The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 7 • December 2016

(continuation of the series by Sandy Shaw)

Sometimes old papers contain important information that has become forgotten or ignored over time. These “oldie but goodies” are sometimes worth spending some time with—they can act like a time machine for recalling past discoveries that may point the way to new thinking about an old subject.

So it goes with a paper from 1981 (Klein, 1981) that investigated the loss of nicotinamide enzymes (including NAD+) in the ischemic-infarcted hearts of dogs. What these researchers found was that loss of NAD+, MADH, and NADPH, nicotinamide adenine dinucleotides, “may be responsible for the transition from reversibly ischemic to irreversibly infarcted cell damage.”

As the authors explain, “Ischemic myocardium undergoes a sequence of biochemical changes until it becomes irreversibly damaged.” What this means is that initial damage may be reversible if conditions are right and prevent irreversible damage which leaves the heart permanently weakened. At that time (1981), the biochemical mechanism that led to this permanent damage had not been worked out. The authors thought that the loss of NAD+ might account for this.

Under the conditions of their study, the researchers found a loss of total NAD+ of about 60-70% when they diagnosed irreversible cell injury by electron microscopy. Total NAD, the sum of NAD+ and NADH, “started to decrease significantly in the ischemic subendocardium 1 hour after onset of ischemia” and “... started ... to become significant after two hours of ischemia.” The researchers summed up their results: “We conclude from our data that the loss of the nicotinamide coenzymes is crucial for the irreversibly ischemic injury.” They note that in rat hearts a loss of 60% of NAD could theoretically mean that either the mitochondria or the cytoplasm is totally without NAD, with the result being a severe decrease in the ability to produce ATP.


  • Klein et al. Loss of canine myocardial nicotinamide adenine dinucleotides determines the transition from reversible to irreversible ischemic damage of myocardial cells. Basic Res Cardiol. 76:612-21 (1981).

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