12. IMMUNE SYSTEM HEALTH Flashcards
(116 cards)
1
Q
What is the immune system and its main purpose?
A
The immune system is a sophisticated system of surveillance, that can identify and neutralise potential threats, and repair resulting damage. It also identifies and neutralises damaged ‘self’ cells e.g., cancer.
It needs to be effective, proportionate and precise - too little and it may compromise health / survival, too much or poorly targeted, may result in chronic inflammation, allergy or autoimmunity.
2
Q
Name FIVE roles of the immune system
A
- Identify and neutralise pathogens
- Distinguish self vs non-self antigens
- Distinguish pathological vs. non-harmful antigens
- Repair the site of any injury or damage
- Tumour surveillance
3
Q
Name FIVE implications of immune system dysfunction
A
- An increased susceptibility to infection (re-activated viruses - shingles)
- Increased susceptibility to autoimmunity (Hashimoto’s thyroiditis, RA, IBD, T1D)
- Allergies and food intolerances
- Insufficient - incomplete repair, scarring. Excessive - cell damage, chronic inflammation
- An inability to effectively recognise and kill abnormal cancer cells.
4
Q
Why do some people become unwell and others don’t despite the same pathogen exposure? What is a key factor in resilience against infection?
A
Pathogens may become harmful in a certain context (Terrain Theory), depending on the overall health and resilience, immune function, stress levels, emotional state, gut function, microbiome etc.
Health (esp. GI) is a key factor in resilience against infection and taking a natural approach is essential for immune support.
5
Q
What are some of the new immune challenges in our modern times?
A
- Dysfunctional immune programming due to less diverse early pathogen exposure, compromised gut / microbiome.
- New antigens - increased consumption of allergenic foods, exposure to toxins (e.g., mould).
- Reduced resilience due to unhealthy lifestyles e.g., metabolic dysfunction, oxidative stress.
- Overuse of antibiotics leading to antibiotic-resistant infections.
Resulting in potentially suboptimal immune response to infection, yet with higher levels of inflammation, autoimmunity and allergy.
6
Q
What is the innate immune system? Provide THREE examples of the first and second lines of defence.
A
Inborn / non-specific defence mechanism.
First line - External:
1. Physical barriers:
Skin, mucous membranes
2. Chemical barriers:
Sebum
Sweat
Stomach acid
Tears
Mucus and SIgA
Cerumen
Tissue fluids
Vaginal bacteria
Second line - Internal:
1. Phagocytes:
Monocytes
Macrophages
Neutrophils
Eosinophils
2. Inflammatory response basophils / mast cells
3. Fever
4. Interferons
5. Complement system
6. Natural killer cells
7
Q
What is the adaptive / acquired immune system? Provide TWO examples.
A
Specific defence mechanism. Third line of defence.
- Cell mediated T cells
- Antibody mediated B cells
8
Q
What is effective immunity dependent on?
A
- Healthy barrier tissue integrity, where pathogens make first contact - skin, gut, lungs etc.
- Presence of secretions - tears, saliva etc., which have antimicrobial properties. Healthy mucus production is an essential barrier.
- Probiotic bacteria occupy space on epithelial surfaces, secreting lactic acid and natural antibiotics.
- Immune activity is concentrated at key points of entry - MALT / GALT (e.g., tonsils, Peyer’s patches), containing large numbers of immune cells including B cells, secreting sIgA.
- Healthy innate immune response involves mobilisation of leukocytes such as macrophages, dendritic cells, neutrophils, mast cells etc.
They survey and recognise pathogens via pattern recognition (PAMPs, DAMPs) and neutralise them via phagocytosis, production of reactive oxygen species, lactoferrin etc. Many innate immune cells then act as antigen-presenting cells (APCs) to the adaptive immune system, which can support with a more tailored response to a specific threat. - Inflammation - ‘quarantines’ a specific area and ↑ immune activity.
9
Q
After antigen presentation, naïve T-helper cells can differentiate into either ____ , ____ , ____ or ____
A
Th1, Th2, Th17 or T-reg cells.
10
Q
What can the over-activation of either Th1 or Th2 pathway lead to?
A
Over-activation of either pattern can cause disease.
Either pathway (Th1 / Th2) can downregulate the other, leading to a ‘see-saw’ type effect, referred to as Th1 / Th2 dominance.
11
Q
Name Th1 cells:
- function
- cytokines promoting production
- triggers
A
Function: Defence against intracellular pathogens (e.g., viruses). Anti-cancer / tumour.
Cytokines promoting production: IL-12 promotes differentiation into Th1.
Triggers: Production of cytotoxic (CD8) T-cells, macrophages, IFN-γ and TNF-⍺/β.
12
Q
Name Th2 cells:
- function
- cytokine/s promoting production
- triggers
A
Function: Defence against extracellular threats (e.g., parasites).
Cytokine/s promoting production: IL-2, 4 and 5 promote Th2.
Triggers: Production of IL-4, -5, -10 and -13, ↑ B-cell antibody production (e.g., IgE). Induces eosinophils.
13
Q
Name Th17 cells:
- function
- cytokine/s promoting production
- triggers
A
Function: Defence against extracellular pathogens.
Cytokine/s promoting production: IL-1, IL-6 and TGF-β promote Th17 cells.
Triggers: Produce the pro-inflammatory IL-17, IL-6, IL-22 and TNF-α and are often involved in the chronic stage of inflammatory diseases incl. allergies and some autoimmune disease.
14
Q
Name T-reg cells:
- function
- cytokine/s promoting production
- where they are produced
A
Function: Modulate and deactivate the immune response.
Cytokine/s promoting production: T-reg cells produce ‘transforming growth factor-beta’ (TGF-β) and IL-10. Both cytokines are inhibitory to helper T-cells.
The majority of peripherally produced T-reg cells originate in the GALT.
15
Q
What can Th1 dominance lead to?
A
chronic inflammation and autoimmunity.
16
Q
What can Th2 dominance lead to?
A
allergies (incl. asthma / the atopic triad).
17
Q
The optimal scenario is a well balanced _____ and _____ response, balanced via ______ and various ______ to down- or upregulate the balance.
A
Th1
Th2
the T-regulatory cells
nutrients
18
Q
Different Th Helper cell profiles present at different stages of the disease. What pathway will dominate in acute and ongoing eczema?
A
In acute eczema, Th2 cells predominate, but ongoing inflammation / damage results in increased Th1/Th17.
