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Preface

This risk-benefit analysis (RBA) is part of Forever Healthy's "Rejuvenation Now" initiative that seeks to continuously identify new therapies and systematically evaluate them on their risks, benefits, procedures and potential application.

Special thanks are extended to the whole Rejuvenation Now team at Forever Healthy for their friendly contributions.

Section 1: Overview 

Motivation

Low-level light therapy (LLLT) is the use of low incident levels of photon energy at a particular wavelength, targeting tissue to achieve a clinically useful local or systemic effect without the creation of heat (athermal) or damage (atraumatic) (Calderhead & Tanaka, 2017). LLLT has shown dramatic effects when used for wound healing, pain management, and various musculoskeletal conditions.

This review focuses on its potential use in skin rejuvenation. It has been shown that upon exposure to light, chromophores in the skin (mitochondrial cytochrome C, melanin, and protoporphyrins) absorb photons which lead to downstream alterations in physiology such as changes in cell proliferation, differentiation, migration, inflammatory mediators, and collagen production. It is supposed that these photobiomodulative effects have beneficial effects on the skin, leading to a more youthful appearance through increased collagen and elastin production, and a reduction in age spots and wrinkles. 

Key Questions 

This analysis seeks to answer the following questions:

• Which benefits with regard to skin rejuvenation result from LLLT? 

• Which risks are involved in using LLLT for skin rejuvenation (general and method-specific)?

• What are the potential risk mitigation strategies?

• Which method/device or combination of methods/devices is most effective for skin rejuvenation using LLLT?

• Which of the available devices/methods are safe for use? 

• What is the best therapeutic protocol available at the moment?  

Impatient readers may choose to skip directly to Section 6 for the conclusion and tips on practical application. 

Section 2: Methods

Analytic model

The RBA has been prepared based on the principles outlined in A Comprehensive Approach to Benefit-Risk Assessment in Drug Development (Sarac et al., 2012). 

Literature search

A literature search was conducted on Pubmed, Google Scholar, and the Cochrane Library using the search terms shown in Table 1. Titles and abstracts of the resulting studies were screened and relevant articles downloaded in full text. The references of the full-text articles were manually searched in order to identify additional trials that may have been missed by the search terms.

Inclusion criteria: We chose to include any dermatological trial conducted in humans using LLLT (any type of light source) that specified the mode of action as athermal, photobiomodulation.

Exclusion criteria: Trials that used ablative, fractional, and nonfractional lasers were excluded unless the study specified that the laser was used at settings that were nonthermal and atraumatic. We also excluded any photodynamic therapy trials that did not have a light therapy treatment only arm. 

Table 1: Literature Search 

Recommended Reading

The following sites offer information on LLLT at a consumer level and are useful as an introduction to the topic:

•  

  • Red Light Therapy Benefits - healthline.com

  • The Ultimate Guide to Red Light Therapy and Near-Infrared Light Therapy - energyblueprint.com

  • Definitive Guide to Red Light Therapy (Photobiomodulation) - trustedsupplementreviews.com
    
    

  • Yes, LED Facial Treatments Do Work (But Not In A Flash) - huffingtonpost.ca 

  • What to know about red light therapy - medicalnewstoday.com

Abbreviation list

Section 3: Existing evidence

Summary of results from clinical trials (humans)

We screened the titles/abstracts of 1836 papers identified by our search terms and included 57 clinical trials in our analysis. The remainder were excluded due to duplication or lack of relevance. The included studies used a variety of light sources (gas discharge lamps, LED) with widely differing treatment parameters making comparison difficult. Many of the studies were written by authors with a declared conflict of interest (n= 18). Several studies were small and were not placebo-controlled. The overall quality of the evidence on this topic is low, with most studies relying on subjective patient reporting or blinded photographic assessment by clinicians. 

Although our focus was on skin rejuvenation, we also included trials on other dermatological conditions treated by LLLT in order to identify potential risks and benefits beyond the condition studied. These included: 14 trials on the treatment of acne, 4 trials on actinic keratosis (a result of photoaging), 5 trials on psoriasis, and 1 trial on melasma. The trials conducted on acne were of higher quality and declared fewer conflicts of interest (2/14) than most other trials. The majority of the other disease trials were funded by device companies (actinic keratosis 4/4, psoriasis 3/5). Most trials irradiated the skin on the face only. A few trials irradiated skin on the back, arms or legs, and one trial used "full-body" irradiation. 

Table 2: Clinical Trials 

Section 4: Risk-Benefit Analysis

Decision Model

Risk and benefit criteria

The decision profile is made of up risk and benefit criteria extracted from the outcomes of the above-mentioned papers. The benefit criteria are organized by category and include the type, magnitude, and duration of the benefit as well as its perceived importance to the patient. The risk criteria are organized by category, type, severity, frequency, detectability, and mitigation. All are assigned numerical values: 

1 = low

2 = moderate

3 = high

The numerical values for both risk and benefit criteria are then summarized serving as the justification for the weighting in the following column.

Weight

The criteria are weighted on a value scale to enable comparison (based on the relative importance of a difference). Each benefit and risk criteria is assigned a weight/importance of 1 (low) 2 (medium) or 3 (high).

Weighting is independent of data sets and the final weights are based on consensus with justification based on the preceding columns of the table.

Score

Each category is assessed according to the performance of LLLT against the comparator (physiological aging) whereby a numerical value is assigned for each criterion -1 (inferior), 0 (equivalent or non-inferior) and +1 (superior) to the comparator.

Uncertainty

Uncertainty is determined according to the amount and quality of the evidence, whether it came from human or animal studies and whether methodological flaws, conflicting studies, or conflicts of interest (funding) by the authors are present. Human evidence is initially assigned a score of "1", evidence from rodent studies, "2", and in vitro or lower animal studies, "3". The uncertainty score is then adjusted by upgrading or downgrading using the above-mentioned criteria. 

Weighted score

The weights and scores are multiplied to produce weighted scores that enable direct comparison (-3 → +3) and then adjusted using the uncertainty score. Weighted scores may be upgraded where the uncertainty of the evidence is low or downgraded where the uncertainty of the evidence is high. 

Benefit assessment 

Our analysis identified a total of 28 benefits that have been documented in clinical trials to date. 

Table 3: Benefit assessment