Difference between revisions of "Bredesen Protocol"

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(placed note up front that we're working to update after publication of new book)
(Replaced tables of tests and ranges from 1st book with tests/values from Dr B's second book)
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'''Summary of key tests for ReCode Protocol'''
'''Summary of key tests for ReCode Protocol'''
Taken from Dr Bredesen's book '''''The End of Alzheimer's'''''  provided for quick reference, refer to the book for specific information
Taken from table 1 of Dr Bredesen's second book '''''The End of Alzheimer's Program'''''  provided for quick reference, refer to the book for specific information.  If you are following his first book, note that some of the biomarkers have changed.


{| class="wikitable sortable"
{| class="wikitable"
|+
!
!Critical Tests
!Target Values
!Comments
|-
|-
! Genetics!! Critical tests !! Target values !! Optional tests!! Comments
|'''Inflammation, protection, and vascular'''
|hs-CRP
|<0.9 mg/L
|Systemic Inflammation
|-
|-
| || ApoE || Negative for ApoE4 || Whole genome, exome, or SNPs || Saliva or blood
|
|Fasting insulin
Fasting Glucose<br>
Hemoglobin A1c<br>
HOMA-IR
|3.0-5.0 μIU/mL*<br>
70-90 mg/dL<br>
4.0-5.3%<br>
<1.2
|Glycotoxicity and insulin resistance markers<br />
*For those who are insulin sensitive, with fasting glucose <90 mg/dL, fasting insulin of < 3.0 is still a healthy range
|-
|-
|}
|
 
|Body mass index (BMI)
 
|18.5-25
 
|Weight (lbs) x 703/height (inches)<sub>2</sub>
{| class="wikitable sortable"
|-
|
|Waist to hip ratio (women)<br>
Waist to hip ratio (man)
|<0.85<br>
<0.9
|
|-
|-
! Blood Tests!! Critical tests !! Target values !! Optional tests!! Comments
|
|Homocysteine
|≤7μmol/L
|Reflects methylation, inflammation, and detox
|-
|-
| Inflammation vs. cellular protection || Hs-CRP || <0.9 mg/L|| IL-6, TNFalpha||  
|
|Vitamin B<sub>6</sub><br>
Vitamin B<sub>9</sub>(folate)<br>
Vitamin B<sub>12</sub>
|25-50 mcg/L (PP)<br>
10-25 ng-mL<br>
500-1500 pg/mL
|Improve methylation and reduce homocysteine
|-
|-
| || Homocysteine || <7  micromolar || ||  
|
|Vitamin C<br>
Vitamin D<br>
Vitamin E
|1.3-2.5 mg/dL<br>
50-80ng/mL<br>
12-20 mg/L
|
|-
|-
| || Vit. B6, B12, folate || 60-100 mcg/L (B6), 500-1500 pg/ml (B12),10-25 ng/ml (folate)|| ||
|
|Omega-6 to omega-3 ratio
|1:1 to 4:1 (beware that <0.5:1 may be associated with bleeding tendency)
|Ratio of inflammatory to anti-inflammatory omega fats
|-
|-
| || Vit. C, D, E || 1.3-2.5 (C) 50-80 (D) 12-20 (E)|| || Vit. D is measured as 25-hydroxy-cholecalciferol
|
|Omega-3 index
|≥10% (ApoE4+)<br>
8-10% (ApoE4-)
|Proportion of anti-inflammatory omega-3 fats
|-
|-
| || Omega-6: omega-3 ratio||0.5-3.0|| ||
|
|AA to EPA ratio (arachidonic acid to eicosapentaenoic acid ratio)
|<3:1
|Ratio of inflammatory AA to anti-inflammatory EPA
|-
|-
| || A/G ratio (albumin:globulin ratio)||≥  1.8 > 4.5 (albumin)
|
|| ||
|A/G ratio (albumin to globulin ratio)<br>
Albumin
|≥1.8:1<br>
4.5-5.4 g/dL
|Markers of inflammation, liver health, and amyloid clearance
|-
|-
| || Fasting insulin, glucose, hemoglobin A1c||≤ 4.5 mIU/L (fasting insulin), 70-90 mg/dL (fasting glucose), <5.6 percent (HbA1c.)
|
Although in a 2019 interview Dr Bredesen updated to: fasting insulin < 5.0, and A1c of 4.5 to 5.2.
|LDL-P<br>
||Neural exosome studies (p-tau, AB42, REST, cathepsin D, and IRS-1 phos. Ratio) ||
Small dense LDL<br>
Oxidized LDL
|700-1200nM<br>
<28 mg/dL<br>
<60 ng/mL
|LDL-P is LDL particle number
|-
|-
| || Body mass index (BMI)||18-25|| ||  
|
|Total cholesterol<br>
HDL cholesterol<br>
Triglycerides<br>
TG to HDL ratio
|150-200 mg/dL<br>
>50 mg/dL<br>
<150 mg/dL<br>
<1.1
|
|-
|-
| || LDL-p or sdLDL or oxidized LDL||700-1000 (p), <20 mg/dL or less than 20% of LDL (sd), <60 U/I (ox) || ||  
|
|CoQ10
|1.1-2.2 mcg/mL
|Affected by cholesterol level
|-
|-
| || Cholesterol, HDL, triglycerides||>150 (cholesterol) >50 (HDL) <150 (TG) || ||  
|
|Glutathione
|>250 mcg/mL (>814 μM)
|Major antioxidant and detoxicant
|-
|-
| || Glutathione||5.0-5.5 || ||  
|
|Leaky gut, leaky blood-brain barrier, gluten sensitivity, autoantibodies
|Negative
|
|-
|-
| || RBC thiamine pyrophosphate (TPP)||100-150 ng/ml of packed cells || ||  
|'''Minerals'''
|RBC-magnesium
|5.2-6.5 mg/dL
|Preferable to serum magnesium
|-
|-
| || Leaky gut, leaky bloodbrain barrier, gluten sensitivity, autoantibodies||Negative || ||  
|
|Copper
|90-110 mcg/dL
|
|-
|-
|}
|
 
