Plasmalogens are one of the oldest, most fundamental molecules inside the human body, yet almost no one talks about them. If you imagine the cell as a city, plasmalogens are the shock-absorbing pavement, the insulation around every electrical wire, and the structural glue that determines how well the buildings hold up under stress. They make up a significant portion of the membranes around our cells, especially in the brain, heart, immune system, and mitochondria. They’re not used as fuel, they’re not signaling hormones, and they’re not vitamins they are architectural lipids, meaning their entire purpose is to create the “physical environment” inside which every biochemical reaction occurs. When this architecture is strong, cells communicate clearly, mitochondria keep up with energy demands, neurons fire smoothly, and tissues age more slowly. When plasmalogens decline as they do with aging, chronic inflammation, metabolic disease, and overtraining the whole system becomes more fragile. Surfaces become leaky. Signals get distorted. Energy becomes harder to make. And we see it clinically as brain fog, slower recovery, impaired metabolism, chronic fatigue, mood instability, and higher disease risk. To understand plasmalogens, you first need to understand the membrane. The membrane is the barrier between chaos and order. It keeps the inside of the cell different from the outside. But it’s not a hardened shell; it’s a flexible, dynamic, constantly-moving layer of phospholipids, cholesterol, proteins, and microdomains. Think of it like a high-tech trampoline. Every receptor sits in this trampoline. Every transporter is anchored to it. Every signal, from insulin binding to the NMDA receptor firing, depends on how stable and well-organized that trampoline is. Plasmalogens sit inside this membrane like reinforced beams with a special vinyl-ether bond. This bond is unique: it actually absorbs oxidative damage like a sacrificial shield. Instead of letting free radicals tear up the membrane, plasmalogens get hit first and protect the surrounding structure. This is why they are most concentrated in tissues with the highest oxidative stress—neurons, muscle, heart, immune cells, and mitochondria. When plasmalogens are low, cell membranes become thinner, more fragile, and more prone to dysfunction. Receptors do not cluster properly, inflammation becomes easier to trigger, and mitochondria lose their tight coupling between electron flow and ATP production. In other words, membranes lose intelligence.

Methylene blue is one of the most unusual therapeutic molecules in medicine because it behaves like a living sensor inside the body. It changes color depending on its electron state, donates and accepts electrons depending on mitochondrial demand, bypasses damaged respiratory complexes, and flows directly into the bloodstream, nervous system, and organs as a redox-active dye. While people know it turns urine blue, they rarely understand why that color appears, why the duration changes, and how those changes can reveal meaningful information about mitochondrial efficiency, liver and kidney function, and global redox tone. The truth is that the color shift is not just a cosmetic effect; it is a visible expression of the electron flow inside your cells. The speed at which urine returns to its normal yellow color becomes a rough, experiential marker of how well your body’s redox machinery is cycling. To understand this, the first step is recognizing that methylene blue exists in two major states: its oxidized form (bright blue) and its reduced form, leucomethylene blue, which is colorless. These two forms constantly convert into one another based on the availability of electrons. When methylene blue accepts electrons, it becomes colorless. When it donates electrons, it becomes blue again. This redox cycling is what makes methylene blue so therapeutically valuable it acts like a smart shuttle that smooths out problems in the electron transport chain, especially when complex I or III are underperforming. When mitochondria are stressed, over-reduced, under-fueled, oxidatively burdened, or deprived of NAD+, methylene blue helps buffer the system by accepting excess electrons or donating needed electrons. It reduces oxidative stress, stabilizes the flow of energy, and helps maintain membrane potential. But because it is also a dye, these internal dynamics show up externally, especially in urine. The moment methylene blue enters the bloodstream, the body begins metabolizing it in the liver, reducing it, cycling it, moving it into tissues, and eventually clearing it through the kidneys. The exact hue you see in the toilet depends on two things: how much of the molecule remains in its oxidized blue form versus its reduced colorless form, and how concentrated your urine is. Dark, heavily oxidized methylene blue produces a vivid blue-green color. When most of the MB is reduced and colorless, urine appears normal or lightly tinted. This is why two people taking the same dose can see dramatically different colors. The real insight emerges when you track how long the color lasts.

Has anyone here used ARA290?

