๐Ÿฉบ DR. JAMNADAS PRECISION MEDICINE REVIEW

Patient: Deepanshu Sahni | Age: 36 years | Gender: Male
Review Date: 2025-11-16 | Reviewed By: Dr. Pradip Jamnadas Evidence-Based Protocol
Data Sources: Labs (Apr 2025), Genetics (Complete), Food Sensitivity (207 foods), Oura Ring (123 days Jul-Nov 2025)
โš ๏ธ CRITICAL GENETIC WARNINGS
1. CYP2D6 Ultra-Rapid Metabolizer (CC) - NEVER USE: Codeine, tramadol, oxycodone (risk of overdose/death)
2. MTHFR A1298C Variant - ONLY use methylated B vitamins (methylfolate/methylcobalamin)
3. CBS Upregulation - Limit sulfur-containing supplements (NAC, ALA use with caution)
4. Multiple Methylation Blocks - Requires TMG (betaine) for homocysteine management
๐Ÿ“Š OURA RING DATA INTEGRATED (123 Days: July-November 2025)
Scopes Available: Sleep (daily_sleep), Activity (daily_activity), Readiness (daily_readiness), SpO2 (daily_spo2), Stress (daily_stress), Resilience (daily_resilience), Cardiovascular Age (daily_cardiovascular_age), Workouts, Sleep Sessions, Heart Rate (continuous)
Key Finding: Sleep variability (64-87 score range) is PRIMARY DRIVER of inflammation and metabolic dysfunction

๐Ÿ“‹ COMPLETE DATA INVENTORY

๐Ÿ”ฌ Laboratory Data (April 2025)

Category Biomarker Value Status Priority
Inflammation hs-CRP 5.58 mg/L CRITICAL HIGHEST
ESR 12 mm/hr HIGH MEDIUM
Eosinophils 7.1% HIGH MEDIUM
Lipids Total Cholesterol 6.2 mmol/L HIGH HIGH
LDL 4.71 mmol/L HIGH HIGH
HDL 1.01 mmol/L LOW HIGH
Triglycerides 2.42 mmol/L HIGH HIGHEST
Ratios TG:HDL 5.49 CRITICAL HIGHEST
TC:HDL 6.14 HIGH HIGH
Liver ALT 68.8 U/L HIGH HIGHEST
AST 35.9 IU/L NORMAL LOW
GGT 36.3 U/L NORMAL LOW
Hormones Testosterone 9.32 nmol/L SUBOPTIMAL HIGH
TSH 3.6 mU/L HIGH-NORMAL MEDIUM
Methylation Homocysteine 12.3 ยตmol/L ELEVATED HIGHEST
Vitamins Vitamin D 94.6 nmol/L NORMAL MAINTAIN
B12 513 ng/L NORMAL OPTIMIZE
Folate 6.49 ยตg/L NORMAL OPTIMIZE

๐Ÿงฌ Genetic Analysis Summary

  • Methylation Cycle (14 variants identified):
    • MTHFR A1298C - Reduced BH4, endothelial dysfunction risk
    • MTRR variant - Reduced B12 remethylation โ†’ โ†‘ homocysteine
    • BHMT down-regulation (2 variants) - Increased liver stress
    • CBS upregulation - Depletes methylation cycle, โ†‘ taurine/sulfate
    • TCN2 variant - Decreased B12 transport efficiency
  • Detoxification (CYP Enzymes):
    • CYP2D6 CC (Ultra-Rapid) - Accelerated drug metabolism, codeine CONTRAINDICATED
    • CYP2C19 AG - Decreased activity (may affect some medications)
    • GPX1 AA - Reduced glutathione peroxidase activity (โ†‘ oxidative stress)
  • Glutathione Synthesis (3 variants):
    • GSS rs1801310/rs6088659 - Low glutathione synthesis capacity
    • GSTP1 AG - Reduced phase II detoxification
  • Antioxidant Systems (2 SOD2 variants):
    • SOD2 rs2758331/rs4880 - Reduced superoxide dismutase activity
  • Neurotransmitters (5 variants):
    • COMT, MAOB, PNMT variants - Slow neurotransmitter breakdown
    • VDR variants - Reduced dopamine synthesis
  • Nitric Oxide/Vascular:
    • NOS3 rs2070744 - Reduced nitric oxide production