|Zinc
 
|90-110 mcg/dL
 
|
 
{| class="wikitable sortable"
|-
|-
! Trophic support!! Critical tests !! Target values !! Optional tests!! Comments
|
|Selenium
|110-150-ng/mL
|
|-
|-
| || Vit D.|| 50-80|| ||  
|
|Potassium
|4.5-5.5 mEq/L
|
|-
|-
| || Estradiol (E2), progesterone (p) || 50-250 pg/ml (E2), 1-20 ng/ml (p)|| ||
|'''Trophic Support'''
|Vitamin D
|50-80 ng/mL
|(250H-D3)
|-
|-
| || Pregnenolone, cortisol, DHEA-sulfate || 50-100 ng/dL (preg), 10-18 mcg/dL (cort) 350-430 mcg/dL (DHEA, women), 400-500 mcg/dL (DHEA, men)|| ||  
|
|Estradiol<br>
Progesterone
|50-250 pg/mL<br>
1-20 ng/dL (P)
|Women; age dependent
|-
|-
| || Testosterone, free testosterone || 500-1000 ng/dl, 6.5-15 ng/dL (free)|| ||  
|
|Pregnenolone<br>
Cortisol (AM)<br>
DHEA-S (women)<br>
DHEA-S (men)
|100-250 ng/dL<br>
10-18 mcg/dL<br>
100-380 mcg/dL<br>
150-500 mcg/dL
|Age dependent
|-
|-
| || Free T3, free T4, reverse T3, TSH || 3.2-4.2 pg/ml (fT3) 1.3-1.8 (fT4) <20 ng/dL (rT3) <2.0 microIU/ml (TSH) Ft3:rt3 ≥20|| ||  
|
|Testosterone<br>
Free Testosterone
|500-1000 ng/dL<br>
18-26 pg/ml
|Men; age dependent
|-
|-
|}
|
 
