EFFECTS AND UNDERLYING MECHANISMS OF PHOTOBIOMODULATION (PBM) ON HEALTH AND WELL-BEING

Light plays key roles in human health and wellness. Despite of this, Western
societies spend about 85% of their waking hours indoors. In particular,
near-infrared (NIR 750- 1100 nm) light is completely absent indoors, while it
accounts for about 54% of the solar radiation reaching the earth. The
biological effect of NIR on human bodies has been termed photobiomodulation
(PBM) and it has roots in the medical environment. The FDA has approved PBM as
treatment for pain relief in cases of head and neck pain, arthritis and carpal
tunnel syndrome and more recently it became part of WALT/MASCC/ISOO guidelines.
New technologies have made it possible to safely introduce PBM outside the
medical framework, testing the possible beneficial effects on health and
well-being in a much larger population. Our previous study NL74857.04.20, has
revealed positive effects of PBM on mood, drowsiness, resting heart rate and
immune related outputs as well as some positive trends in reducing cortisol
just before sleep and shifting the dim light melatonin onset. This was the
first time that a double blind and placebo-controlled study shows positive
systemic effects of PBM in a generally healthy population (results are
currently under review for publication).

To follow up on the previous study on PBM effects on well-being by
prospectively assessing mood, drowsiness and depression as well as
energy/tiredness/tension/calmness, and sleep parameters, and on health by
prospectively assessing resting heart rate, cortisol at bed time, dim light
melatonin onset, TNF-alpha, IFN-gamma, and TFG-beta1, as well cytokines IL-1
and IL-6. We will further explore more mechanistic related questions by
assessing a) whether the eyes are needed for the observed PBM effect (eyes +
skin vs skin only), b) what are the effects of a different wavelength, or c) a
different pulse, as well as d) metabolomics quantification which will be used
to find the most likely pathways of action.

In a carefully conducted double-blind placebo-controlled field study, the
experiment will consist of a baseline measurement followed up by 2 weeks (5 PBM
sessions per week) of PBM intervention. A week before the baseline measurement,
participants will have to start wearing a Fitbit Versa 3, and will have to
continuously wear until the end of the study. In the afternoon of the baseline
day as well as in the afternoons after 5 and 10 PBM sessions (week 1 and week
2, respectively), participants will have to go to the lab for blood withdraw.
In the evening of the baseline day as well as in the evenings after 5 and 10
PBM sessions (week 1 and week 2, respectively), participants will have to
collect saliva samples as well as to complete questionnaires.

5 conditions will be tested: 2 PBM doses: 0 J.cm-2 (placebo), and 6.5 J.cm-2.
The PBM dose will either have a wavelength of 850 or 940 nm and a pulse of
either 15 Hz/8 ms or 100 Hz/1.2 ms, respectively (both resulting in a duty
cycle of 12%). Further, the PBM dose will also be tested with eyes blocked by
means of filtering glasses that provide almost clear visibility of 75% in
wavelenght used for vision, but filter wavelengths between 850-5200 nm. Dose
and timing will be programmed into the device, so that no user intervention
will be necessary.

The full protocol will be performed at the participants* home and/or workplace.
Participants will have to sit in front of the PBM module during 3 hours in the
morning (from 9:30 to 12:30) 5 days per week during 2 weeks. This is not really
a burden, since the device is a normal desk light, the only limitation is that
they need to stay at their desk during this time. During exposure to PBM they
should not cover the skin of their arms, hands and face nor wear any cream.
In addition, a week before the baseline measurement, participants will have to
start wearing a Fitbit Versa 3, and will have to continuously wear until the
end of the study. In the afternoon of the baseline day as well as in the
afternoons after 5 and 10 PBM sessions (week 1 and week 2, respectively),
participants will have to go to the lab for blood withdraw. In the evening of
the baseline day as well as in the evenings after 5 and 10 PBM sessions (week 1
and week 2, respectively), participants will have to collect saliva samples as
well as to complete questionnaires. All devices are used for ambulatory
recordings and do not inhibit the person*s behaviour. There are no risks
associated with participation. If PBM works, subjects may benefit from it.