily,
morning & evening
SUSTAINED RELEASE: offers longer-lasting action
Serving size: 3 capsules Per serving% RI*
Magnesium citrate
- of which magnesium
Magnesium taurate
- of which magnesium
Magnesium bisglycinate
- of which magnesium
Total elemental magnesium**
903 mg
105 mg
540 mg
45 mg
450 mg
45 mg
195 mg
52%
NUTRITIONAL INFORMATION
* % Reference Intake **(from 1893 mg
magnesium citrate, taurate & bisglycinate)
ADVANCED TRIPLE MAGNESIUM BLEND
FULLY REACTED FORMULA
SPLIT DOSE FORMULA
MULTIPLE HEALTH BENEFITS: magnesium supports
normal energy release, muscle function,
electrolyte balance, nervous system function and
normal psychological function.
Magnesium citrate
- of which magnesium
Magnesium taurate
- of which magnesium
Magnesium bisglycinate
- of which magnesium
Total elemental magnesium**
903 mg
105 mg
540 mg
45 mg
450 mg
45 mg
195 mg
52%
NUTRITIONAL INFORMATION
* % Reference Intake **(from 1893 mg
magnesium citrate, taurate & bisglycinate)
ADVANCED TRIPLE MAGNESIUM BLEND
FULLY REACTED FORMULA
SPLIT DOSE FORMULA
MULTIPLE HEALTH BENEFITS: magnesium supports
normal energy release, muscle function,
electrolyte balance, nervous system function and
normal psychological function.
INGREDIENTS:
Cold-pressed extra-virgin olive oil; AstaPure® from Haematococcus
pluvialis (H.pluvialis) microalgae (10% astaxanthin); capsule shell
(emulsifier: glycerol; modified corn starch, carrageenan, Orange Ovation A,
sodium carbonate)
Astaxanthin’s ROS-scavenging capacity has been shown to be 6000x more than vitamin
C, 800x more than coenzyme Q10, 550x more than vitamin E, 200x more than
polyphenols, 150x more than anthocyanins, and 75x more than alpha lipoic acid - the
majority of the research to date used between 2 mg and 24 mg of astaxanthin daily
Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection
system. Carotenoid Science. 2007;11(6):16–20.
Nutritional information Per capsule
AstaPure® Haematococcus pluvialis
microalgae (10% astaxanthin complex)
42 mg
of which astaxanthin 4 mg
of which lutein 36 mg
of which canthaxanthin 20 mg
of which zeaxanthin 3 mg
of which violaxanthin 0.5 mg
Cold-pressed extra-virgin olive oil; AstaPure® from Haematococcus
pluvialis (H.pluvialis) microalgae (10% astaxanthin); capsule shell
(emulsifier: glycerol; modified corn starch, carrageenan, Orange Ovation A,
sodium carbonate)
Astaxanthin’s ROS-scavenging capacity has been shown to be 6000x more than vitamin
C, 800x more than coenzyme Q10, 550x more than vitamin E, 200x more than
polyphenols, 150x more than anthocyanins, and 75x more than alpha lipoic acid - the
majority of the research to date used between 2 mg and 24 mg of astaxanthin daily
Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection
system. Carotenoid Science. 2007;11(6):16–20.
Nutritional information Per capsule
AstaPure® Haematococcus pluvialis
microalgae (10% astaxanthin complex)
42 mg
of which astaxanthin 4 mg
of which lutein 36 mg
of which canthaxanthin 20 mg
of which zeaxanthin 3 mg
of which violaxanthin 0.5 mg
INGREDIENTS:
Longvida® optimised curcumin extract; capsule shell (emulsifier:
hydroxypropyl methylcellulose); stearic acid; soy lecithin;
maltodextrin; ascorbyl palmitate; silicon dioxide.