|Free T3<br>
 
Free T4<br>
 
Reverse T3<br>
{| class="wikitable sortable"
TSH<br>
Free T3 to reverse T3<br>
Anti-thyroglobulin antibodies<br>
Anti-TPO
|3.2-4.2 pg/mL<br>
1.3-1.8 ng/dL<br>
<20 ng/dL<br>
<2.0 mIU/L<br>
>0.02:1<br>
Negative<br>
Negative
|
|-
|-
! Toxin related!! Critical tests !! Target values !! Optional tests!! Comments
|'''Toxin-related'''
|Mercury<br>
Lead<br>
Arsenic<br>
Cadmium
|<5 mcg/L<br>
<2 mcg/dL<br>
<7 mcg/L<br>
<2.5 mcg/dL
|Heavy Metals
|-
|-
| || Mercury, lead, arsenic, cadmium || <5, <2, <7, <2.5, respectively ||<50th percentile (Quicksilver) ||  
|
|Mercury Tri-Test
|<50th percentile
|Hair, blood, urine
|-
|-
| || Copper:zinc ratio ||0.8-1.2|| RBC zinc; ceruloplasmin ||
|
|Organic toxins (urine)
|Negative
|Benzene, toluene, etc.
|-
|-
| || C4a, TGF-B1, MSH ||<2830 (C4a) <2380 (TGF-B1) 35-81 (MSH)|| MMP9, VEGF, leptin, VIP, ADH, osmolality || If abnormal, add MARCoNS culture and VCS testing
|
|Glyphosate (urine)  
|<1.0 mcg/g creatinine
|Herbicide
|-
|-
| || HLA-DR/DQ || Benign HLA-DR/DQ || ||  
|
|Copper to zinc ratio
|0.8-1.2.1
|Higher ratios associated with dementia
|-
|-
|}
|
 
|C4a<br>
 
TGF-β1<br>
{| class="wikitable sortable"
MMP-9<br>
MSH
|<2830 ng/mL<br>
<2380 pg/mL<br>
85-332 ng/mL<br>
35-81 pg/mL
|Associated with inflammatory response
|-
|-
! Metals Excluding those listed above!! Critical tests !! Target values !! Optional tests!! Comments
|
|Urinary mycotoxins
|Negative
|May include contributions from inhalation, ingestion, and infection
|-
|-
| || RBC-magnesium || 5.2-6.5 mg/dL|| ||
|
|BUN<br>
Creatinine
|<20 mg/dL<br>
<1.0 mg/dL
|Reflects kidney function
|-
|-
| || Copper, zinc ||90-110 mcg/dL (both)|| ||  
|
|AST<br>
ALT
|<25 U/L<br>
<25 U/L
|Reflects liver damage
|-
|-
| || Selenium ||110-150  ng/ml|| ||  
|
|VCS (visual contrast sensitivity)
|Pass
|Failure associated with biotoxin exposure
|-
|-
| || Potassium || 4.5-5.5|| ||  
|
|ERMI test
|<2
|Mold index from building
|-
|-
| || Calcium || 8.5-10.5|| ||  
|
|HERTSMI-2 test
|<11
|Index of most toxic molds
|-
|-
|}
|'''Pathogen-related'''
 
|CD57
 
|60-360 cells/μL
{| class="wikitable sortable"
|Reduced with Lyme
|-
|-
! Cognitive performance!! Critical tests !! Target values !! Optional tests!! Comments
|
|MARCoNS
|Negative
|
|-
|-
| || CNS Vital Signs, BrainHQ, or equivalent || >50th percentile for age, improving w/ practice || Novel object recognition ||
|
|Antibodies to tick-borne pathogens
|Negative
|Borrelia, Babesia, Bartonella, Ehrlichia, Anaplasma
|-
|-
|}
|
 
|Antibodies to Herpes family viruses
 
|Negative
{| class="wikitable sortable"
|HSV-1, HSV-2, HHV-6, VZV, EBV, CMV
|-
|-
! Imaging!! Critical tests !! Target values !! Optional tests!! Comments
|'''Neurophysiology'''
|Peak alpha frequency on quantitative EEG
|8.9-11 Hz
|Slows with cognitive decline; useful for following progress
|-
|-
| || MRI w/ volumetrics || Hippocampal, cortical valume percentiles steady (or increasing) for age, >25th  percentile || ||
|
|P300b on evoked response testing
|<450 ms
|Delayed with cognitive decline; useful for following progress
|-
|-
|}
|'''Other Tests'''
 