19
Q
What clinical indications we may see in the case history of someone with low immunity?
A
- History of increased susceptibility to, severity of, or prolonged infections, e.g., respiratory, urogenital, skin etc.
- Fatigue, loss of appetite, weight loss, fevers, chills, aches and pains, enlarged lymph nodes. Specific symptoms, depending on site of infection - soreness / pain, coughing, runny nose, phlegm.
20
Q
What tests can be indicative of low immunity?
A
- Blood: Low WBC count
- Stool or saliva: Low sIgA
- Positive test for pathogen or antibodies - e.g., blood antigen test for hepatitis and EBV antibodies, urine testing for STDs, stool testing for gut pathogens, other microbiome testing (e.g., vaginal).
21
Q
What impact does breastfeeding have on immunity?
A
Breastfeeding (GOS, other prebiotics, colostrum, growth factors, maternal immune cells) enhance the maturation of immunity and the microflora.
22
Q
Discuss ‘Hygiene hypothesis’, why is it important for neonates?
A
- ‘Hygiene hypothesis’ - pathogen exposure is needed for the neonatal immune system to develop.
- Inadequate antigen exposure is associated with increased atopic diseases and autoimmunity.
- Neonates are born with a TH2 immune bias, and exposure to pathogens increases TH1, achieving immune learning and balance, in parallel with acquisition of gut microflora. Lack of exposure is linked to increased atopic allergy.
23
Q
Name FIVE causes and risks of low immunity
A
- Poor nutrition (e.g., high refined sugars, alcohol) / nutrient deficiencies, especially zinc and vitamin A, D and C.
- Immunosuppressants e.g., corticosteroids, methotrexate, azathioprine.
- Gut / microbiome - commensals offer direct immune protection and programme a healthy immune response. Compromised with c-section, formula-fed, antibiotics, overly hygienic upbringing, dysbiosis / low sIgA, PPIs, NSAIDs, steroids.
- Impaired barrier defences - poor skin quality (e.g., topical steroids / irritants, nutrient deficiencies such as zinc and EFAs), damaged lungs (e.g., smoking, pollutants), gut permeability, tonsillectomy, adenoidectomy, appendectomy.
- Emotional (incl. fear), chemical (e.g., smoking) and physical stress (e.g., overtraining) – ↑ cortisol inhibits phagocytes, NK cells and lymphocyte activity.
- Poor sleep - ↓ immune memory, ↓ anti-viral cytokines (IL-12 / IFNγ), ↑ inflammatory cytokines (e.g., IL-6), ↓ lymphocyte blastogenesis.
- Heavy metal toxicity can inhibit lymphocyte proliferation.
- Blood glucose dysregulation (consider diet / stress etc.) - hyperglycaemia activates protein kinase C (PKC - enzyme that is involved in controlling the function of other proteins) which inhibits phagocytosis and superoxide production, significantly altering the innate immune response.
- Poor energy delivery mechanisms (e.g., CFS ).
- Disrupted methylation (e.g., due to nutrient deficiencies, SNPs) impairs leukocyte differentiation and maturation. The folate cycle is important for DNA synthesis and repair (requiring folate, B2 and B3).
24
Q
Genetic polymorphisms / SNPs of what vitamin can lead to low immunity?
A
- VDBP = less effective binding / transport of vitamin D. Likely to require more support - sun / food / supplements to attain adequate / good levels.
-
VDR = lower sensitivity to vitamin D.
Likely to require higher levels in order to receive / respond to vitamin D.
VDR induces ‘cathelicidin antibacterial peptide’; represses inflammatory cytokines IFN-γ, TNF, IL6
25
What would you recommend to support the immune function?
* CNM Naturopathic Diet. Optimise the terrain.
* Reduce / eliminate sugar, alcohol, caffeine. Keep a healthy weight.
* Regular activity (avoid under and over-exercising), especially outdoors. Fresh woodland or sea air (phytoncides, mineral content) are especially beneficial.
* Support sleep, reduce stress, toxic exposure. Listen to the body when fighting infection and get bed rest to conserve energy.
* Digestion / GI health is vital - promoting a healthy microbiome with a high prebiotic diet; chewing well; time to digest when relaxed.
26
How does Vitamin A support immunity and what may be the consequences of its deficiency? Name the form and dosage.
Retinol acetate / palmitate
Dose: 2500–5000 iu / day.
Supports lymphatic tissues and immune cells, maintains lung barrier function. Deficiency associated with severe respiratory tract infections, including pneumonia.
27
How does Vitamin C support immunity and what its deficiency is associated with? Name the form and dosage.
Buffered form e.g., magnesium ascorbate,
ester-C 1–5000 mg / day.
Supports the innate and adaptive immune systems and epithelial barrier. Deficiency = higher susceptibility to infections. Prevention requires adequate, if not saturating plasma levels.
28
How does zinc support immunity? Name the form and dosage.
Chelated form e.g., zinc citrate, gluconate 10–15 mg / day.
Inhibits viral replication, permeability of barriers, and ↑ specific anti-viral immune defences.
It boosts immunity in children and can reduce respiratory infection risk in the elderly.
29
How do probiotics support immunity? Name the dosage.
1–30 billion, depending on strain.
Act as a ’low level’ challenge to the immune system, via action on toll-like receptors in GALT. Various probiotics boost sIgA, incl. several Lactobacilli spp. and Saccharomyces boulardii.
30
How does vitamin D support immunity? Name the form and dosage.
Cholecalciferol (D3)
Test: 1000-2000 iu /day or higher if deficient 10-20000 iu.
*Enhances protective innate immune responses and helps maintain self-tolerance by dampening excessive immune responses.*
Increases regulatory T-cells and downregulates T-cell-driven IgG production. Shifts towards Th2.
Lower levels are associated with higher susceptibility, complications, and mortality. Optimal serum levels are associated with reduced risk of acute URTs.
31
How do Beta glucans support immunity? Name the dosage.
900 mg
1,3 and 1,6 support innate and adaptive immunity and are particularly supportive against upper respiratory tract infections.
They exert immune-modulating and anti-tumour effects.
32
How do medicinal mushrooms support immunity? Name TWO and their mode of action.
Medicinal mushrooms contain polysaccharides including beta-glucans which interact with receptors in GALT - Dectin-1, TLR2 and 6, boosting sIgA and TH1 immunity. In addition, they have a prebiotic effect.
