4.16 THIS IS HOW WE DO IT: Can we combat the fatigue and reduced cognitive functioning of jet lag with NADH pills?

Often, scientific thinking is applied to questions about the natural world with the sole purpose of better understanding organisms and how they function. In other cases, research questions are formulated and investigated with the intention of applying the knowledge gained to address specific problems.

In many cases, the transition to applied science is a logical and natural outgrowth of basic research. Consider the question of treating the serious effects of jet lag.

Jet lag occurs when a person travels across several time zones and there is a mismatch between her body clock and the time of day or night at her destination. It is accompanied by a constellation of symptoms, including fatigue, gastrointestinal distress, memory loss, and reductions in cognitive performance.

Jet lag affects a large number of travelers including pilots and other air crew. It can have serious consequences because it hinders decision-making abilities, effective communication, and memory.

Researchers suspected that interventions targeting cellular respiration—with an eye toward increasing the rate at which cells generate ATP—might decrease the fatigue experienced in jet lag. In particular, they have focused on the high-energy electron carrier NADH. As we saw in the previous section, during cellular respiration energy is captured in the high-energy electron carriers NADH and FADH₂.

If levels of NADH could be increased simply by taking the molecule in pill form, this might, given the central role of NADH as a source of potential energy, lead to increased production of usable energy through the electron transport chain. And so this hypothesis gave rise to a testable prediction: “Supplementing NADH should counteract some of the effects of jet lag, including reduced cognitive functioning and fatigue.”

The experimental setup. The researchers used a randomized, controlled, double-blind experimental design. The participants were 36 volunteers, 35-55 years old, with at least 14 years of formal education and normal sleep schedules. During the study, the participants did not consume any caffeine, alcohol, or any medications known to affect nervous system functioning.

The volunteers were randomly assigned to one of two groups, placebo or NADH, and took a battery of tests to establish their baseline performance. They then took an overnight “red-eye” flight across four time zones, from California to Maryland. They arrived at 6 A.M., were given breakfast, and were then administered a pill containing either NADH or a placebo. At 9:30 A.M. and again at 12:30 P.M., they were given the same battery of tests.

Overall, the participants receiving NADH performed significantly better on four tests of cognitive functioning and reported less sleepiness. The results from the specific tests suggest that the improvements in cognitive functioning experienced by the NADH-taking subjects have real-world relevance.

1. Vigilance. Participants watched a computer monitor and responded each time they saw a particular symbol. They were scored on the number of errors they made, particularly “errors of omission” indicating lapses of attention. Here are the results for the two groups:

2. Working memory. The participants were required to remember numbers and perform mental operations on them.

3. Multi-tasking. Participants were required to shift between two different tasks that involved marking numbers on a spreadsheet.

4. Visual perception. Participants viewed a 4 × 4 checkerboard pattern and, on the screen that followed, had to identify the matching pattern.

5. Sleepiness. Participants self-reported their sleepiness on a 7-point scale.

The results reported in this well-designed study were clear and definitive. The placebo-receiving jet-lagged volunteers were more likely to make errors related to not paying attention, had greater difficulty with memory and concentration, and were less effective at multi-tasking. The researchers’ conclusion, supported by the evidence, was that “NADH appears to be a suitable short-term countermeasure for the effects of jet lag on cognition and sleepiness.”

While the results do support the researchers’ hypothesis, it still may be premature to consider the issue completely resolved. As they pointed out, the optimal doses of NADH still need to be investigated. Additionally, they only examined the subjects’ response to NADH directly following the red-eye flight. It is not clear what the duration of the effect of NADH might be on cognition and sleepiness.

It is wise, also, to be aware of any biases—even unconscious biases—that might influence researchers. In this study, for example, the researchers reported that “Menuco Corporation funded the study.” A quick search reveals that Menuco Corporation was founded by one of the study’s authors and is a for-profit company that markets and sells NADH supplements. The company and author hold the patent for the manufacturing process of the NADH supplement used in the study.

These facts do not invalidate the results, however. The study was carefully controlled and well designed. And most important, the researchers described their methods in such detail that the research can be replicated. Given the small number of subjects in their study, as well as the increasing relevance of jet lag in today’s world, replication of these findings would be an important factor in increasing our confidence in the generalizability of the conclusions.