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Healing ArthritisTaming the Flame by Treating Oxidative Stress Susan Blum, MD, MPH

Founder and Director, Blum Center for Health

The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnostics. Thus, Genova Diagnostics does not accept liability for consequences of any actions taken on the basis of the information provided.

Michael Chapman, NDMedical Education Specialist - Asheville

Susan Blum, MD

Board Certified in Preventive Medicine, Certified in Functional Medicine, is Senior Faculty with the Center for

Mind-Body Medicine, and author of The Immune System Recovery Program

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Healing ArthritisTaming the Flame by Treating Oxidative Stress Susan Blum, MD, MPH

Founder and Director, Blum Center for Health

The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnostics. Thus, Genova Diagnostics does not accept liability for consequences of any actions taken on the basis of the information provided.

• Learn about the role of oxidative stress in triggering inflammatory arthritis

• Understand how to test for oxidative stress and how to interpret results as a way to direct your treatment

• Learn how to find and treat the root causes of oxidative stress which might be food, stress, gut health, toxicity or infections

Objectives for This Presentation

Types of Arthritis

• Chronic Inflammatory Arthritis Conditions

– Autoimmune• RA, psoriatic arthritis, ankylosing spondylitis

• Rheumatic disease: ANA + : lupus, Sjögren's syndrome

– Osteoarthritis • Often dismissed as “wear and tear” / “aging”

– Gout• Related to obesity, metabolic syndrome and diet

McCulloch K, et al. Aging Cell. 2017;16(2):210-218.

A

Healthy Joints

• Synovial Membrane

– Soft tissue between the joint capsule and cavity

– Secretes synovial fluid that lubricates the joint

– Protects joint from damage

• Cartilage

– Called “articular cartilage”

– Lines the surface of the bones to protect them from damage

Healthy Joint: Synovial membrane is making good amounts of fluid and the cartilage is healthy and protective

Root Causes of Arthritis

• Autoimmune

– Immune “attack” inside the joints

– Triggers: gut, oral microbiome, infections, toxins

– Damage caused by increased oxidative stress in the joints

• Osteoarthritis

– Aging or injury PLUS systemic inflammation

– Triggers: visceral adipose tissue, metabolic syndrome, gut microbiome

– Damage caused by increased oxidative stress in the joints

Oxidative Stress

• Normal process: low levels of oxidative stress

– Balance between free radicals (also called Reactive Oxygen Species or ROS) from every day biochemistry and immune activity, and the antioxidants we eat in our diet

• Runaway oxidative stress

– Imbalance between too many free radicals and not enough antioxidant activity

• Synovial membranes thickened (hyperplasia)

– Fluid is thinner, less lubricating

• Eventually leads to cartilage, then bone destruction

• People with RA have higher levels of ROS, both system-wide and in

the joint capsule

• Studies have also found low levels of glutathione, vitamins C, A, E,

and beta carotene

• The higher the pain and disability scores, the lower the antioxidant

levels and the higher the oxidative stress markers

– Looked at ROS, lipid peroxides, protein oxidation (OxLDL) and DNA damage (8-OHDG)

RA and Oxidative Stress

Mateen S, et al. PloS One. 2016;11(4):e0152925.

Quiñonez-Flores CM, et al. Biomed Res Int. 2016;2016:6097417.

OA and Oxidative Stress

• Inflammatory compounds from body go into the joints

– Chondrocytes produce ROS

– Directly damage cartilage collagen and change synovial fluid by making it thinner and less protective

• Studies showed low levels of vitamin C were associated with a higher risk of knee OA

– Increasing your vitamin C intake may keep radiographic knee OA and pain from getting worse

Loeser RF, et al. Nat Rev Rheumatol. 2016;12(7):412-20.