* **Reishi** - increases immune cells incl. T-cells, macrophages and NK cells. Cytotoxic to cancer cells.
* **Chaga** - immunomodulator, anti-viral.
* **Shiitake** - increases phagocytes, T-cells, NK cells and interferons.
* **Maitake** - increases in Th1. Stimulates macrophages and NK cells. Anti-cancer.
33
Name FIVE nutrients that can be used DURING infection with rational - include form and dosage.
**Vitamin A** - Retinol acetate / palmitate
5000 iu.
Anti-viral activity, including against measles and norovirus. Reduces infection associated with otitis media.
**Vitamin C** - Buffered form (magnesium ascorbate, ester-C).
1000 mg per hour for up to 6 hours.
Possible to take 1 g / hr until bowel tolerance reached.
It inhibits virus multiplication and improves immune cell function.
**Zinc** - Chelated form (zinc citrate).
15–30 mg / day.
Shows antiviral properties against many viruses, including Hep C, and HIV. Low levels inhibit the replication of influenza and other viruses.
**Vitamin D** - 5000 iu.
Upregulates the production of antimicrobial peptides.
**Elderberry** - 3–8 g
Contains phytochemicals (including cyanidin-3-glucoside and cyanidin-3-sambubioside) which ‘blunt’ hemagglutinin spikes, preventing viral cell entry. It strengthens the immune response against influenza, speeding recovery and decreases URT symptoms in general according to a recent meta-analysis.
**Beta-glucans** - 900 mg
Reduce URTIs in elderly and children.
**Echinacea** - 4000 mg
Immune enhancing / modulating (alkylamides); activates phagocytes and NK cells. Can decrease the duration / severity of acute RTIs.
**Lysine** - 1–3 g
Inhibits viral replication. Especially for herpes simplex infection, so can help cold sores. Also avoid arginine and consider low arginine diet.
34
What is Cytokine Storm Syndrome and what can it lead to?
An excess of pro-inflammatory cytokines which can cause lung tissue damage, respiratory distress, pneumonia, or even death.
35
Is it safe to recommend elderberry to people who are susceptible to immune hyperresponsiveness and why?
Elderberry is actively **antiviral**, and so should reduce viral load, reducing overall inflammation. It is also a powerful **antioxidant**, reducing damage, so its overall effect is very likely beneficial.
Ensuring use of a combined nutrient protocol (rather than high dose single nutrient) will also help to ensure the effect on the immune system is synergistic. For example, vitamin D is supportive as deficiency may predispose to cytokine storm.
36
Name 1) the causal agent in producing the Coronavirus disease of 2019 (COVID-19) and 2) the receptor-binding domain of the COVID virus.
1) SARS-CoV-2
2) angiotensin converting enzyme-2 (ACE-2) - enables viral entry.
37
Name FIVE COVID-19 risk factors (for more severe disease). Include at least one nutritional deficiency.
**Metabolic dysfunction** can lead to chronic inflammation - TNFα, IL-6 and IL-1β are upregulated in the adipose tissue.
Obesity, diabetes mellitus, CVD and non-alcoholic fatty liver disease negatively influence the progression and prognosis of COVID-19.
**Nutritional deficiencies:**
Vitamin D (immunomodulatory, ↓ inflamm. cytokines); vitamins C, B6, selenium, zinc, DHA and EPA.
**Dysbiosis** = infection, and infection = dysbiosis.
Depletion of immunomodulatory gut bacteria such as Bifidobacterium spp., Faecalbacterium prausnitizii and Eubacterium rectale.
**Metabolic endotoxaemia** - the spike protein and LPS interaction leads to aggravated inflammation.
38
Outline the basics of naturopathic approach to COVID-19
* CNM Naturopathic Diet with a focus on plant protein, less poultry / red meat, less sugar and alcohol.
* Adequate rest, avoid suppressing symptoms.
* Support holistically - especially stress, sleep, blood glucose, toxic load, oxidative stress. Healthy weight management.
* Support innate immunity - most neutralise COVID virus by mucosal IgA, with no / few symptoms. E.g., with probiotics, beta-glucans, vitamin C, etc.
* Ensure optimal ranges of vitamin D.
* Microbiome support - restore diversity, gut barrier support, reduce inflammation (e.g., with prebiotics such as GOS which can raise Bifidobacterium; probiotics and polyphenols).
39
Considerations for severe or ‘long COVID’
Focus on wider system support, esp. supporting inflammation, and any other specifically affected areas - mitochondrial function, gut, lung dysfunction etc.
40
Name THREE nutrients for COVID-19 support, including dosage.
**Quercetin** (500–1000 mg, twice daily) - impairs spike protein binding to ACE2; inhibits viral replication; possibly anti-coagulation.
**Resveratrol** (200 mg / day or eat resveratrol-rich foods) - inhibits SARS CoV-2 in vitro; a potent antioxidant.
**Turmeric** (Curcuma longa) 1.5 g daily - appears to have cytoprotective effects of type II alveolar cells; decreases the population of inflammatory macrophages; ACE2 blocking. Reducing pulmonary and cardiovascular complications.
**Berberine** 400 mg twice daily - interferes with viral replication. Insulin sensitivity; microbiome-balancing.
41
Provide FOUR recommendations for lung support during COVID-19
Lungs can be susceptible to damage / oxidative stress. Lung tissue contains protective antioxidants, including SOD and GPO.
Cease smoking - associated with more severe COVID symptoms.
N-acetyl cysteine (NAC) 1.5 g daily - protects lung tissue; mucolytic, glutathione synthesis (antioxidant effects).
Vitamin D - inhibits microbial entry into lungs (↓ lung permeability).
Anti-microbial herbs - oregano, garlic, thyme, sage.
Diluted grapefruit seed oil, colloidal silver, saline gargled or via nasal douche to clear nose (including biofilms).
Lugol’s solution (iodine) inhaled in a salt pipe.
42
Discuss inflammation, including:
- its definition
- function
- physiological response
- 5 cardinal signs
Inflammation is a normal immune response to tissue damage to localise, eliminate and heal the affected area. It acts as a signal to protect the affected area, rest and allow repair. As an acute response (i.e., acute inflammation), it provides an important immune function.
*Involves:*
Vasodilation, increased tissue permeability, blood clotting, accumulation of fluid, recruitment of immune cells.
*Cardinal signs:*
Redness, heat, oedema, pain, loss of function.
