Konrad Wright
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The Mr. Happy Stack

Uridine, fish oil and choline

I’m not a doctor and none of this is advice: talk to yours before you take any of it, especially if you take other medication.

The stack

A friend's stack, emailed to me in November 2020. He'd taken it since 2014–15, when he found it on r/nootropics while looking for help with depression.

  1. Uridine monophosphate

    The core of the stack. A building block the body uses for RNA and cell membranes.

    Per capsule
    350 mg
    Range a day
    1–4 (350–1,400 mg)
    His usual
    2 (700 mg)

  2. High EPA/DHA fish oil

    Omega-3 fats used in brain cell membranes. He's picky about quality: buy fresh, high EPA/DHA oil.

    Per softgel
    1,400 mg of oil
    Range a day
    2–6 (2,800–8,400 mg)
    His usual
    5 (7,000 mg)

  3. Choline (CDP choline or Alpha-GPC)

    The third membrane ingredient. Citicoline (CDP choline) is what he takes; Alpha-GPC is the other common form.

    Per capsule
    300 mg
    Range a day
    1–4 (300–1,200 mg)
    His usual
    1 (300 mg)
  • Timing All three at once, an hour or two before a workout. He likes it with black coffee, and 75–90% dark chocolate after.
  • Ratio About 1 choline for every 2 uridine, and more fish oil as the uridine goes up.

His numbers, in the capsule sizes he bought. Fish oil is listed by the oil, not the EPA and DHA inside it, which varies by brand: check your label. Not a recommendation.

The claims

  • No evidence foundIt was made to repair the brain damage methamphetamine causes.

    We couldn't find a study doing this. The closest human work is a small, open-label trial of uridine (500 mg twice a day for 6 weeks) in depressed teenagers with bipolar disorder. [6]

  • Animals onlyUridine and fish oil work better together.

    In rats, uridine worked immediately against depression-like behavior and omega-3s slowly; together the benefit came faster. [1]

  • MixedThe three together build new brain connections.

    In gerbils, uridine plus DHA (with choline) raised synaptic proteins by 38–41% in 4 weeks. In people, a drink built on the same idea missed its main goal in a 2-year trial of 311 people with early Alzheimer's, with some positive secondary results. [2] [3]

  • Some supportFish oil lifts mood.

    Modestly, and it depends on the oil: across 26 trials, formulas that were at least 60% EPA, at 1 g a day of EPA or less, helped depression. DHA-heavy oil didn't. [4]

  • MixedCholine sharpens focus and memory.

    500 mg a day of citicoline improved episodic memory over 12 weeks in 99 older adults with age-related memory complaints, in one trial funded by the maker. [5]

  • No evidence foundThe effects build, never wear off and stay after you stop.

    We found no research on tolerance or lasting effects for this combination.

  • No evidence foundIt makes coffee and other stimulants hit harder.

    We found no research on this.

Safety

  • Uridine is thinly studiedDenmark's National Food Institute couldn't rule out a health risk at 300 mg a day, not because of known harm but because there are almost no safety studies. Alzheimer's trials gave 625 mg a day for 24 weeks without obvious toxicity. His usual 2 capsules are 700 mg. [7]
  • Fish oil and heart rhythmAcross 7 trials and 81,210 people, omega-3 supplements raised the risk of atrial fibrillation by 12% at 1 g a day or less and by 49% above 1 g. The FDA and EFSA consider up to 5 g a day of EPA plus DHA safe. [8] [9]
  • Fish oil and blood thinnersFish oil can nudge clotting times up with warfarin. Doses of 3–6 g a day didn't change anticoagulation in studies, but anyone on a blood thinner should have their INR checked. [9]
  • Alpha-GPC and strokeIn a 10-year Korean cohort of over 12 million adults aged 50+, people prescribed Alpha-GPC had about 43% more strokes. It's an association, not proof, but it's a reason to prefer citicoline. [10]
  • The brain cancer worryHe mentioned a possible risk for people with a family history of brain cancer. We found no human evidence either way.

References

Meta-analysis04 / 10

Efficacy of omega-3 PUFAs in depression

Liao et al. · Translational Psychiatry · 2019

26 trials, 2,160 people. EPA-major formulas (≥60% EPA) at ≤1 g/day of EPA helped; DHA-major didn't.