Genetic Polymorphisms: Tailor Your Scorch Protocol to Your DNA

Fasting, especially dry fasting in the Scorch Protocol, supercharges metabolism but can backfire if your genes impair T3 (active thyroid hormone) signaling. Understanding your genetic variants allows you to customize the protocol for maximum safety and effectiveness.

Why Genetics Matter for Fasting

The Core Issue Certain genetic variants reduce T3 conversion by 20-40%, amplifying fasting's natural "low T3 slowdown" into fatigue, weight rebound, and chronic illness flares.

The Opportunity These SNPs explain 5-15% of thyroid variance. Genotype-aware fasting cuts risks by 50% while unlocking deeper autophagy.

Core Culprit: DIO2 Thr92Ala (rs225014)

What it does: Swaps threonine for alanine at codon 92, slashing local T3 production in muscle, brain, and brown fat. Thr/Ala or Ala/Ala carriers (12-50% prevalence) run 10-20% lower RMR, with higher BMI and glucose.

Fasting Risk for DIO2 Carriers

The Danger Dry fasts drop T3 by 20-50% normally. Carriers hit 40%+ nadir, risking muscle loss, insulin spikes, and post-fast yo-yo weight.

The Mechanism It's "local hypothyroidism" in disguise—mimics stress states like COVID, fueling neurodegeneration and metabolic stall.

Actionable Steps for DIO2 Carriers

Test Your DNA: Upload Ancestry.com raw data to Promethease; flag if Thr/Ala or Ala/Ala.
Modify Fasting: Start with wet fasts (12-16h); limit dry fasts to <24h initially.
Track Biomarkers: Monitor FT3/TSH pre/post-fast to catch crashes early.
Selenium Support: Add 200mcg/day to boost deiodinase activity by 20%.
Consider T3 Therapy: If carrier with stubborn hypothyroid symptoms, consult for LT3 (liothyronine).

The Keto-DIO2 Metabolic Trap

Keto research often highlights metabolic flexibility and thyroid adaptability during long-term ketosis. For most people, T3 reductions on keto reflect efficient energy shifts, not dysfunction. But this overlooks a critical genetic vulnerability.

Why DIO2 Carriers Struggle on Keto

The DIO2 Thr92Ala polymorphism (rs225014) is common, affecting 12-56% of populations. It impairs peripheral T4-to-T3 conversion and amplifies T3 suppression in low-carb states.

The Cascade for Carriers:

Blunted Intracellular T3: Hampers mitochondrial ATP production, reducing cellular energy.
Insulin Resistance: Low T3 worsens glucose metabolism and fat storage.
Elevated Cortisol: Chronic stress hormone activation from metabolic slowdown.
Inefficient Fat Oxidation: Despite being in ketosis, fat burning becomes sluggish.
Persistent Symptoms: Fatigue, cold intolerance, brain fog that resist simple carb reintroduction.

The Low-Energy Trap: This suppression throttles cellular respiration and CO2 output. What should be a "thrifty" adaptation becomes a hard-to-reverse metabolic prison.

The Solution: Genotyping for DIO2 variants is essential. For carriers, prioritize pro-thyroid, carb-inclusive strategies over blanket keto endorsements. This ensures truly optimized metabolism instead of a metabolic dead end.

Ethnic Prevalence: Who's Most at Risk?

The DIO2 Thr92Ala (Ala allele) variant shows significant ethnic variation. European populations are particularly susceptible, with some of the highest carrier rates globally.

Ancestry	Ala Allele Frequency	Thr/Ala Carriers	Ala/Ala (Homozygous)
Finnish	37.4%	47.1%	13.9%
Northern European	34.2%	46.3%	10.4%
Ashkenazi Jewish	33.1%	45.6%	9.7%
European (non-Finnish)	31.9%	44.8%	8.8%
Latino/Admixed American	25.4%	38.5%	5.8%
African/African American	16.2%	26.8%	2.0%
East Asian	13.7%	22.2%	1.3%

Key Insight: If you are of European descent, there's a ~45-60% chance you carry at least one Ala allele, making genotype testing especially critical before aggressive dry fasting protocols.

Companion SNPs: Amplified T3 Vulnerability

These variants stack with DIO2 for 2-3x fasting intolerance. Prioritize polygenic scores (sum risks).

SNP/Gene	Risk Allele	Fasting Impact
DIO1 (rs2235544)	A allele (AC/AA genotypes)	Reduces liver T3 conversion 15-30%, worsening gluconeogenesis crash and rT3 buildup during dry fasts.
MCT10 (rs17606253)	G allele (AG/GG genotypes)	Impairs T3 cell uptake by 20%, starving tissues. Dehydration amplifies "T3 blockade," spiking inflammation/gut issues.
TSHR (rs12050029)	T allele (CT/TT genotypes)	Raises TSH set-point 0.1-0.3 mU/L, delaying HPT axis recovery. Fast stress suppresses TSH harder, mimicking central hypothyroidism.
FTO (rs9939609)	A allele (TA/AA genotypes)	Boosts ghrelin 20-30%, driving post-fast binges. Low T3 + A allele = leptin resistance, locking in fat storage/insulin spikes.

Need Personalized Guidance?

Genetic interpretation and protocol customization can be complex. If you need 1-on-1 support for DNA-based fasting optimization, consider booking a session with Yannick Wolfe.

What you get: Personalized SNP analysis, custom fasting schedules, and biomarker tracking tailored to your genetic profile.

Guarantee: Full refunds offered for anyone that does not achieve their goals with 1-on-1 guidance.

Visit DryFastingClub.com

Genetic Profile & Protocol Notes

Log your SNP results and how you modified the protocol based on your genetics.