43
What happens if inflammation is not targeted, time-limited and proportionate?
If not targeted → directed at self tissue (autoimmunity) or non-harmful antigens (allergy).
if not time-limited → not fully resolved (latent infection, scar tissue), it can lead to local or systemic dysfunction.
If not proportionate → chronic inflammation may play a key part in many clients’ clinical issues but is particularly linked to chronic diseases such as neurodegenerative disease, cardiovascular disease and cancer.
44
Name THREE potential presentations of chronic Inflammation in clinic.
* Symptoms / signs, e.g., pain, swelling, aches, joint stiffness, redness and heat.
* Diagnosis / symptoms of an inflammatory condition, e.g., IBD, CVD.
* Related conditions with inflammatory element, e.g., depression.
* History of latent / unresolved infection (e.g., periodontal disease), high stress, sports ‘overtraining’, use of steroids and analgesics.
45
What tests (GP and functional) can be indicative of chronic inflammation?
* GP tests - High CRP, WBC, ESR, fibrinogen, low vitamin D.
Imaging e.g., ultrasound, MRI may show local tissue inflammation.
* Functional tests - hsCRP, high omega 6:3 ratio, low omega-3.
Genetics - FADS1/2, IL-6, IL-13, TNF-⍺, HLA, VDR.
46
Name THREE mediators and their mode of action in the pathogenesis of chronic inflammation
* Cytokines - TNF⍺, IL-6, IL-1 (e.g., IL-1β) upregulate inflammation.
* Histamine - promotes vasodilation and vascular permeability.
* Kinins - (e.g., bradykinin) ↑ vasodilation / permeability and ‘pain’.
* Nuclear Factor-Kappa B (NF-kB) - activates gene transcription, upregulating a range of inflammatory processes.
47
What activates NF-kB?
It is activated by:
– Cytokines (e.g., TNF-⍺); reactive oxygen and nitrogen species.
– LPS (consider disturbed gut mucosal barrier).
– Homocysteine.
– Heavy metals (e.g., arsenic); polycyclic aromatic hydrocarbon
48
What pathologies NFкB dysregulation has been linked to?
Cancer and autoimmune / inflammatory disorders such rheumatoid arthritis and IBD.
49
What are eicosanoids and their role in chronic inflammation? Provide examples.
Eicosanoids = locally-acting hormone-like messengers made by the oxidation of omega-3 and 6 fats in cell membranes.
They can exert different degrees of pro-inflammatory activity depending on the fatty acid precursor used.
Include **prostaglandins, thromboxanes, leukotrienes, prostacyclins,** and **lipoxins**.
- Prostaglandin E2 (PGE-2) ↑ vasodilation, platelet aggregation, histamine and kinins.
- Certain cytokines (e.g., TNF, IL-1) activate COX and convert arachidonic acid to PGE-2.
- Leukotriene B4 (LTB-4) is inflammatory (converted by 5-LOX).
50
What response is co-ordinated to prevent secondary tissue damage in chronic inflammation?
The production of receptor antagonists to pro-inflammatory mediators.
* T-reg cells produce **TGF-β** and **IL-10** - both are inhibitory to helper T-cells (i.e. inhibiting Th1 and 2 activity).
* Production of ‘less inflammatory’ **PGE-1**, **PGE-3**, **resolvins** and **protectins** from omega-3 fatty acids in cell membranes.
* Increase in **lipoxins** - downregulate NFkB and many aspects of immune response. Formed from AA or LTB-4 by LOX enzymes.
51
Causes of chronic inflammation
**Predisposition** - we have a high inflammatory load to start with.
**Inadequate inflammatory response** - we don’t have the resource to resolve it properly, so it persists.
**Inadequate resolution** - we raise inflammation, but can’t switch it off.
**Ongoing damage** - continual exposure to source of damage e.g., RSI, oxidised Tgs.
**Inadequate recovery / repair** - we don’t have time / resources to get better.
52
How does the Western diet and lifestyle drive chronic inflammation?
High refined sugar (increases free radicals and AGE), high omega-6 / low omega-3 (increases PGE-2), trans fats.
Pathogen-associated molecular patterns (PAMPS) of dead bacteria in poor-quality processed, pre-chopped foods.
53
Provide an example of how polymorphisms/SNPs can impact chronic inflammation.
* FADS1, FADS2 polymorphisms (genes that code for delta-5 and delta-6 desaturase) - lead to increased inflammation.
* SNPs on pro-inflammatory genes (e.g., TNF, IL-6) are associated with an upregulated inflammatory response.
54
Discuss THREE lifestyle/environmental factors that may be a risk factor for chronic inflammation.
* **Chronic stress** - results in glucocorticoid receptor resistance = failure to downregulate inflammatory responses. Low cortisol / cortisol resistance can ↑ inflammation.
* **Poor sleep quality / short sleep duration** - studies show this ↑ levels of CRP, IL-6, fibrinogen and TNF-⍺, especially in women.
* **Excess exercise** with inadequate recovery (‘overtraining’) can increase inflammation via oxidative stress, impact on sleep, etc.
* **Oxidative stress** - results in inflammation and vice versa e.g., from air pollution, smoking, alcohol, etc. Low anti-oxidant status.
* **High toxic load** - can drive chronic low-grade inflammation.
* **Obesity / overweight**
55
What is the link between metabolic endotoxaemia and chronic inflammation?
Metabolic endotoxaemia raises LPS in the blood and interacts with toll-like receptors = chronic low-grade inflammation.
56
How can sex hormone imbalance impact chronic inflammation?
Oestrogen is anti-inflammatory, but in excess can be pro-inflammatory. Low testosterone promotes inflammation in men.
Maintaining healthy sex hormone levels reduces the risk of several inflammatory diseases.
57
How inadequate immune response can lead to chronic inflammation?
* Persistent or latent infection (e.g., viral, parasitic, etc.)
* Excess myeloid-derived suppressor cells - normally downregulate inflammation to prevent tissue damage.
58
Discuss ONE allopathic medical management of chronic inflammation including its side effects.
* **NSAIDs**: E.g., ibuprofen, naproxen.
Inhibit COX-1 / COX-2 and ↓ prostaglandin synthesis.
Side effects: GIT bleeding (esp. > 65 years), peptic ulceration, renal damage, CVD, agranulocytosis (severely low levels of neutrophils).
* **Corticosteroids**: E.g., prednisolone.