Treating Oxidative Stress

• Find and treat the root cause(s)

– Impaired gut health: the gut microbiome

• Key focus in autoimmune arthritis

– Diet: especially low levels of antioxidants

– Stress and trauma

– Environmental exposures

• Heavy metals, pesticides/herbicides, smoking

– Infections

– Obesity: key focus in osteoarthritis

The whole body is effected, not just the joints!

The Gut-Arthritis Connection

• People with RA, PsA, AS: damaged tight junctions, high zonulin and leaky gut

• Gut lumen antigens (including bacterial cell wall proteins) get into the body and trigger an immune and inflammatory response

Fasano A. Physiol. Rev. 2011;91:151-175.

Fasano A. Clin Rev Allergy Immunol. 2017;42:71-78.

RA: How Joints Get Inflamed

• Gut microbial dysbiosis and increased intestinal permeability

– Bacterial Cell Wall Components (BCWC) in the bloodstream and joints

– Example: lipopolysacharides (LPS), can be measured

• RA patients immune response against BCWC of:

– Enterobacteria: Klebsiella, Citrobacter, Proteus, Enterobacter, E. coli, Salmonella, Yersinia, Shigella, Serratia

– Intestinal gram-positive bacteria like Bacillus

Sandhya P, et al. Int J Rheum Dis. 2016;19(1): 8-20.

Factors Influencing the Gut Ecosystem

Childhood

•Breast vs. formula

•C-section

•Excessive hygiene

Lifestyle

•Chronic stress

•Poor sleep

•Physical inactivity

Food

•Processed diet

•Insufficient fiber and phytonutrients

Environment

• Exposure to toxins

• Medication

• Alcohol

• Infections

• High levels of oxidative stress associated with ALL TYPES of arthritis

• High oxidative stress markers predict relapse in people apparently in remission

• Testing is important to assess current status, follow treatment, predict relapse, and know when to taper off medication

Measuring Oxidative Stress

Testing for Oxidative Stress

These markers are included in:

and and

Oxidative Stress Markers in the NutrEval

Oxidative Stress Analysis 2.0 (Blood)

• 60 year old female

• Came to see me to help her get off her medication

– Started ISRP 3 months ago, already improved with diet change and gut treatment

• Tapering the Methotrexate (MTX) (now 15 mg/day) and Rituxan Q6 months, x2 so far

Case Study: Rheumatoid Arthritis

Timeline

1995/1997• IVF for 2 children• She’s in her 40s

1999• Hands swelled, ignored it• Working• 2 toddlers, breast feeding• Marathons

2000• STRESS and FLARE• Dad remarried, cut off• Hands, feet, wrists• Workup: RA with high RF• Needed to quit work• Rx: Plaquenil, macrobiotic diet,

no dairy, green tea• REMISSION

2002

• Symptoms returned,

added MTX + folate

• REMISSION

• RF normal

• Home with kids,

working 1 day/week

2005

• Gut issues: reflux, abdominal pain

• Endo normal

• GB U/S, ok

• Lived with it

2009

• +PPD: INH for 7 months

• Also, Levoquin on-and-off for bronchitis

Timeline (continued)

2014• STRESS and FLARE• Father and brother died• Crippled, couldn’t pick up cup• Prednisone (first time) + Embrel x 4

months (in addition to Plaquenil and MTX)

2015• Needed prednisone again for

another 4 months• WBC started dropping (still an issue)• Off Plaquenil, added Rituxan• 6 months ago/August 2015: off

prednisone and finally in REMISSION

2016

• 3 months ago had some gut

issues: gas, bloating, GERD, no

joint symptoms

• Still on MTX and Rituxan

• Read Immune System Recovery

Plan– Elimination diet for first time

ever, vegan

– Currently avoiding gluten, dairy,

sugar, wine, night shades

– Eating eggs

• Lost 10 pounds, still some

gurgling and burping

• 2 weeks later: Gut Cleanse

program

• Stay on current dose of MTX (she had just lowered it)