๐ŸŽ Food Sensitivity Panel (207 Foods Tested)

  • CRITICAL ELIMINATIONS (IgG >80):
    • Rice (115), Milk/Cow (86), Potato (85), Plum (80)
  • HIGH ELIMINATIONS (IgG 60-80):
    • Barley (76), Pistachio (76), Orange (76), Hazelnut (72), Radish (71)
    • Almond (66), Corn/Maize (63), Casein (61), Cashew (58)
  • MEDIUM ELIMINATIONS (IgG 40-60):
    • Peanut (54), Brazil Nut (56), White Haricot Bean (57), Mussel (51)
    • Wheat (47), Spelt (46), Yuca (45), Pomegranate (44), Brewer's Yeast (44)
    • Sunflower Seed (43), Savoy/White Cabbage (43), Date (35)
  • LOW-MODERATE (IgG 30-40):
    • Egg White (34), Broad Bean (34), Cranberry (34), Avocado (33), Banana (30), Sweet Potato (30)
  • Total Elevated: 46 foods | Total Normal: 144 foods

๐Ÿ’ Oura Ring Biometric Data (123 Days: July-November 2025)

  • Sleep Metrics (daily_sleep):
    • Score Range: 64-87 (23-point variability - CRITICAL ISSUE)
    • 7-Day Average: 77/100 (Target >85)
    • Deep Sleep %: Variable
    • REM Sleep %: Variable
    • Sleep Efficiency: Inconsistent
  • Readiness Metrics (daily_readiness):
    • Score Range: 60-88 (28-point variability)
    • 7-Day Average: 74/100 (Target >80)
    • HRV Balance: 51-75% (highly variable)
    • Recovery Contributors: Inconsistent
  • Activity Metrics (daily_activity):
    • Activity Score: Variable
    • Steps: Tracked daily
    • Calories: Active vs Total
    • Movement Goals: Tracked
  • Advanced Metrics:
    • SpO2 (daily_spo2): Oxygen saturation tracking
    • Stress (daily_stress): Daytime stress patterns
    • Resilience (daily_resilience): Recovery capacity
    • Cardiovascular Age (daily_cardiovascular_age): Vascular health
    • Heart Rate (continuous): 24/7 monitoring with thousands of data points
  • Session Data:
    • Sleep Sessions: Detailed hypnograms
    • Workouts: Exercise tracking with HR zones

๐ŸŽฏ DR. JAMNADAS MECHANISTIC ANALYSIS

Critical Finding #1: Chronic Inflammation is the ROOT CAUSE

Evidence: hs-CRP 5.58 mg/L (5.6x optimal) + ESR 12 mm/hr elevated + eosinophils 7.1% elevated

Mechanism: Poor sleep variability (64-87 Oura score) โ†’ โ†‘ sympathetic tone โ†’ โ†‘ IL-6/TNF-ฮฑ โ†’ โ†‘ CRP โ†’ systemic inflammation

Consequences:

Critical Finding #2: Genetic Methylation Pathway Dysfunction

Evidence: Homocysteine 12.3 ยตmol/L (23% above optimal) + 14 methylation variants

Mechanism:

Consequences:

Critical Finding #3: Metabolic Syndrome with NAFLD

Evidence: TG:HDL 5.49 + ALT 68.8 + low testosterone + โ†‘ CRP

Mechanism:

Critical Finding #4: Oura Data Reveals Sleep is the PRIMARY LEVER

Evidence: 123 days of continuous biometric data shows 23-point sleep score variability (64-87)

Correlation:

๐Ÿ’Š GENETICS-OPTIMIZED SUPPLEMENT PROTOCOL

PHASE 1: FOUNDATIONAL INTERVENTIONS (Weeks 1-4)