SLU-PP-332 is one of the most misunderstood compounds in the entire performance and longevity space, and nowhere is that misunderstanding more obvious than in the topic of water retention. People experience it, panic, and immediately assume “estrogen,” “bad purity,” “toxicity,” or “my body isn’t responding to SLU correctly.” But when you break down what’s actually happening at the cellular level, the explanation is far more interesting, far more predictable, and far more fixable than people realize. Water retention with SLU isn’t random. It’s not a flaw in the compound. It’s a message from your system saying, “Your signaling is mismatched.” In this article, we’re going to break down what that means, why it happens, how SLU interacts with AMPK, ERRα, and renal sodium handling, and what the body is actually trying to do. By the end, beginners will understand the big picture clearly, and advanced clinicians and coaches will be able to teach it to others. To understand SLU and water retention, you first need to understand what SLU is actually doing. SLU is not a fat burner. It is not a stimulant. It is not a thermogenic drug. SLU is a pan-ERR agonist meaning it activates estrogen-related receptors alpha, beta, and gamma. These receptors live inside the nucleus and act like metabolic switchboards. They determine which genes get turned on to burn fat, use oxygen, increase mitochondrial respiration, create new mitochondria, and shift fuel preference. ERRα in particular is a master regulator of mitochondrial function. It influences everything from oxidative phosphorylation to uncoupling protein expression to metabolic adaptation under stress. When SLU binds to these receptors, it triggers the same gene programs normally activated by aerobic exercise: DDIT4, which senses metabolic stress and tells the cell to adapt, and SLC25A25, which helps shuttle fuel across the inner mitochondrial membrane so you can produce energy more efficiently. These genes are not surface-level actors. They’re deep in the machinery. They’re the electricians rewiring the power grid.

I’ve talked about this a few times before, but I know there are still plenty of questions around it so I wanted to take another shot at clearly explaining the reasoning behind my answer. The case against higher doses of SLU-PP-332 starts with first principles: this compound works as a signaling cue, not a substrate to be “pushed” toward saturation. In cell systems and animal models, SLU-PP-332 appears to activate the estrogen-related receptor (ERR) program with PGC-1α coactivation, shifting transcription toward fatty-acid oxidation, oxidative phosphorylation, and mitochondrial quality control. That kind of pathway is amplifier biology: a small receptor-level nudge fans out into many downstream genes and post-translational switches. In such networks, more ligand does not linearly equal more benefit; it often crosses into different biology entirely, including compensatory braking and desensitization. Think of it like tapping a conductor’s baton to set tempo versus throwing a bigger baton at the orchestra. The first coordinates; the second creates noise and reflexes you didn’t intend. A key downstream branch of the ERR/PGC-1α program is modulation of uncoupling proteins. Mild, context-appropriate uncoupling in UCP2 and UCP3 can lower electron pressure, trim reactive oxygen species, and improve metabolic flexibility under load. But pushing the axis hard increases the probability of off-site expression and activity in UCP4 and UCP5, which are enriched in neurons and glia. Excess uncoupling in those tissues risks local ATP shortfall where energy security is non-negotiable. In brain and autonomic circuits, too much leak across the inner mitochondrial membrane can force compensatory hypermetabolism to maintain voltage, distort calcium handling, and disturb neurotransmission timing. At the organism level, that looks like brain fog, dysautonomia, sleep fragmentation, and reduced stress tolerance exactly the systems you don’t want to pay for marginal fat-loss gains. Mechanistically, high-dose signaling also raises the odds of maladaptive redox and substrate partitioning. ERR/PGC-1α drive beta-oxidation and electron delivery to the respiratory chain. If you layer that on top of exercise, fasting, thyroid augmentation, or catecholamine tone, you can overshoot electron influx relative to complex-level throughput, increasing retrograde signaling and forcing the cell to dump potential as heat via uncoupling. At low dose this can be hormetic and helpful. At high dose, it can flatten the ATP/ADP ratio, trigger AMPK hard, suppress mTORC1 anabolics, and blunt hypertrophy. In muscle, that shifts toward more oxidative phenotype at the expense of contractile remodeling; in the heart, it risks energetics imbalance that the sinoatrial node and conduction system must buffer beat-to-beat.