Inhibit inflammatory proteins blocking NF-kB, induce expression of anti-inflammatory proteins and inhibit 5-LOX and COX-2.
Side effects: Weight gain, diabetes, hypertension, visual disturbances (blurring), osteoporosis. HPA and immune suppression (increased risk of serious infections).
* **DMARDS** (disease-modifying antirheumatic drug): E.g., methotrexate, azathioprine.
Side effects: Bone marrow depression, agranulocytosis, increased risk of infection, throat ulcers.
59
What would your naturopathic approach focus on when addressing chronic inflammation?
Look at wider system factors as per causes and risk factors. Focus on:
* Blood glucose - dietary support to stabilise glucose and insulin.
* Gut health - high fibre, low allergen / PAMP diet, protocols for dysbiosis / permeability as appropriate.
* Oxidative stress - high antioxidant diet or supplement support.
* Stress, sleep and recovery support.
* Immune function - support the immune system to deal with latent infections, periodontal disease, etc.
* Methylation - background support for wide range of functions.
60
Turmeric for chronic inflammation, include dosage and mode of action.
Dose: 500–2000 mg. Whole root.
Anti-inflammatory - blocks NF-κB activation and inhibits pro-inflammatory cytokines like IL-1β and -6.
May be better than curcumin for antimicrobial support and cancer.
61
Curcumin for chronic inflammation, include dosage and mode of action.
Dose: Up to 1000 mg; less if absorption ↑ via emulsification, liposomal or piperine (200-400 mg).
Key antioxidant in turmeric, with antioxidant and anti-inflammatory properties. It regulates cytokines such as IL-1β, IL-6, IL-12, TNF-α, and IFN-γ and reduces PGE-2 and 5-LOX.
Reduces joint inflammation / osteoarthritic pain.
62
Ginger for chronic inflammation, include dosage and mode of action.
Dose: 500–1000 mg.
Ginger inhibits TNF-α and PGE-2 through inhibition of COX-2 and reduces inflammatory joint pain.
63
Plant sterols for chronic inflammation, include dosage and mode of action.
Dose: 3 g.
In some studies reduces inflammation - lowering IL-6, CRP, TNF-α.
64
Boswellia for chronic inflammation, include dosage and mode of action.
Dose: 250‒500 mg.
Inhibits inflammation by reducing 5-LOX activity.
Reduces pain and shown to improve knee-joint function.
65
OPC (oligomeric proanthocyanidins) from pine bark / grapeseed for chronic inflammation, include dosage and mode of action.
Dose: 100–500 mg.
reduce inflammation by inhibiting COX-2, ↓ ROS and ↓ matrix metalloproteinase (MMP) activity, supporting tissue structure.
66
EFA esp. EPA for chronic inflammation, include dosage and mode of action.
Dose: 1 g of actual EPA or higher as required.
High-potency omega-3 from fish oil can reduce inflammation by inhibition of the PGE2 pathway.
Inhibiting NFκB, TNF-α and Interleukin-6.
67
Vitamin D for chronic inflammation, include dosage and mode of action.
Dose: 2000‒10000 iu.
- Inhibits eosinophils, ↑ tolerogenic factors in dendritic cells.
- Improves T-reg function, decreases proliferation of all T-helper cells but with an accompanying shift away from Th1 and towards Th2.
- Reduces inflammatory cytokines (e.g., IL-6 and TNF-α).
68
What nutrients are needed to optimise the conversion of ALA into EPA (co-factors for delta-6 and -5 desaturase) in application to chronic inflammation?
zinc, magnesium, B3, B6, and vitamin C
69
Provide rationale for using quercetin, reishi and probiotics for chronic inflammation. Include dosage.
* **Quercetin** 250-1500 mg / day
inhibits LOX and COX; a potent down-regulator of NF-κB.
* **Reishi** (Ganoderma lucidum) 3-9 g / day.
Triterpenes are anti-inflammatory - reduce the activity of NF-kB.
* **Probiotics**
reduce inflammatory markers such as TNF-α and IL-6.
70
What is an autoimmune disease and when does it become pathological?
Involves the immune system mistakenly attacking the body’s own cells, resulting in ill-health and disease.
AI is present in healthy individuals to eliminate degraded self-antigens but becomes pathological if there is a breakdown in self-tolerance.
The tissue / system targeted will dictate the manifestation, resulting in different disorders.
71
What mechanisms regulate self-tolerance in the body? What can lead to a potential loss of self-tolerance?
‘Central tolerance’ ensures:
- self-reactive lymphocytes are deleted in the thymus.
- mature self-reactive T-cells are deleted in peripheral tissues.
Potential loss of self-tolerance can happen due to dysregulation of autoreactive T-cells:
- T-cells may not be fully exposed to self-antigens or are released early into circulation, and so are not fully ‘trained’.
- Peripheral regulation’ may be inadequate - there may be too few T-reg cells to manage any autoreactive Th cells.
72
What role do Th1, Th2 & Th17 play in the pathophysiology of autoimmune disease?
* Both Th1 and Th17 cells are important drivers of the inflammatory process in tissue or organ-specific autoimmunity.
* E.g., Th1 increases macrophages via cytokine IFN-γ in Crohn’s disease. Th17 also increases inflammatory cells, especially neutrophils.
* However, systemic AI conditions, like SLE and Sjögren's are characterised by Th2 dominant cytokine production.
* In pregnancy, Th2 immunity predominates, sometimes resulting in relief of Th1 type AI, but symptoms can rebound post-partum.
73
How can cross-reactivity trigger an autoimmune disease?
The presence of an autoantigen (or mimic) may trigger a reaction against specific self-tissues. This could be:
– Mimicry - an antigen looks like a self-antigen e.g., foods or pathogens.
– Tissue damage / injury from previous bacterial or viral infection which releases self-antigens.
74
What role does the Major Histocompatibility Complex play in autoimmune disease?
The Major Histocompatibility Complex (MHC) encodes cell surface proteins (human leukocyte antigens / HLAs) and plays a key role in antigen presentation and prevention of the immune system targeting its own cells. Dysfunction of this is associated with AI disease.
75
Name TWO autoimmune pathologies and microbe species that are associated with it.