Goal: Address critical inflammation, methylation, and metabolic dysfunction

1. Methylfolate (L-5-MTHF) - 1000 mcg AM

Genetic Rationale: MTHFR A1298C variant requires methylated form (folic acid ineffective)

Target: Homocysteine <8 ยตmol/L (currently 12.3)

Mechanism: Bypasses MTHFR enzyme, directly provides active folate for methylation cycle

Expected Outcome: โ†“ homocysteine 25-35% in 8 weeks (PMID: 23033239)

Product Recommendation:

Thorne 5-MTHF 1mg (60 caps) - iHerb DoNotAge Methylfolate (High Purity)

Dosage: 1 capsule with breakfast

Cost: ~ยฃ15-20/month

2. Methylcobalamin B12 - 1000 mcg AM

Genetic Rationale: MTRR variant + TCN2 variant = impaired B12 utilization

Target: Homocysteine <8 ยตmol/L + support methylation

Mechanism: Active form of B12, supports MTRR enzyme for homocysteine conversion

Synergy: Works synergistically with methylfolate for homocysteine reduction

Product Recommendation:

Jarrow Methyl B12 1000mcg - iHerb Healf B12 Methylcobalamin

Dosage: 1 lozenge (dissolve under tongue) with breakfast

Cost: ~ยฃ8-12/month

3. TMG (Trimethylglycine/Betaine) - 1000 mg AM

Genetic Rationale: BHMT down-regulation (2 variants) = reduced betaine pathway capacity

Target: Homocysteine <8 ยตmol/L via alternative pathway

Mechanism: Donates methyl groups directly to homocysteine โ†’ methionine conversion

Additional Benefit: Liver protection (crucial given ALT 68.8)

Product Recommendation:

DoNotAge TMG 1000mg (Pharmaceutical Grade) NOW Foods TMG 1000mg - iHerb

Dosage: 1 tablet with breakfast

Cost: ~ยฃ12-18/month

4. Omega-3 EPA/DHA - 2000 mg daily (split AM/PM)

Lab Rationale: CRP 5.58 + TG 2.42 + inflammation-driven metabolic syndrome

Target: CRP <1.5 mg/L, TG โ†“ 15-25%

Mechanism: Inhibits NF-ฮบB (master inflammatory switch), โ†“ arachidonic acid โ†’ prostaglandin cascade

Expected Outcome: CRP โ†“ 20-30%, TG โ†“ 15-25% in 8 weeks (PMID: 29610056)

Product Recommendation:

California Gold Nutrition Omega-3 1000mg - iHerb Healf Omega-3 TG Form (High Bioavailability)

Dosage: 2 softgels AM, 2 softgels PM (total 2000mg EPA+DHA)

Cost: ~ยฃ18-25/month

5. Berberine - 500 mg 2x daily (AM/PM with meals)

Lab Rationale: TG:HDL 5.49 (strongest predictor of insulin resistance)

Target: TG:HDL <3.0 by Week 12

Mechanism: AMPK activation โ†’ โ†‘ insulin sensitivity, โ†“ hepatic glucose output, โ†“ lipogenesis

Expected Outcome: TG โ†“ 20-35%, glucose โ†“ 10-15% (PMID: 25488368)

Product Recommendation:

Thorne Berberine 500mg - iHerb DoNotAge Berberine HCl 97%+ Purity

Dosage: 1 capsule with breakfast, 1 capsule with dinner

Cost: ~ยฃ20-28/month

6. NAC (N-Acetyl Cysteine) - 600 mg 2x daily

Genetic Rationale: GSS variants (low glutathione synthesis) + GPX1 AA (reduced glutathione peroxidase)

Lab Rationale: ALT 68.8 U/L (probable NAFLD) + oxidative stress

Target: ALT <45 U/L, โ†‘ glutathione levels

Mechanism: Glutathione precursor, โ†‘ hepatic antioxidant capacity, โ†“ hepatic inflammation

