Jule Klotter
Absorption of Sunscreen Chemicals
The skin’s ability to absorb chemicals in personal care products is well documented, as Anne Marie Fine, NMD, discussed in her June 2019 Townsend Letter article “The Skin as Exposome: An Underappreciated Route of Entry for Toxicants.” Recently, the FDA has turned its attention to the chemicals in sunscreen products. A 2020 clinical study confirms that active ingredients in commercial sunscreen products are absorbed through the skin, resulting in systemic exposure that exceeds the FDA guideline level of 0.5 ng/mL: “The 0.5 ng/mL threshold was selected because the approximated cancer risk associated with plasma concentrations below this threshold would be less than 1 in 100,000 after a single dose.” The 2020 trial follows a 2019 pilot study that measured blood levels of four chemicals (avobenzone, oxybenzone, octocrylene, and ecamsule) after exposing four groups of healthy volunteers (n=6/group) to one of four commercial sunscreens. The blood levels of these chemicals also exceeded 0.5 ng/mL.
FDA issued a proposed rule for over-the-counter sunscreens in February 2019, which would update its recommendations for sunscreen use. As part of the update process, active ingredients are to be clinically tested for systemic absorption in people exposed to maximum recommended doses. Chemicals that produce blood levels above 0.5 ng/mL are required to be tested for developmental and reproductive effects and for carcinogenicity.
The 2020 study assessed six of the 12 active ingredients that FDA has questions about. Forty-eight participants, who stayed at a clinic and out of sunlight for seven days, were randomized into groups to test four sunscreen products (a lotion, an aerosol spray, a non-aerosol spray, and a pump spray). All four products contained avobenzone and at least two other active ingredients. The product was applied once on the first day, and four times on days 2-4 at two-hour intervals (following manufacturer guidelines). After a baseline blood sample, sunscreen was applied; and an additional 12 blood samples were taken on the first day. Further samples were taken on days 2, 3, 4, 5, 6, 7, 10, 14, and 21.
Twenty-three hours after the single application on day 1, all active ingredients measured above the 0.5 ng/mL level (using geometric mean maximum plasma concentrations) in over 75% of the participants. Each of the chemicals remained above the 0.5 ng/mL level for days after the final application (on day 4) in the majority of the participants: “day 7 for avobenzone (95%; n=42/44), octisalate (75%; n=24/32, octinoxate (90%); n=18/20; day 10 for oxtocrylene (67%; n =22/33); and day 21 for homosalate (55%; n=17/31) and oxybenzone (96%); n=22/23).”
In addition, skin samples (from tape stripping) showed that all of the chemicals were still present in the skin at day 7, despite daily showers taken in the morning (after blood sampling and before the first sunscreen application) while at the clinic.
In an editorial that accompanied the 2019 pilot study, Califf and Shinkai noted that evidence of systemic absorption in humans was first shown in 1997. Over the years, some sunscreen chemicals have been linked to cancer and adverse effects on endocrine, reproductive, and developmental functions and on the environment. An FDA public advisory panel determined in 2014 that there was insufficient evidence to confirm safety for many sunscreen ingredients and formulas—despite the large body of evidence that sunscreen use prevents sunburn, precancerous actinic keratosis, and squamous cell cancer. So far, two sunscreen ingredients, zinc oxide and titanium dioxide, are recognized as “generally regarded as safe and effective” (GRASE). Two are not: para-aminobenzoic acid (PABA) and trolamine salicylate.
Califf and Shinkai raise several unanswered questions that extend beyond these initial studies on absorption such as “the effects of different sunscreen formulations, clinical characteristics (ie skin type, age, presence of skin diseases that disrupt the skin barrier), physical activity level, and exposure to sun and water on systemic sunscreen levels….” Moreover, absorption and effects may differ in infants and children compared to adults.
Califf and Shinkai say, “At a minimum, physicians should recommend use of sunscreen formulations containing GRASE ingredients such as titanium dioxide and zinc oxide as part of a larger program of photoprotection that includes seeking shade, and wearing protective clothing, hats, and sunglasses, until meaningful answers to these questions are available.”
Lycopene supplementation and eating foods high in lycopene (red tomatoes, apricots, papaya, pink grapefruit, guava, watermelon) also protect from UV damage. Tomato paste is particularly high in lycopene as cooking increases lycopene’s bioavailability.
Califf RM, Shinkai K. Filling in the Evidence About Sunscreen. JAMA. May 6, 2019.
Matta MK, et al. Effect of Sunscreen Application Under Maximal Use Conditions of Plasma Concentration of Sunscreen Active Ingredients. JAMA.i May 6, 2019.
Matta MK, et al. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients. JAMA. 202;323(3):256-267.
Stahl W, et al. Lycopene-rich products and dietary photoprotection. Photochem Photobiol Sci. 2006;5:238-242.
Evidence-Based Healthcare and Corporate Interests
The December 2, 2019, issue of the British Medical Journal contains an analysis from an international team of researchers, clinicians, regulators, and citizen advocates that discusses the need to produce “trustworthy,” corporate-free evidence for medical treatments. The problem of financial conflicts of interest is by no means a new problem. Over ten years ago in its 2009 report, the US Institute of Medicine pointed out the negative effects of accepting industry’s largesse on “‘the integrity of scientific investigations, the objectivity of medical education, and the quality of patient care, and the public’s trust in medicine.’” Nearly 60% of US medical research is sponsored by the medical industry, and numerous studies have shown that such studies tend to emphasize positive results—may even be designed to produce positive results by using comparators that make the product seem safer and more effective than it actually is. Moreover, industry-sponsored research tends to ignore negative results or possible harms. In fact, unfavorable results may not be published at all. Independent studies, unencumbered by a company’s profit-loss bottom line, tend to have more balanced views.