**Rheumatoid arthritis**
- Prevotellacopri
- Fusobacterium nucleatum
- Porphyromonasgingivalis (periodontitis)
- Klebsiella pneumoniae
- Proteas mirablis (gut and UTIs)
- Epstein-Barr virus
**Inflammatory bowel diseases**
- Fusobacterium nucleatum
- Sulfidogenic bacteria e.g., Desulfovibrio spp
- Bilophiliawadsworthia E.coli
- Clostridium difficile
**Multiple sclerosis**
- Clostridium perfringens
- Epstein-Barr virus
**Graves’ and Hashimoto's**
- Yersinia enterocolitica.
**Systemic lupus erythematosus**
- Epstein-Barr virus.
**Ankylosing spondylitis**
- Klebsiella pneumoniae.
**Psoriasis**
- Streptococcus pyogenes
76
What foods may be involved in the cross-reactivity in autoimmune disorders?
Peptide sequences in foods may be similar to human tissues. This ‘molecular mimicry’ can induce or exacerbate AI. Food proteins may be modified by toxins, making them more reactive.
* Peptide sequences in **dairy** and **wheat** are similar to certain molecules, such as myelin oligodendrocyte glycoprotein and human islet cell tissue, so may be a factor in MS and other conditions.
Gliadin is a molecular mimic of transglutaminase, which is abundant in the thyroid gland.
A gluten-free diet improves thyroid antibodies in Hashimoto's. In several studies, gluten-free diet improves disease in MS.
77
Discuss some of the proposed mechanisms in autoimmunity (epitope spreading, bystander activation and cryptic epitopes).
* **Epitope spreading** - antibody or cellular response to a given antigen may extend from one ‘epitope’ on the antigen to other epitopes of the antigen, or adjacent antigens, increasing damage.
* **Bystander activation** - infections activate antigen-presenting cells such as dendritic cells, which then activate autoreactive T-cells.
* **Cryptic epitopes** - some self-epitopes are 'hidden’ from immune recognition, reducing autoantigenicity. If produced in large quantities or freed (e.g., damage), autoimmune T-cell reactions may occur.
| Epitope = part of an antigen, to which a single antibody can bind
78
How genetics can play a role in developing an autoimmune disease? Name THREE SNPs associated with autoimmunity.
* HLA (MHC) SNPs - disruption of antigen recognition and self-tolerance.
HLA-DRB1 in RA and MS
HLA-DQA1 / HLA‐DQ8 in coeliac disease.
* SNPs predisposing to inflammation increase AI risk.
TNF-⍺ IL-2, IL-12, IFNɣ in Graves’ disease.
* Methylation SNPs and alterations in DNA methylation have been linked to many AI conditions, including RA and MS.
* VDR, CYP24A1 and CYP27B1 (vitamin D conversion) SNPs are associated with increased incidence of AI.
79
Name THREE causes / risk factors of an autoimmune disease - not dysbiosis.
* **Emotional trauma** (resulting in immune dysregulation) or **infection** is a preceding factor in 80% of autoimmune sufferers.
* **Gluten** is a key food source of molecular mimicry and inducer of intestinal permeability.
* **Environmental toxins** induce oxidative stress, contributing to loss of immune tolerance e.g., heavy metals, pesticides, mycotoxins.
* **Vitamin D def**. - vit. D ↑ T-reg cells and maintains self-tolerance. Deficiency ↑ risk of MS and pancreatic β cell destruction (T1DM). Many AI diseases show a geographical latitude-dependent prevalence, potentially related to vitamin D levels and **VDR SNPs**.
80
Discuss how autoimmunity is linked to dysbiosis and intestinal permeability.
* Dysbiosis and a thinning of the mucosal barrier causes too much cross-talk between GI microbes and the wider immune system. This is how coding for antibodies to seemingly commensal bacteria can happen.
* Intestinal permeability - because the intestinal epithelial barrier controls the equilibrium between tolerance and immunity to non-self antigens.
81
78% of autoimmune patients are female. Why does being a female may increase autoimmunity risk?
* Variations in disease activity are often observed throughout the menstrual cycle, pregnancy and breast-feeding.
* The immune system of females tends to skew towards Th2 dominance and high oestrogen also has immune stimulatory, pro-inflammatory properties.
* High exposure to oestrogen through contraception, HRT and xenoestrogens.
82
How can an autoimmune condition be presented in a clinical setting?
* Diagnosis of an AI condition or expressing symptoms, suggesting an AI disease e.g., bilateral joint pains, hand deformities - RA.
* History of pathogen exposure, gut issues (dysbiosis, food reactions, esp. gluten), high toxic exposure, family history, stress.
* GP tests - inflammatory markers (raised CRP, ESR). Fluorescent antinuclear antibody test (FANA) - diagnostic of specific autoantibodies, e.g., RA: Rheumatoid factor. Low vitamin D.
* Functional tests - Cyrex Array 5 Multiple AI Reactivity Screen. Comprehensive gut profiling e.g., GI effects, GI EcologiX.
* SNPs - predisposing to inflammation (TNFα), VDR, HLA.
83
Naturopathic approach to autoimmunity. What would be your recommendations?
* Particular focus on gut / food sensitivity: digestion, microbiome balance and intestinal / mucosal barrier.
* Diet - blood glucose balancing / low GL, omega 3-rich (optimising the omega-3 to -6 ratio).
* Eliminate gluten and remove / reduce other allergenic foods (check with test, food diary or exclusion).
* Specific therapeutic diets such as paleo or autoimmune protocols (AIP / Wahl’s), depending on the individual.
* Test and support optimal vitamin D levels.
* Support methylation.
* Support pathways of detoxification and elimination.
* Stress support and optimise sleep.
* Natural anti-virals if potential viral trigger (assume it is still there), e.g., L-lysine, olive leaf, St John’s wort (Hypericum perforatum). As well as zinc and vitamin C. Combine with a low arginine diet.
84
What is the focus of the ‘autoimmune protocol’?
Emphasises nutrient-dense foods and eliminates foods that may stimulate the immune system, cause hormone dysregulation, or harm the GI environment.
Focuses on dietary / lifestyle factors known to modulate immune function, gut health, and hormone health including adequate sleep, managing stress, being active (not
over-training).
After a period of time, some of the excluded foods can be reintroduced usually if the disease is in remission (or not progressing); the GIT is working effectively or a person can manage without DMARDs, steroids or NSAIDs.
85
Name FIVE foods to include / exclude in the autoimmune protocol.
Include:
- Vegetables (8 portions a day) esp. green leafy veg, a rainbow of colours, cruciferous, onions and garlic, sea vegetables.