|MoCA (Montreal Cognitive Assessment)
 
|28-30
{| class="wikitable sortable"
|
|-
|-
! Sleep!! Critical tests !! Target values !! Optional tests!! Comments
|
|Nocturnal oxygen saturation (SpO<small>2</small>)
|96-98%
|Affected by living at high altitude
|-
|-
| || Sleep study || AHI <5/h || ||  
|
|AHI (apnea-hypopnea index)
|<5 events per hour
|>5 indicates sleep apnea
|-
|-
|}
|
 
|Oral DNA
 
|Negative for pathogens
{| class="wikitable sortable"
|P. gingivalis, T. denticola, etc.
|-
|-
! Microbiomes!! Critical tests !! Target values !! Optional tests!! Comments
|
|Stool analysis
|No pathogens or dysbiosis
|
|-
|-
| || Gut, oral, nasal || No pathogens || ||  
|
|ImmuKnow (CD4 function, indicated by ATP production)
|≥525 ng/mL
|Indicates function of helper cells of the cellular arm of adaptive immune system
|-
|-
|}
|}

Revision as of 15:04, 20 August 2020

Introduction

Note that with the publication of Dr Bredesen's 2nd book, The End of Alzheimer's Program, published on August 18, 2020, some of the information in this Wiki, specifically with regard to biomarkers and their target values, may have been superseded. An update is in the works, please bear with us as we work to update.


Dr. Dale Bredesen has created the ReCODE protocol that involves multiple strategies to address specific health issues that contribute to Alzheimer's Disease (AD). The results of each strategy are measured by using blood tests, cognitive evaluations, and other markers of overall health improvements. Actions are tweaked over time to aim for optimal lab and evaluation results. His analogy is to think of AD as a leaky roof - there are as many as 36 leaks in the AD roof that need to be addressed to stop the problem. Not every patient will have the same leaks, and the protocol is customized based on the patient’s genetics, current health, and lifestyle.

In 2014, his first published paper on the protocol, Reversal of Cognitive Decline, highlighted 10 case studies. Of those 10 people, nine showed enough improvement to return to normal life activities. Several hundred people with cognitive impairment have since followed the protocol, and most have seen a reversal of cognitive impairment. He published results of reversing various levels of cognitive decline in Reversal of Cognitive Decline: 100 patients, published October 2018. His book The End of Alzheimer's, published August 2017 discusses his protocol and explains many of the mechanisms of Alzheimer's.

Bredesen’s protocol has not been tested as a preventative, however in a May 2019 podcast interview, Dr Bredesen did say that he’s never had someone at risk come in for prevention and develop even mild cognitive impairment. Research has shown that amyloid-β is deposited in E4 carriers as early as their thirties, so addressing components prior to experiencing cognitive impairment symptoms will likely lead to better health and cognition in aging. Members on the APOE4.Info forum who follow the protocol report improvements not only in health but also in cognition, even if they do not have an SCI or MCI diagnosis.

Although Bredesen does not see private patients, he has made his protocol available to those seeking doctor assistance through AHNP: Precision Health. MPI Cognition, his previous affiliation, was acquired by AHNP and his prior affiliation with Muses Labs has ended.


The following list links to summaries of why each strategy is important, what you can do, and a selection of research references.

Diet Strategies

Optimize diet

Enhance autophagy and ketogenesis

Improve GI Health


Lifestyle Strategies

Reduce stress

Optimize sleep

Exercise

Rule out sleep apnea

Optimize mitochondrial function


Lab Tests to Track and Treat

Homocysteine

B vitamins

Inflammation

Insulin sensitivity (insulin and blood glucose)

Hormones

Zn:fCu ratio

Vitamin D

Rule out heavy metal toxicity

Optimize antioxidants  ??


