Metabolism
NAD+ and NADH
Nicotinamide adenine dinucleotide, and its reduced form are coenzymes for many oxidation and reduction reactions in cells.
NAD+ and NADH form a critical redox couple whose ratio, rather than absolute quantity, defines cellular health. Ray Peat argued that in normal oxidative metabolism, the cell maintains an extreme preponderance of the oxidized form, with NAD+ outnumbering NADH by three to five hundred, or even seven hundred, to one. This highly oxidized state reflects a rapidly oxidising environment where electrons from fuel substrates like sugar are efficiently streamed through NAD+ to the mitochondrion and finally to oxygen. Stressors that interfere with oxygen availability or deplete the total pool of these nucleotides cause a failure of this balance, shifting the cell toward a reduced, NADH-dominant state that is characteristic of sickness and aging.
The shift toward a low NAD+/NADH ratio is both a consequence and a driver of metabolic dysfunction. Peat identified that a buildup of NADH acts as a signal to turn off pyruvate dehydrogenase (PDH), the enzyme complex that links glycolysis to the Krebs cycle. This blockade forces the cell to reduce pyruvate to lactate as an emergency oxidant to regenerate NAD+, a process that reinforces the reductive stress and leads to a destructive, primitivizing metabolic direction. In the absence of sufficient oxygen to accept electrons, Peat noted that the cell activates an intrinsic alternative: the synthesis of fats, driven by estrogen and other stressors, to consume the excess NADH. Georgi Dinkov has written that this is why using pyruvate to oxidize NADH back to NAD is "really bad," as it essentially mimics a cancer metabolism.
A major point of contention in the scientific community, according to Peat, is the interpretation of this ratio. He stated that many researchers, including prominent ketosis advocate Richard Veech, hold a "very confused attitude," believing that a higher proportion of the reduced form, NADH, is optimal. Peat fundamentally disagreed, aligning his view with the bioelectronic perspective of Gilbert Ling, where the cell's healthy state is defined by a scarcity of electrons. He explained that carbon dioxide functions as a cardinal adsorbent that pulls electrons out of the system, acidifies proteins, and shifts the entire electronic state of the cell toward the oxidized NAD+ side. This concept is supported by the discovery of trans-plasma membrane oxidases, which demonstrate that cells can remove electrons and oxidize NADH to NAD+ right at the cell surface, without mitochondrial involvement.
The total pool of NAD+ and NADH is vulnerable to catastrophic depletion, particularly during DNA damage. Peat described how the repair of DNA strand breaks by PARP enzymes consumes large amounts of the NAD+/NADH pool to build repair chains, and excessive damage can drain this pool so severely that it cripples cellular energy production. He identified niacinamide as a very safe PARP inhibitor that can prevent this wasteful depletion, giving the cell a chance to rest or proceed to apoptosis. Dinkov has extended this, noting that niacinamide's primary role in restoring the NAD+/NADH ratio is not simply as a precursor, but through its ability to lower lipolysis, which allows for more glucose metabolism and shifts the ratio back in favor of NAD+. This contrasts with popular but misguided approaches like NAD+ IV drips or the use of NADH pills, which Dinkov criticizes as an expensive and less safe alternative to simple precursors like niacinamide.