• Continue Gut Cleanse herbs for another month: GI MicrobX + Oregano

• UltraInflammx 360 plus shake daily

• Heartburn TX from Vital nutrients

• High dose omega oils: start with 1.5 - 2 grams EPA/DHA plus 500 mg GLA

• Inflammatone (DFH): curcumin/boswellia/enzyme blend

• Daily meditation

• Remain on the elimination diet as currently following

• History of periodontal disease: start waterpik treatment with Biocidin added

• Tests: NutrEval, routine blood work + autoimmune/RA testing, stool test later

Medical Visit #1: Plan

Supplement Program:

Initial Visit

I added:

• Gut Cleanse Packets

• Heartburn TX

• ProEFA liquid

• Inflammatone

• Biocidin to waterpik

• Feeling well• Lost 15# now since starting program 4 months ago• Gut symptoms now resolved• Still in remission, no joint pain

• Test results:

– NutrEval

• +oxidative stress• high mercury and lead• high needs for many nutrients

Medical Visit #2:

– Routine/Conventional

• CCP>250• RF 215.6• ANA neg• neutropenia

Initial NutrEval

March 2016

Test Results:

Initial NutrEval

March 2016

Test Results:

Test Results:

CBC shows low neutrophils

• Continue waterpik with Biocidin

• Increase probiotics

• Increase antioxidants: add Vitamin C, Phytoganix powder, NAC

• Look for sources of lead and limit fish

• Exercise: swimming, walking, yoga

• Daily meditation practice

• Continue Leaky Gut diet for arthritis

• Continue rest of supplements: Inflammatone, omega oils, Vitamin D, collagen complex (Osteovantiv)

Treatment Plan

Supplement Program:

2nd Visit

I added:

• Phytoganix

• Vitamin C

• CoQ10

• NAC

• Probiotic

• B Supreme

• 95% gluten and dairy free now

• Ate lots of tomatoes over the summer

• Loves Glutagenics and Inflammatone

• Overall feels better and still in remission

• Did another round of Rituxan

• Down to 6 methotrexate, tapering

• Test results:

– GI Effects• 4+ Klebsiella and 1+ Candida

• Very low Lactobacillus and Bifidobacterium in both PCR and cultures

– Routine/Conventional• ESR, CRP, hsCRP, LpPLA2, fibrinogen normal

• Low neutrophils persist

Medical Visit #3: 6 months Later (October 2016)

GI Effects

October 2016

Test Results:

GI Effects

Stool Culture

October 2016

Test Results:

• Test Results

– GI Effects: • 4+ Klebsiella and 1+ Candida

• Very low Lactobacillus and Bifidobacterium in both PCR and cultures

– Routine/Conventional blood work:• ESR, CRP, hsCRP, LpPLA2, fibrinogen normal

• Low neutrophils persist

• Treatment

– GI Microb-X 2 BID, plus oregano 2 BID for 2 months

– Increased probiotics to 100 billion

Treatment Plan

Supplement Program:

3rd Visit

I added:

• Gut dysbiosis treatment

• She didn’t want Rx for Candidaso we did 2 months of herbs

• Switched to probiotic powder for increased dosing

• Continued everything else

• SEVERE STRESS - she’s been in a flare

• Many stressful family issues

• Skin cancer on her face

• TERRIBLE FLARE - all her joints hurt within 1 month after this

• Decided to do another Rituxan treatment, which helped

• Started eating bagels - stopped supplements - went off the program

• Kitchen under construction, can’t cook

• 1 month ago, after she did the testing for this visit, started gluten free again

Medical Visit #4: 6 Months Later (April 2017)

• NutrEval

– All Oxidative stress markers are worse She did this test on 2/21, while in the middle of this flare

– Gut markers are all high

– B’s and minerals have improved

• GI Effects Comprehensive

– No harmful microbes in the cultures

– PCR: high bacteroidetes

– Beta gluc high

• SIBO + 97/0

Test Results

2nd Follow-up NutrEval

March 2017

Test Results:

Note:

• Lipid peroxides higher, was 5.6

• 8-OHDG slightly lower, was 20

• Glutathione was 926

• Mercury gone (stopped eating fish)

• Lead much improved

2nd Follow-up NutrEval

March 2017

Test Results:

Note:

• Detox markers higher

• Suggests increased oxidative stress/need for more antioxidant support

2nd Follow-up NutrEval

March 2017

Test Results:

2nd Follow-up

GI Effects

March 2017

Test Results:

SIBO Breath Test

Test Results:

• High oxidative stress markers tells us that we need to work harder to treat underlying issues

• Stress can worsen SIBO, and periodontal issues, as well as derail the food plan

• She had given up and all the underlying issues got worse again, despite being able to lower her medication

• Also, we were having underlying issues that needed to be addressed– She would talk about her stress like it was happening to a third person and without emotion

– Had a high tolerance for pain and would let things slide and ignore first warning signs

– She did not keep regular appointments and follow ups were too far apart

Assessment

• RA with high oxidative stress markers and SIBO

• Stress: major trigger

• Continue treating oral microbiome with waterpik

• Candibactin BR: continue treating the gut as source of oxidative stress

• Focus on returning to whole foods, healthy food plan: 100% gluten-free, dairy-free and nightshade-free again

• Focus on antioxidants– Add Vitamin A, Vitamin E, lipoic acid

– Remind her to take the antioxidant powder (Phytoganix); she hasn’t been doing it

– Increase Vitamin C to bowel tolerance

Treatment Plan

Supplement Program:

4th Visit

I added:

• Gut treatment with CandibactinBR/AR

• Lipoic acid

• Switched back to lower dose probiotic

• Returned after 6 months

• Her flare had subsided within 1-2 months of starting the last treatment program and she is in remission again

• Came back to check in; she was concerned that her gut was acting up again due to some reflux and bloating

• Has been mostly consistent with supplements, but stopped some of the antioxidants

• She went down to 4 MTX last week

• Rituxan was due last month (she skipped so far), but considering taking it so she can go skiing

• She didn’t do the repeat NutrEval, just brought blood work– RF 117 (214.6)

– CCP still >250

– ESR 15

Medical Visit #5: 6 Months Later (October 2017)

• Assessment: RA with high CCP, improving RF, high oxidative stress markers, and recently treated for SIBO

• Focus on gums and periodontal: sent to biologic dentist, probiotic toothpaste, evaluate for mouth breathing at night – Re-start waterpik (she hadn’t kept up with this)

• Retest for SIBO: – If positive, we will do Xifaxan

– If not, no more gut cleanse treatment for now

• Retest Oxidative Stress markers and go back on the full doses of antioxidants that were prescribed last visit

Treatment Plan

Supplement Program:

6th Visit (most recent)

I changed:

• No more gut cleanse for now

• Added Saccharomyces boulardii

• Oxidative stress markers can be followed and correlate with disease activity

• True remission is not possible while these levels are high

• Clinical symptoms might be gone, but a flare is lurking around the corner with the next stressful or traumatic event

• Look for sources of oxidative stress: gut/oral dysbiosis, toxins, infections

• Work with your patients on awareness of stress and trauma and building skills for resiliency

• Lifestyle, including food, detoxing the environment, sleep, stress, exercise, are all key to good gut health and low levels of oxidative stress

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Michael Chapman, NDModerator

Susan Blum, MDPresenter

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The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnostics. Thus, Genova Diagnostics does not accept liability for consequences of any actions taken on the basis of the information provided.

Healing ArthritisTaming the Flame by Treating Oxidative Stress Susan Blum, MD, MPH

Founder and Director, Blum Center for Health

The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnostics. Thus, Genova Diagnostics does not accept liability for consequences of any actions taken on the basis of the information provided.