MTHFR is a real gene in the folate pathway, but it often gets treated like it explains everything. This episode keeps the scale right. You’ll learn what the enzyme does, why homocysteine became a popular lab marker, and how to separate association evidence from intervention evidence so you don’t get misled by a number moving without outcomes changing. You’ll also get a simple decision model you can use without spiraling.

You’ll learn:

• What MTHFR actually does inside folate metabolism

• Why folate was historically studied in medicine

• How homocysteine became a biomarker

• Why association studies and randomized trials tell different stories

• What DNA methylation actually means

• Why this is a pathway discussion, not a personality explanation

This episode separates evidence types carefully and keeps claims proportional to data.

Timestamps

0:00 Primary intro

1:05 Why MTHFR gets inflated in conversation

2:00 Folate history and why it mattered in medicine

3:00 One carbon metabolism explained clearly

4:15 What MTHFR enzyme actually does

5:20 B12 as cofactor and why this is a pathway, not a solo gene

6:10 Homocysteine as a biomarker and what association means

7:20 Randomized trials lowering homocysteine and outcome nuance

8:40 DNA methylation defined properly

9:50 What MTHFR does not control

10:40 Mendelian randomization and causality

11:30 Micro protocol and bridge to Part 2

Key Terms

Folate: A B vitamin required for DNA synthesis and red blood cell formation. Named from the Latin “folium,” meaning leaf.

One carbon metabolism: A network of reactions that transfer single carbon units for DNA synthesis and methylation reactions.

MTHFR: Methylenetetrahydrofolate reductase, an enzyme that converts one form of folate into another needed for homocysteine recycling.

Enzyme: A protein that speeds up a chemical reaction.

Homocysteine: An intermediate amino acid in methionine metabolism that can accumulate if recycling is impaired.

Methionine: An essential amino acid involved in protein synthesis and methyl group donation.

Vitamin B12: A vitamin that acts as a cofactor for methionine synthase in homocysteine conversion.

Cofactor: A helper molecule required for an enzyme to function.

Biomarker: A measurable biological indicator, often assessed through blood testing.

Association: When two variables move together statistically; does not prove cause.

Randomized controlled trial: A study design that assigns participants by chance to test cause and effect.

DNA methylation: The addition of methyl groups to DNA that can influence gene expression levels.

Gene expression: The process by which a gene is used to produce a protein.

Mendelian randomization: A genetics based method using variants as natural experiments to estimate causality.

Keywords

MTHFR, folate cycle, homocysteine, methylation, one carbon metabolism, B12, C677T, gene expression, cardiovascular risk, Mendelian randomization

References

NIH Office of Dietary Supplements. Folate Fact Sheet for Health Professionals.

NIH Office of Dietary Supplements. Vitamin B12 Fact Sheet for Health Professionals.

HOPE 2 Investigators. NEJM. 2006.

NORVIT Trial Investigators. NEJM. 2006.

Clarke R et al. Homocysteine and vascular disease. JAMA. 2002.

Recent Mendelian randomization analyses on homocysteine and cardiovascular outcomes, 2018–2023.

Episode 7 Part 2 continues directly from Part 1 and turns MTHFR from a confusing gene label into practical decisions you can use. We walk through homocysteine as a pathway signal, why observational associations are not the same thing as cause, and what randomized trials taught us about lowering homocysteine versus improving real world outcomes. You’ll also learn what common lab terms mean in plain language, including serum B12, serum folate, and RBC folate, and why each test gives a different kind of picture. From there we translate micrograms and kilograms into normal food and bodyweight anchors, then bring in the brain layer with neurotransmitters, methylation, and gene expression kept in proportion. ADHD is addressed as an applied example without making it the headline. We close with a detailed, repeatable protocol focused on labs in context, folate and B12 consistency, protein targets, iron and omega 3 foundations, and sleep stability.

Timestamps

0:00 Primary intro and safety disclaimer

0:37 Bridge from Part 1 and what Part 2 solves

1:45 Homocysteine, association versus causation, and why trials changed interpretation

3:19 Lab terms decoded, serum B12, serum folate, RBC folate

4:53 Units made human, micrograms, folate targets, food examples

5:10 B12 planning, fortified foods, consistency

6:12 Protein targets, kilograms, 1.6 g per kg, meal anchors

8:23 Brain layer, neurotransmitters, methylation, gene expression

8:41 ADHD as an applied example, polygenic meaning many genes

10:30 Ferritin and iron, what it means, food sources, absorption tip

12:22 Omega 3, EPA and DHA, evidence summary, food sources and ranges

13:42 Sleep and stress, how instability amplifies symptoms

14:32 Protocol begins, labs plus food and training anchors

15:30 Two week stability challenge

15:36 Close and final line

17:29 End

Key Terms

Microgram: One millionth of a gram, used for vitamins and minerals because they work in small amounts.

Kilogram: A unit of bodyweight equal to about 2.2 pounds.

Protein adequacy: Consuming enough protein to support tissue repair and training adaptation, often around 1.6 g per kg per day for resistance training contexts.

Polygenic: Influenced by many genes that each contribute small effects.

Ferritin: A blood marker used to estimate iron storage.

Omega 3: A family of fats, including EPA and DHA, studied for brain and behavioral outcomes.

EPA: Eicosapentaenoic acid, an omega 3 fat studied in inflammation and brain related outcomes.

DHA: Docosahexaenoic acid, an omega 3 fat important for neural tissue structure and function.

Keywords

MTHFR,micrograms, kilograms, protein, gene expression, polygenic, ferritin, iron, omega 3, EPA, DHA,

References

Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease. New England Journal of Medicine. 2006.

Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction. New England Journal of Medicine. 2006.

Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta analysis and meta regression of the effect of protein supplementation on resistance training induced gains. British Journal of Sports Medicine. 2018.

NIH Office of Dietary Supplements. Folate Fact Sheet for Health Professionals.

NIH Office of Dietary Supplements. Vitamin B12 Fact Sheet for Health Professionals.

Tseng PT, et al. Peripheral iron levels in children with ADHD. Scientific Reports. 2018.

Liu TH, et al. Omega 3 Polyunsaturated Fatty Acids for Core Symptoms of ADHD. Journal of Clinical Psychiatry. 2023.

The Unlocked Podcast is educational content, not medical advice. For personal medical decisions, consult a qualified professional.

A short guided practice to downshift, recover, and ground the nervous system.

This episode is a guided nervous system reset designed to help you downshift from stress, stimulation, or mental overload.

You don’t need a yoga studio, special equipment, or prior experience. This practice can be done seated or lying down, at home, after work, after training, or before sleep.

The breathing and awareness used here are intended to support recovery by gently shifting the nervous system out of a high-alert state and toward a calmer, more regulated one. Over time, practices like this can support better sleep, digestion, emotional regulation, and overall recovery.

This session is not about forcing relaxation or clearing the mind. It’s about giving the body enough space to settle naturally.

You can return to this reset anytime you feel overstimulated, scattered, or in need of grounding.

What You Need

A quiet space where you can sit or lie down comfortably.

A chair, mat, couch, or bed all work.

Optional: a light blanket if the room is cool.

After the Practice

Try to keep the transition gentle.

Hydration is helpful.

If you eat afterward, warm, grounding foods are often more settling than highly stimulating options.

Your biology listens. Live like it.