Cofactors | Magnesium (TRPM6 rs3750425)

What this means

Carrying two copies of the effect allele is associated with modestly lower serum magnesium. This can reduce the efficiency of magnesium-dependent enzymes, including those in methylation such as COMT, and can lead to subtle disruptions in neurotransmitter breakdown, energy production, and homocysteine recycling.

Common signs to watch for

• Low or fluctuating energy
• Muscle tightness, spasms, or cramps
• Sleep disturbances or restless sleep
• Mood changes such as irritability or anxiety
• Persistent constipation or headaches in some people

Dietary recommendations

• Eat magnesium-rich leafy greens such as spinach, Swiss chard, and kale.
• Include nuts and seeds daily: almonds, cashews, pumpkin seeds, and chia.
• Choose legumes and beans: black beans, lentils, chickpeas.
• Prefer whole grains such as quinoa, brown rice, and oats.
• Enjoy small amounts of dark chocolate and avocados for extra magnesium.

Supplement and testing guidance

• Consider checking serum magnesium with your healthcare provider. Some clinicians also use red blood cell magnesium or ionized magnesium for a more detailed view.
• If tests show low magnesium or you have symptoms, discuss a low-dose supplement such as magnesium glycinate or magnesium citrate. Typical starting elemental magnesium ranges from 200 to 400 mg daily, individualized by your clinician.
• Take supplements with food to improve tolerance. Start at lower doses to assess GI tolerance and adjust under clinical supervision.

Lifestyle and medication considerations

• Limit excess alcohol and high caffeine intake which can increase magnesium loss.
• Stay well hydrated and maintain regular activity to support circulation and nutrient delivery.
• Manage stress with sleep hygiene, breathing exercises, or meditation to reduce magnesium depletion.
• Tell your healthcare provider about prescription or over the counter medications you take, as some can affect magnesium levels.

What this means

Having one copy of the effect allele is linked to a slightly lower blood magnesium level. The impact is usually modest but can subtly affect magnesium-dependent enzymes in methylation and neurotransmitter metabolism, especially if diet and lifestyle do not provide adequate magnesium.

Signs to monitor

• Mild low energy or fatigue
• Occasional muscle tightness or cramping
• Sleep or mood fluctuations
• Worsening symptoms with poor diet, high stress, or heavy alcohol use

Dietary recommendations

• Prioritize leafy greens, nuts, seeds, legumes, and whole grains.
• Add magnesium-rich snacks such as pumpkin seeds or nut butters.
• Balance calcium and vitamin D intake, as these nutrients interact with magnesium absorption.

Supplement and testing guidance

• Discuss a basic serum magnesium test with your healthcare provider if you have symptoms.
• If testing shows low or borderline magnesium, a clinician may suggest 200 to 400 mg elemental magnesium daily via glycinate or citrate. Adjust dose based on symptoms and tolerance.

Lifestyle tips

• Reduce behaviors that deplete magnesium, including excess alcohol and chronic stress.
• Improve sleep quality and include gentle movement such as walking or yoga.
• Review medications with your clinician to identify any that could lower magnesium.

What this means

Carrying two copies of the non-effect allele is associated with typical serum magnesium levels and normal magnesium transport. Enzymes that rely on magnesium are expected to function efficiently under usual dietary and lifestyle conditions.

Maintenance recommendations

• Continue a balanced diet that includes magnesium-rich foods: leafy greens, nuts, seeds, legumes, whole grains, and moderate dark chocolate.
• Consider a low-dose magnesium supplement such as magnesium glycinate 200 to 300 mg daily only if dietary intake is low, symptoms appear, or a clinician recommends it.
• Check serum magnesium if you experience new symptoms like muscle cramps, persistent fatigue, or sleep disturbances, or if you begin medications that affect magnesium.

Lifestyle tips

• Maintain regular physical activity and a consistent sleep schedule.
• Limit excess alcohol and very high caffeine intake.
• Manage stress with restorative practices and eat a varied nutrient-dense diet.