thescientist | For three consecutive winters, starting in
2011, researchers at the University of Birmingham asked healthy men and
women over the age of 65 to come in to clinics across the western
Midlands in the U.K. for a seasonal influenza vaccination at specific
times of day—either between 9 and 11 a.m., or between 3 and 5 p.m. Blood
drawn a month later revealed that participants, who totaled nearly 300
over the three years, had higher levels of anti-flu antibodies if they’d
received their vaccinations in the morning.1 The results suggested that daily rhythms of people’s bodies tweaked the vaccine’s effectiveness. Lead author Anna Phillips Whittaker
had suspected as much, after observing similar trends in her studies on
behavioral factors such as exercise that affect vaccination responses,
and in the wake of a growing body of literature suggesting that a little
timing can go a long way when it comes to health.
Many hormones and immune signals are produced rhythmically in 24-hour
cycles. Cortisol, for example, which is known to suppress inflammation
and regulate certain T cell–mediated immune responses, peaks early in
the morning and ebbs as the day progresses. Other facets of the immune
system undergo similar cycles that could underlie the differences in
antibody responses Phillips observed among people receiving the flu
vaccine. Much more work is required to nail down the immune mechanisms
responsible for such variation and exploit them appropriately, she says.
But timing flu vaccine delivery would be straightforward to implement.
“It’s such a simple, low-risk intervention that’s free to do, and could
have massive implications for vulnerable populations.”
Across diseases, from cancer and cardiac ailments to allergies and
arthritis, epidemiological data and clinical trials are revealing that
timing medications to the body’s internal clock could improve their
effectiveness and reduce side effects. Although this concept, known as
chronotherapy, has existed for at least 60 years, it has received little
attention from physicians. But as biologists continue to unveil the
molecular intricacies of cellular rhythms, they are beginning to realize
just how pervasive the circadian clock’s influence is. In a 2014 study
of gene expression in mice, for example, researchers found periodic
expression in conserved mammalian genes targeted by 56 of the top 100
best-selling drugs in the U.S., including aripiprazole (Abilify, an
antipsychotic), esomeprazole (Nexium, for heartburn), and duloxetine
(Cymbalta, for depression), even though most are not currently
prescribed with suggested dosing times.2
But chronotherapy is gaining clinical traction, says University of
Pennsylvania chronobiologist John Hogenesch, senior author on the 2014
study. “Now we have the groundwork to precisely understand a person’s
clock and leverage that information for better health,” he says.
“Because of the molecular work, we’ve opened new doors here. This [idea]
is not coming from left field anymore.”
Even so, researchers and clinicians working on chronotherapy still face
skepticism, and implementing a new drug-delivery protocol or gaining
regulatory approval from the US Food and Drug Administration (FDA) for
time-of-day indications remains challenging. Thus, while the biomedical
research community is starting to take notice of the body’s internal
rhythms, timed therapies are still the exception to the rule.
1 comments:
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