- Grass-fed organic meat.
- Fish and shellfish.
- Herbs and spices.
- Healthy fats (e.g., oily fish, EVOO, avocado).
- Probiotic / fermented foods e.g., sauerkraut.
- Glycine-rich foods (e.g., bone broth).
Exclude:
- Alcohol, dairy, grains, legumes, refined sugar / oils.
- Eggs (esp. the whites).
- Nuts (incl. butters, flours, oils).
- Seeds (incl. seed oils).
- Nightshades.
- Sweeteners (even stevia).
- Emulsifiers, thickeners and food additives.
- Potentially gluten-cross reactive foods.
86
What foods to include / exclude in Wahl’s autoimmune protocol?
Include:
- Green leafy vegetables and sulphur-rich vegetables e.g., cauliflower.
- Brightly-coloured fruit, like berries (phytonutrient content).
- Grass-fed meat and oily fish.
- Fat from plant and animal sources, especially omega-3s.
Exclude:
- Dairy products and eggs.
- Grains (including wheat, rice and oatmeal) - due to lectin content.
- Legumes (beans and lentils) - due to lectin content.
- Nightshade vegetables (e.g., tomatoes, aubergine, potatoes) - due to their solanine content.
- Sugar.
87
Supplements for autoimmunity: Vitamin D - dosage and mode of action
Dose: 2000–10000 iu.
Interacts with VDR which modulates gene transcription, resulting in functional changes in multiple immune cells:
- Inhibits CD4 Th1 cells, and their production of cytokines such as IL-2, interferon (IFN)-γ, and TNFα.
- Increases T-reg activity and suppresses Th17.
88
EFAs for autoimmunity - dosage and mode of action
Dose: 1 g of actual EPA or higher as required.
High-potency omega-3 from fish oil can reduce inflammation by inhibition of the PGE2 pathway.
High dose EPA reduces pain in RA.
89
Curcumin for autoimmunity:
- dosage
- improves clinical outcomes in what pathologies
Dose: up to 1000 mg, 200–400 mg if absorption increased.
Ulcerative colitis, with potential for MS, lupus and RA.
90
Supplements for autoimmunity: Resveratrol - dosage and mode of action.
200 mg / day.
- has been shown to reduce Th17 cellular lines
- downregulates NF-KB and COX-2.
91
Supplements for autoimmunity: Alpha lipoic acid - dosage and mode of action.
200 mg / day.
- **antioxidant**, raises intracellular glutathione levels.
- **anti-inflammatory** - reduces inflammatory markers such as CRP, IL-6 and TNF-α.
92
Supplements for autoimmunity: medicinal mushrooms - mode of action.
Beta-glucans exert immune-modulating effects.
E.g., ‘cordycepin’ in Cordyceps (Cordyceps sinensis) has been shown to inhibit IB-1β-induced MMP expression in rheumatoid arthritis synovial fibroblasts.
93
GI approach in autoimmunity. Name ONE probiotic strain that has been shown to improve a particular disease.
Gut permeability support - vitamin A, C, zinc, glutamine, NAG (N-Acetyl Glucosamine), collagen.
If persistent pathogens, consider dysbiosis protocol - oregano, garlic, berberine etc.
Probiotics improve GI symptoms and inflammation in RA, UC, and MS.
- Lactobacillus / Bifidobacterium combination improves disease and CRP in RA.
- Evidence of dysbiosis (low Lactobacillus, Prevotella) in MS; L. reuteri may improve symptoms.
- L. salivarius and L. rhamnosus GG reduce inflammatory cytokines in IBD.
94
What is Systemic Lupus Erythematosus - prevalence, signs/symptoms, and how is it diagnosed?
A chronic inflammatory disease characterised by autoantibody response to nuclear and cytoplasmic antigens, causing multi-system dysfunction.
*Signs / symptoms:*
Fatigue, joint inflammation, seizures, renal damage, photosensitivity, pulmonary, cardiac, cytopenia and digestive issues. Butterfly skin rash. Malaise, fever.
*Relapsing and remitting pattern.*
90% of sufferers are female.
Diagnosed by presence of anti-nuclear (*ANA*) and double-stranded DNA (*dsDNA*) antibodies.
95
Name FOUR causes/risk factors for SLE
* **Genetics** (HLA DR-3/2 - sibling risk 8 to 29-fold higher).
* **Sex hormone imbalance** - more common in women in reproductive years. Oestrogen dominance pattern?
* **Not breastfed** - formula feeding linked. Reduction in microbiome diversity - lower levels of Bacteroidetes and Proteobacteria.
* **Infectious trigger** (e.g., EBV, periodontal disease).
* **Toxins** - silica dust exposure (construction), smoking, drugs.
* **Stress** - low DHEA levels linked to relapses.
* **Low vitamin D levels** - linked to B-cell hyperactivity.
96
Discuss SLE pathophysiology
* Tissue damage occurs through widespread cellular apoptosis and cell debris. Defective clearance allows for the persistence of antigen and immune complex production that deposit in the microvasculature, skin and kidneys.
* Consequent ↓ glycolysis, β oxidation, glucogenic and ketogenic amino acid metabolism impairing energy production (= fatigue).
* Consequent increased blood lipids, oxidative stress and inflammation. Reduced EFA, phospholipid synthesis, methylation, glutathione.
97
Allergy: definition, conditions included in diagnosis, cause
An immune hypersensitivity reaction caused by exposure to a normally harmless substance, such as pollen, cat dander, food.
Includes diagnoses like asthma, allergic rhinitis, and atopic eczema - these conditions may co-exist or progress from eczema in infancy to asthma and hay fever in later childhood (‘the allergic march’). They are often related to illnesses that have been suppressed by drugs.
Symptoms are due to the high level of dysfunctional immune activity and consequent inflammation and oxidative stress.
98
For allergy to exist, what must first occur and how does the 'hygiene hypothesis' play a part in developing an allergy?
Allergen sensitisation.
* Babies are born with a heightened Th2 response potentially predisposing them to allergic reactions.
* Exposure to the normal microbia environment including via vaginal birthing, and the development of the microbiome, promotes a Th1 response, rebalancing the immune response.
* The ‘hygiene hypothesis’ proposes a lack of exposure to sufficient antigens in the first year of life is thought to be one reason for the increase in atopic dermatitis and AI disease.
99
What is meant by microbiome 'bystander suppression' in allergy?