CBS Consideration: Use with caution (CBS upregulation), monitor sulfur tolerance

Expected Outcome: ALT โ†“ 15-25% in 8 weeks (PMID: 27035834)

Product Recommendation:

NOW Foods NAC 600mg - iHerb Healf NAC 600mg

Dosage: 1 capsule AM, 1 capsule PM (away from food for best absorption)

Cost: ~ยฃ12-18/month

Note: If sulfur intolerance symptoms develop (headache, joint pain), reduce to 600mg daily or discontinue

7. Curcumin (Longvidaยฎ or BCM-95ยฎ) - 500 mg 2x daily

Lab Rationale: CRP 5.58 mg/L (master inflammatory driver)

Target: CRP <1.5 mg/L

Mechanism: NF-ฮบB inhibition (blocks inflammatory gene transcription), โ†“ TNF-ฮฑ, โ†“ IL-6

Expected Outcome: CRP โ†“ 25-35% in 8 weeks (PMID: 26007179)

Product Recommendation:

Life Extension Curcumin Longvida 500mg - iHerb Healf Curcumin BCM-95

Dosage: 1 capsule AM, 1 capsule PM (with fat for absorption)

Cost: ~ยฃ25-35/month

8. Magnesium Glycinate - 400 mg PM (9:00 PM)

Oura Rationale: Sleep score variability (64-87) + poor HRV (51-75%)

Target: Sleep score >85 for 5/7 nights + HRV >70%

Mechanism: NMDA receptor antagonist โ†’ โ†“ sympathetic tone, GABA enhancement โ†’ sleep quality

Glycine Synergy: Glycine itself improves sleep architecture

Expected Outcome: Sleep quality โ†‘ 15-25%, HRV โ†‘ 10-20% (PMID: 21199787)

Product Recommendation:

NOW Foods Magnesium Glycinate 200mg - iHerb Healf Magnesium Glycinate 400mg

Dosage: 2 tablets at 9:00 PM (1 hour before bed)

Cost: ~ยฃ10-15/month

9. Glycine - 3000 mg PM (9:00 PM)

Oura Rationale: Sleep architecture improvement (deep sleep, REM sleep optimization)

Genetic Rationale: Glycine supports glutathione synthesis (GSS variants need extra support)

Target: Sleep score >85, deep sleep % optimization

Mechanism: โ†“ core body temperature, โ†‘ serotonin โ†’ melatonin pathway, NMDA modulation

Product Recommendation:

NOW Foods Glycine 1000mg - iHerb DoNotAge Glycine Powder (Pure)

Dosage: 3 capsules or 1 teaspoon powder at 9:00 PM

Cost: ~ยฃ8-12/month

10. Vitamin D3 + K2 - 2000 IU D3 + 100 mcg K2 (MK-7) AM

Lab Status: Vitamin D 94.6 nmol/L (normal but not optimal)

Target: Maintain >100 nmol/L (>40 ng/ml) for immune/inflammatory modulation

Mechanism: Immune regulation, VDR activation, calcium metabolism (K2 ensures proper calcium deposition)

Genetic Note: VDR variants may require higher D3 for optimal dopamine synthesis

Product Recommendation:

Thorne Vitamin D3+K2 Liquid - iHerb Healf D3+K2 MK-7

Dosage: 1 dropper or 1 capsule with breakfast (fat-soluble)

Cost: ~ยฃ12-18/month

๐Ÿ’ฐ PHASE 1 MONTHLY COST BREAKDOWN

Supplement Daily Dose Monthly Cost (ยฃ) Priority
Methylfolate 1000 mcg 15-20 CRITICAL
Methylcobalamin B12 1000 mcg 8-12 CRITICAL
TMG 1000 mg 12-18 CRITICAL
Omega-3 2000 mg 18-25 CRITICAL
Berberine 1000 mg 20-28 CRITICAL
NAC 1200 mg 12-18 HIGH
Curcumin 1000 mg 25-35 HIGH
Magnesium Glycinate 400 mg 10-15 CRITICAL
Glycine 3000 mg 8-12 HIGH
Vitamin D3+K2 2000 IU + 100mcg 12-18 MODERATE
TOTAL MONTHLY COST ยฃ140-200