Brain Strategies

Brain stimulation

Reduction of Aß

Cognitive enhancement

Increase NGF

Provide synaptic structural components

Increase focus

Increase SirT1 function


Inhalational Alzheimer's (editing note: update to types of AD)


Resources

Lab tests: Lab testing information


Supplements: Supplement ordering


Tracking results: Our member "optimize" made a Google spreadsheet using the recommended Cognoscopy test values in The End of Alzheimer's. This spreadsheet is a simple table to help you track your latest test results, with values flagged as "high", "low", or "in range". It's intended as a quick way to organize test results, and see at a glance where to make improvements.

The link to make your own copy of the spreadsheet for your private use is here: https://goo.gl/8t2dxi

Please note! The copied spreadsheet will let you type in the white areas, but this may cause errors in the formulas. If you accidentally type in a white area, hit "ctrl-Z" a few times to remove the typing, or download a fresh copy of the spreadsheet.


Summary of key tests for ReCode Protocol Taken from table 1 of Dr Bredesen's second book The End of Alzheimer's Program provided for quick reference, refer to the book for specific information. If you are following his first book, note that some of the biomarkers have changed.

Critical Tests Target Values Comments
Inflammation, protection, and vascular hs-CRP <0.9 mg/L Systemic Inflammation
Fasting insulin

Fasting Glucose
Hemoglobin A1c
HOMA-IR

3.0-5.0 μIU/mL*

70-90 mg/dL
4.0-5.3%
<1.2

Glycotoxicity and insulin resistance markers
*For those who are insulin sensitive, with fasting glucose <90 mg/dL, fasting insulin of < 3.0 is still a healthy range
Body mass index (BMI) 18.5-25 Weight (lbs) x 703/height (inches)2
Waist to hip ratio (women)

Waist to hip ratio (man)

<0.85

<0.9

Homocysteine ≤7μmol/L Reflects methylation, inflammation, and detox
Vitamin B6

Vitamin B9(folate)
Vitamin B12

25-50 mcg/L (PP)

10-25 ng-mL
500-1500 pg/mL

Improve methylation and reduce homocysteine
Vitamin C

Vitamin D
Vitamin E

1.3-2.5 mg/dL

50-80ng/mL
12-20 mg/L

Omega-6 to omega-3 ratio 1:1 to 4:1 (beware that <0.5:1 may be associated with bleeding tendency) Ratio of inflammatory to anti-inflammatory omega fats
Omega-3 index ≥10% (ApoE4+)

8-10% (ApoE4-)

Proportion of anti-inflammatory omega-3 fats
AA to EPA ratio (arachidonic acid to eicosapentaenoic acid ratio) <3:1 Ratio of inflammatory AA to anti-inflammatory EPA
A/G ratio (albumin to globulin ratio)

Albumin

≥1.8:1

4.5-5.4 g/dL

Markers of inflammation, liver health, and amyloid clearance
LDL-P

Small dense LDL
Oxidized LDL

700-1200nM

<28 mg/dL
<60 ng/mL

LDL-P is LDL particle number
Total cholesterol

HDL cholesterol
Triglycerides
TG to HDL ratio

150-200 mg/dL

>50 mg/dL
<150 mg/dL
<1.1

CoQ10 1.1-2.2 mcg/mL Affected by cholesterol level
Glutathione >250 mcg/mL (>814 μM) Major antioxidant and detoxicant
Leaky gut, leaky blood-brain barrier, gluten sensitivity, autoantibodies Negative
Minerals RBC-magnesium 5.2-6.5 mg/dL Preferable to serum magnesium
Copper 90-110 mcg/dL
Zinc 90-110 mcg/dL
Selenium 110-150-ng/mL
Potassium 4.5-5.5 mEq/L
Trophic Support Vitamin D 50-80 ng/mL (250H-D3)
Estradiol

Progesterone

50-250 pg/mL

1-20 ng/dL (P)

Women; age dependent
Pregnenolone

Cortisol (AM)
DHEA-S (women)
DHEA-S (men)