The microbiome is vital to ‘training’ immune response through ‘bystander suppression’, whereby the presence of probiotic bacteria induce tolerance to allergens via T-reg cells.
100
What is the key mechanism in allergic disease?
**Heightened Th2 response**.
IL-4 promotes differentiation of Th cells into Th2 cells.
The Th2 cells secrete IL-4, IL-5, IL-6, IL-13 cytokines to regulate IgE antibody-producing B cells, mast cells and eosinophils.
IgE antibody’s main function is immunity to parasites such as helminths and protozoa.
IgE is the least common Ig but elicits the most powerful response. Binds to mast cells triggering degranulation and histamine release.
101
What is Mast Cell Activation Syndrome?
Mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis.
102
What is the connection between histamine and allergy? What SNPs can slow its breakdown?
Histamine upregulates inflammation, increases oxidative stress, and induces IL-31 production, triggering pruritus and altering skin barrier function in allergic dermatitis.
High histamine may be exacerbated by poor detoxification or high ‘histamine loading’ (e.g., histamine-rich foods like cheese).
SNPs in histamine detoxification genes can slow its breakdown:
- diamine oxidase (DAO)
- histamine-N-methyltransferase (HNMT)
- monoamine oxidase B (MAO-B)
- alcohol dehydrogenase (ADH)
- N-acetyltransferase 2 (NAT2).
103
Provide TWO examples how genes / SNPs can play a role in the progression of an allergic disease.
Certain SNPs can increase susceptibility to allergies in the presence of environmental triggers and impaired immune tolerance.
* The gene **FLG** encodes profilaggrin may lead to increased permeability of the epithelium, increasing atopic dermatitis risk.
* **VDR** SNPs are linked to asthma.
* **HLA** SNPs: many variants incl. HLA-DQB1 are implicated in allergy.
* **TNF-α** and **IL-13** SNPs ↑ the risk of asthma and more inflammation.
* Glutathione SNPs e.g., **GSTP1** and **GSTM1** can increase oxidative stress in allergies and ↑ susceptibility to damage caused by toxins.
104
What are the causes and risk factors of allergies?
* Birth - **c-section-born** babies have reduced microbial diversity and have higher levels of IgA, IgG and IgM until at least 1 year of age, with twice the risk of developing egg and milk sensitisation, a factor in both eczema and asthma.
* **Formula-fed** infants - have lower bacterial diversity associated with an increased risk of eczema and asthma.
* **Maternal** atopy, vaccinations and early antibiotic use, also disrupt gut flora, increasing risk of allergy.
* Introduction of dietary allergens (e.g., peanut, eggs) to breastfed infants from three months of age may help reduce food allergies.
105
Clinical presentation of allergy
* Diagnosis of an allergy or expressing symptoms of an allergy.
* Family history of atopy; history of CS birth, formula-feeding, overly hygienic environment, hospitalisation, antibiotics, childhood stress.
* Dysbiosis, food allergy / sensitivity, ↑ histamine foods, ↑ stress, ↓ sleep
106
What GP and functional tests may be indicative of an allergy?
* GP Test - peak flow (asthma), patch testing, ELISA (enzyme-linked immunosorbent assay) - allergen-specific antibodies in your blood.
* Functional tests - food sensitivity testing e.g., Cyrex 10, York test, Cambridge Foodprint, chemical sensitivity test e.g., Cyrex 11.
107
What SNPs are associated with allergy?
MTHFR, HNMT, DAO, ADH, ALDH, NAT2, MAO-B, VDR, GSTM1/GSTP1 HLA-DQB1, IL-13, TNF-α, FLG.
108
Naturopathic approach to allergy
* ↓ exposure to environmental triggers (symptom diary / Ig testing).
* Particular focus on food sensitivity / gut - digestion, microbiome balance and gut permeability.
* Diet - blood glucose balancing, low GL, omega 3-rich, reduce allergenic foods especially considering dairy / eggs, (check with Ig test, food diary or exclusion).
Consider reduction of high histamine foods.
* Test and support optimal vitamin D levels.
* Support stress and oxidative stress. Buteyko breathing (asthma).
109
Quercetin for allergy: dosage and mode of action.
Dose: 250‒750 mg
- Inhibits LOX, stabilises mast cells, downregulates NF-KB and IL-4.
- Reduces allergic rhinitis symptoms, skin damage in eczema and relaxes smooth muscles in bronchi in asthma.
110
Nettle (leaf) for allergy: dosage and mode of action.
Dose: 500 mg.
Fresh nettle tea can also be taken 3+ times daily.
Reduces effect of histamine, inhibits COX-1 and 2, associated with allergic rhinitis.
111
EFAs especially EPA for allergy: dosage and mode of action.
Dose: 1 g of actual EPA or higher as required.
High-potency omega-3 from fish oil can reduce inflammation by inhibition of the PGE2 pathway.
Reduces asthma incidence and eczema symptoms.
112
TRUE or FALSE
Probiotics can be useful in helping with symptoms of eczema.
True.
Lactobacillus and Bifidobacterium combination reduced incidence of atopic eczema in infants, and reduces eczema symptoms.
113
Vitamin D for allergy: dosage and mode of action.
Dose: 2000–10000 iu
Low maternal vitamin D status is linked to the development of allergy.
Vitamin D increases T-reg activity and regulates antigen presentation.
114
Magnesium for allergy: dosage and mode of action.
Dose: 200–400 mg
Magnesium citrate improves bronchial reactivity in asthma.
115
Vitamin C for allergy: dosage and mode of action.
Dose: 2 g or higher as required.
Supports histamine detoxification - it acts as a co-factor for the enzyme ‘diamine oxidase’ (DAO), which degrades histamine in the gut.
116
Why reducing 'histamine loading' can benefit allergy symptoms? Name THREE ways to do it.
‘Histamine loading’ can contribute to higher levels in addition to the immune response.
* ‘Histamine intolerance’ - sensitivity to dietary histamine.
* Reduce / avoid - fermented foods / drinks such as aubergine, spinach, processed meats, shellfish, dairy (especially cheese), alcohol, dried fruits, avocados.
* Support detoxification of histamine via methylation (HNMT) with folate and B12. DAO (diamine oxidase), which helps break down histamine in gut, with copper, vitamin C and B6.
Acetylation (vitamin B5), MAO-B (vitamin B2), ADH (zinc and vitamin B3).
Reduce toxins that are also detoxified in the same pathways.