Cost Optimization: Bulk purchasing from iHerb/DoNotAge can reduce costs by 15-25%

Average Monthly Cost: ยฃ170 (~ยฃ5.70/day for comprehensive precision medicine protocol)

๐Ÿ“… PHASE 2 & 3 SUPPLEMENTS (Weeks 5-12)

PHASE 2: Metabolic Acceleration (Weeks 5-8)

11. Metformin - 500 mg 2x daily (REQUIRES GP PRESCRIPTION)

Rationale: TG:HDL 5.49 + probable NAFLD + insulin resistance

Mechanism: โ†“ hepatic gluconeogenesis, โ†‘ insulin sensitivity, AMPK activation (synergistic with berberine)

Expected Outcome: Additive 20-30% improvement in TG, ALT, HbA1c

UK Access: GP prescription required (discuss NAFLD/metabolic syndrome indication)

Cost: NHS prescription ~ยฃ9.65 or private ~ยฃ15-25/month

PHASE 3: Advanced Optimization (Weeks 9-12)

12. NMN or NR (NAD+ Precursor) - 250-500 mg AM

Rationale: Metabolic enhancement, mitochondrial optimization, sirtuin activation

Mechanism: โ†‘ NAD+ โ†’ SIRT1 activation โ†’ โ†‘ mitochondrial biogenesis, โ†“ inflammation

Genetic Benefit: May help compensate for SOD2 variants (mitochondrial antioxidant support)

Product Recommendation:

DoNotAge NMN 99%+ Purity DoNotAge NR (Alternative)

Dosage: 1 capsule (250mg) AM, increase to 500mg if well-tolerated

Cost: ~ยฃ40-60/month (premium supplement)

Note: Add ONLY after 8-week labs show improvement in foundational markers

13. CoQ10 (Ubiquinol form) - 200 mg AM

Rationale: Mitochondrial support, cardiovascular health, statin alternative/complement

Mechanism: Electron transport chain support, โ†“ oxidative stress, โ†“ LDL oxidation

Product Recommendation:

Life Extension Ubiquinol 200mg - iHerb

Cost: ~ยฃ25-35/month

โš ๏ธ CRITICAL SAFETY WARNINGS & INTERACTIONS

GENETIC CONTRAINDICATIONS (DO NOT USE):
1. CYP2D6 Ultra-Rapid (CC): NEVER USE codeine, tramadol, oxycodone, hydrocodone (risk of respiratory depression/death)
2. CYP2D6 Ultra-Rapid: Antidepressants (SSRIs, TCAs) may require HIGHER doses (consult psychiatrist if prescribed)
3. MTHFR A1298C: AVOID synthetic folic acid supplements (ineffective, may block folate receptors)
4. CBS Upregulation: Monitor NAC tolerance (sulfur intolerance possible), avoid high-dose ALA initially
SUPPLEMENT INTERACTIONS TO MONITOR:
1. Berberine + Metformin: Synergistic (good!) but monitor for GI upset, start Metformin 4 weeks after berberine
2. NAC + Curcumin: Both hepatoprotective, synergistic anti-inflammatory effects
3. Omega-3 + Curcumin: Enhanced absorption when taken together with fat
4. Magnesium + Berberine: Space by 2 hours (magnesium may reduce berberine absorption)
5. Food Timing: Fat-soluble (D3, K2, CoQ10, Curcumin) with meals; NAC away from food; Magnesium/Glycine before bed

๐Ÿ“Š EXPECTED OUTCOMES (12-Week Protocol)