100-250 ng/dL

10-18 mcg/dL
100-380 mcg/dL
150-500 mcg/dL

Age dependent
Testosterone

Free Testosterone

500-1000 ng/dL

18-26 pg/ml

Men; age dependent
Free T3

Free T4
Reverse T3
TSH
Free T3 to reverse T3
Anti-thyroglobulin antibodies
Anti-TPO

3.2-4.2 pg/mL

1.3-1.8 ng/dL
<20 ng/dL
<2.0 mIU/L
>0.02:1
Negative
Negative

Toxin-related Mercury

Lead
Arsenic
Cadmium

<5 mcg/L

<2 mcg/dL
<7 mcg/L
<2.5 mcg/dL

Heavy Metals
Mercury Tri-Test <50th percentile Hair, blood, urine
Organic toxins (urine) Negative Benzene, toluene, etc.
Glyphosate (urine) <1.0 mcg/g creatinine Herbicide
Copper to zinc ratio 0.8-1.2.1 Higher ratios associated with dementia
C4a

TGF-β1
MMP-9
MSH

<2830 ng/mL

<2380 pg/mL
85-332 ng/mL
35-81 pg/mL

Associated with inflammatory response
Urinary mycotoxins Negative May include contributions from inhalation, ingestion, and infection
BUN

Creatinine

<20 mg/dL

<1.0 mg/dL

Reflects kidney function
AST

ALT

<25 U/L

<25 U/L

Reflects liver damage
VCS (visual contrast sensitivity) Pass Failure associated with biotoxin exposure
ERMI test <2 Mold index from building
HERTSMI-2 test <11 Index of most toxic molds
Pathogen-related CD57 60-360 cells/μL Reduced with Lyme
MARCoNS Negative
Antibodies to tick-borne pathogens Negative Borrelia, Babesia, Bartonella, Ehrlichia, Anaplasma
Antibodies to Herpes family viruses Negative HSV-1, HSV-2, HHV-6, VZV, EBV, CMV
Neurophysiology Peak alpha frequency on quantitative EEG 8.9-11 Hz Slows with cognitive decline; useful for following progress
P300b on evoked response testing <450 ms Delayed with cognitive decline; useful for following progress
Other Tests MoCA (Montreal Cognitive Assessment) 28-30
Nocturnal oxygen saturation (SpO2) 96-98% Affected by living at high altitude
AHI (apnea-hypopnea index) <5 events per hour >5 indicates sleep apnea
Oral DNA Negative for pathogens P. gingivalis, T. denticola, etc.
Stool analysis No pathogens or dysbiosis
ImmuKnow (CD4 function, indicated by ATP production) ≥525 ng/mL Indicates function of helper cells of the cellular arm of adaptive immune system

Dr Bredesen's research

Book

Dr Bredesen's book, The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline, published August 22, 2017. Amazon link to Dr Bredesen's book

Videos and interviews

  • He cites 6 types of Alzheimer's: (1) inflammatory (2) atrophic (1.5) glycotoxic (3) toxic (4) vascular and (5) traumatic. Vascular and traumatic are new since publication of his book
  • In his markers for glycotoxicity, he cites fasted insulin of 5.0 (his book cites 4.5) or lower and HbA1c 4.5 to 5.2 (the book cites less than 5.6)
  • Dr Bredesen said that the Big Four to avoid are: grains, simple carbs, dairy, and lectins. Pro-inflammatory lectins have been added since publication of his book.
  • He added another mold/mycotoxin to his list: Wallemia. The big 5 molds are now: Stachybotrys, Aspergillus, Penicillium, Chaetomium, and Wallemia.


Dr Bredesen's Papers

  • The first version of Dr Bredesen’s protocol (which is similar to the above) can be found in his paper: Reversal of cognitive decline: A novel therapeutic program, published September 2014, https://www.ncbi.nlm.nih.gov/pubmed/25324467

Subsequent papers of Dr Bredesen do not address his protocol, but further examine his findings. They include:

This paper addresses the common criticism that the original paper only covered a small number of patients. This paper documents improvement in cognition of 100 patients treated by several different physicians thus providing further support for a randomized, controlled clinical trial of the protocol and overall approach:

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