LONGVIDA HIGH ABSORPTION FORMULA DELIVERS FREE
FORM CURCUMIN: Longvida
®
is the only delivery system proven to deliver free
form curcumin into the bloodstream and target tissues (all other supplements are
converted to curcumin metabolites after being taken up by the liver and subject to
enzyme conversion - conjugation and glucuronidation)
285x GREATER BIOAVAILABILITY
SINGLE EFFECTIVE 500MG DOSE ACHIEVES CLINICALLY ACTIVE PLASMA LEVELS
Curcumin
Serving size: 1 capsule Per serving
Longvida
®
optimised curcumin extract from
turmeric root (min. 23% curcuminoids)
160 mg
Longvida® optimised curcumin extract; capsule shell (emulsifier:
hydroxypropyl methylcellulose); stearic acid; soy lecithin;
maltodextrin; ascorbyl palmitate; silicon dioxide.
LONGVIDA HIGH ABSORPTION FORMULA DELIVERS FREE
FORM CURCUMIN: Longvida
®
is the only delivery system proven to deliver free
form curcumin into the bloodstream and target tissues (all other supplements are
converted to curcumin metabolites after being taken up by the liver and subject to
enzyme conversion - conjugation and glucuronidation)
285x GREATER BIOAVAILABILITY
SINGLE EFFECTIVE 500MG DOSE ACHIEVES CLINICALLY ACTIVE PLASMA LEVELS
Curcumin
Serving size: 1 capsule Per serving
Longvida
®
optimised curcumin extract from
turmeric root (min. 23% curcuminoids)
160 mg
VESIsorb
TM
Oil-based
Time (hours)
VESIsorb®
Therapeutic level
VESIsorb® delivered CoQ10 is absorbed
FASTER, reaching concentrations that are
STRONGER and stays in the body
LONGER than generic delivery methods
Fully reduced form of CoQ10
VESIsorb® technology for enhanced
bioavailability and tissue distribution
100 mg therapeutic dose
Oil-based
C
max
T
max
TM
Oil-based
Time (hours)
VESIsorb®
Therapeutic level
VESIsorb® delivered CoQ10 is absorbed
FASTER, reaching concentrations that are
STRONGER and stays in the body
LONGER than generic delivery methods
Fully reduced form of CoQ10
VESIsorb® technology for enhanced
bioavailability and tissue distribution
100 mg therapeutic dose
Oil-based
C
max
T
max
‘RESTORE’
pure EPA
‘MAINTAIN’
EPA, DHA and GLA
Minimum 3-6 months
AA to EPA ratio
Inflammatory regulation
Symptoms of inflammatory illness
Optimum brain, cell, heart, immune
and CNS function
Optimum wellbeing
Omega-3 index
AA to EPA ratio
Long-term general and cellular health
Heart, brain and eye health
Reduce risk of chronic illness and help
protect against inflammatory disease
Therapeutic role of Pharmepa®
RESTORE & MAINTAIN™
pure EPA
‘MAINTAIN’
EPA, DHA and GLA
Minimum 3-6 months
AA to EPA ratio
Inflammatory regulation
Symptoms of inflammatory illness
Optimum brain, cell, heart, immune
and CNS function
Optimum wellbeing
Omega-3 index
AA to EPA ratio
Long-term general and cellular health
Heart, brain and eye health
Reduce risk of chronic illness and help
protect against inflammatory disease
Therapeutic role of Pharmepa®
RESTORE & MAINTAIN™
Summary
Advise testing/antibiotics if a client is suspected to
have Lyme
Gut protocol
Immune support (e.g. NK-cells, Th17/Treg
balancing)
Restore healthy tryptophan/kynurenine signalling
Support detoxification
Reduce inflammation/oxidative stress
Advise testing/antibiotics if a client is suspected to
have Lyme
Gut protocol
Immune support (e.g. NK-cells, Th17/Treg
balancing)
Restore healthy tryptophan/kynurenine signalling
Support detoxification
Reduce inflammation/oxidative stress
Categories
HealthcareDownload
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