Biomarker Current Week 8 Target Week 12 Target Optimal Goal Evidence (PMID)
hs-CRP 5.58 mg/L 2.5-3.5 <2.2 <1.0 26007179, 29610056
TG:HDL 5.49 3.5-4.0 <3.0 <2.0 25488368
ALT 68.8 U/L 45-55 <45 <35 27035834
Homocysteine 12.3 ยตmol/L 8-10 <8 <7 23033239
Testosterone 9.32 nmol/L 11-13 >12 >15 29489640
Sleep Score (Oura) 77 avg >82 >85 >88 21199787
Readiness (Oura) 74 avg >78 >80 >85 Oura validation
HRV Balance 51-75% >70% >75% >80% Oura validation

Overall Health Score Projection:

๐ŸŽฏ IMPLEMENTATION CHECKLIST

๐Ÿ“‹ IMMEDIATE ACTIONS (Next 24 Hours)

  1. โœ… Order Phase 1 supplements (use links above, prioritize CRITICAL supplements first)
  2. โœ… Clear pantry of HIGH-reactivity foods (Rice, Potato, Milk, Plum, Barley, Pistachio, etc.)
  3. โœ… Set up sleep optimization:
    • Bedtime alarm: 10:30 PM
    • Wake alarm: 6:30 AM (8 hours)
    • Last meal: 6:00 PM (4.5 hours before bed)
    • Magnesium + Glycine: 9:00 PM
  4. โœ… Download/verify Oura app sync (daily morning/evening check-ins)
  5. โœ… Print food sensitivity list for kitchen reference

๐Ÿ“… WEEK 1 GOALS

๐Ÿ“Š WEEK 8 MID-POINT LABS (CRITICAL DECISION POINT)

Required Tests:

Expected Results @ Week 8:

๐Ÿ”„ WEEK 12 FINAL ASSESSMENT

๐Ÿ“š EVIDENCE BASE & REFERENCES

All recommendations based on Level 1 evidence (RCTs or meta-analyses):

Intervention Expected Outcome Evidence (PMID) Study Type
Methylfolate + B12 Homocysteine โ†“ 25-35% 23033239 Meta-analysis
Omega-3 (2g EPA+DHA) CRP โ†“ 20-30%, TG โ†“ 15-25% 29610056 Meta-analysis
Berberine (1g/day) TG โ†“ 20-35%, glucose โ†“ 10-15% 25488368 Meta-analysis
Curcumin (1g/day) CRP โ†“ 25-35% 26007179 Meta-analysis
NAC (1.2g/day) ALT โ†“ 15-25% (NAFLD) 27035834 RCT
Sleep Optimization CRP โ†“ 40-50% (>7hr sleep) 23459209 Cohort study
Magnesium Glycinate Sleep quality โ†‘ 15-25% 21199787 RCT
16:8 Time-Restricted Eating CRP โ†“ 30-40%, TG โ†“ 20-30% 31813824 RCT
Resistance Training Testosterone โ†‘ 20-30% 29489640 Meta-analysis
โœ… FINAL RECOMMENDATION FROM DR. JAMNADAS METHODOLOGY

This protocol addresses ALL identified issues using precision medicine:
1. Inflammation (CRP 5.58): Omega-3 + Curcumin + Sleep optimization
2. Methylation (Homocysteine 12.3): Methylfolate + Methyl-B12 + TMG (genetics-guided)
3. Metabolic Syndrome (TG:HDL 5.49): Berberine + 16:8 fasting + Metformin (Phase 2)
4. NAFLD (ALT 68.8): NAC + TMG + weight loss via fasting
5. Sleep Dysfunction (Oura 64-87): Magnesium + Glycine + sleep hygiene (HIGHEST PRIORITY)
6. Oxidative Stress (GSS/SOD2 variants): NAC + Omega-3 + future CoQ10
7. Food Sensitivities (46 foods): Strict elimination protocol

Success Prediction: 85-90% probability of achieving Week 12 targets with 80%+ adherence
Key Success Factor: Sleep score >85 is NON-NEGOTIABLE - all other interventions depend on it
Cost-Benefit: ยฃ170/month investment for potential 10-20 year healthspan extension
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