Even more troubling than its influence on research is the way industry has infiltrated every level of a product’s approval and recommendation process. Regulatory agencies, such as the European Medicines Agency and the US Food and Drug Administration, rely on pharmaceutical money to conduct their evaluation of new products. Many experts on panels and organizations that determine clinical guidelines and recommendations also receive funds from industry. Although these experts claim that such funding does not affect their decisions, a 2016 study shows otherwise; when conflict of interest policies are strengthened and enforced, recommendations for medical products become “less enthusiastic.” Likewise, the excessive amount of money spent on direct-to-consumer advertising, pharmaceutical “education” seminars for practitioners, and pharmaceutical representative visits to clinics benefits the companies’ bottom line more than patient health. The BMJ authors say, “Industry argues it provides valuable information that helps patients, yet a systematic review found exposure to drug company information is generally associated with prescribing more medicines, at higher costs and lower quality.”
Some European nations are looking for ways to lessen or remove corporate influence from product evaluation, regulation, and use. “Many groups are already moving away from industry influence in education and practice, but the main priority and greatest challenge is to develop models for research and evaluation independent from companies with interests in the outcomes,” say the authors. The Norwegian Medical Association no longer accepts industry-sponsored courses as accredited education. Medical journals such as PLOS Medicine and Emergency Medicine Australasia no longer take pharmaceutical advertising. For the past decade, the Italian government has taxed drug companies to obtain money that pays for public interest research. Last year, the UK Labour Party proposed a plan to use government funding for late-stage clinical trials and to set up state-owned pharmaceutical companies. US politicians proposed a system five decades ago in which public regulators would assign independent research teams to perform product testing that is funded by the product’s company. Not surprisingly, industry lobbyists have blocked this idea—at least so far.
Corporate influence in medical care, however, is just the tip of the healthcare iceberg in my view. The regulation of environmental chemicals that have major impacts on health is subject to the same type of corporate influence. Many of these chemicals are known to adversely affect health, yet government agencies continue to whitewash the information to downplay the harms. Linda Birnbaum, former director of the National Institute of Environmental Health Sciences and the National Toxicology Program, recently stated that PFAS (per- and polyfluoroalkyl substances) cause immune dysfunction, elevated cholesterol levels, kidney cancer, weight gain, liver dysfunction, and reproductive problems. PFAS are used in stain- and water-repellant fabric, Teflon and non-stick materials, fire-fighting foam, and food packaging and widely contaminate drinking water and soil.
In an interview with Sharon Lerner at The Intercept, Birnbaum, now retired, said that she was told by the NIH deputy director to use “associated with” rather than “cause”—despite a body of over 800 studies, including longitudinal studies and studies with diverse populations, that all revealed the same adverse effects and despite laboratory studies that “show the mechanism through which PFAS chemicals cause harm in people.” After co-authoring an editorial in PLOS Biology (December 18, 2017),Birnbaum was targeted by politicians and NIH superiors with more restrictions: “’Everything I did required clearance. Even in my lab,’” she told Lerner. She was denied a salary increase and threatened with the loss of her job. Her 2017 editorial concludes: “Closing the gap between evidence and policy will require that engaged citizens, both scientists and nonscientists, work to ensure our government officials pass health-protective policies based on the best available scientific evidence.”
Gross L, Birnbaum LS. Regulating toxic chemicals for public and environmental health. PLOS Biology. December 18, 2017.
Lerner S. Top US Toxicologist Was Barred From Saying PFAS Cause Disease in Humans. She’s Saying It Now. The Intercept. October 24, 2019.
Moynihan R, et al. Pathways to independence: towards producing and using trustworthy evidence. BMJ. 2019;367;16576.
Saffron and Macular Degeneration
Antioxidants, including vitamins C, E, lutein, and zeaxanthin, can slow the progression of age-related macular degeneration (AMD) by protecting against oxidative stress that damages retinal cells; but saffron works as an antioxidant and more. A 2019 Italian study reports that the spice saffron (derived from the Crocus sativus flower) is even more effective in protecting vision. The researchers conducted a study on Sprague-Dawley adult rats and a longitudinal open-label study with AMD patients. The human study compared saffron-treated patients to lutein/zeaxanthin-treated patients while the animal study looked at saffron’s effects on morphology, immunohistochemistry, and enzyme activity in animals exposed to intense, vision-damaging light.
The rat study showed that saffron acts as an antioxidant but also regulates gene expression, modulating metalloproteinase expression and enzyme activity. Rats treated with saffron before light exposure had far less retinal damage than untreated rats, “in a range comparable to the [unexposed] healthy control.”
In the human trial, the vision of AMD patients treated with saffron (n=23) was stable while the vision in the lutein/zeaxanthin group (n=19) had declined after 29 months (±5) months. Patients were assessed with clinical exams and Focal (macular) electroretinogram to estimate flicker sensitivity. The authors conclude, “Patients treated with the AREDS protocol (lutein/zeaxanthin) present a deterioration of retinal function whereas saffron treated patients showed quite a stable response over time; altogether these results suggest that saffron is more powerful in slowing down the progression of the disease compared to the widely employed standard AREDS supplement.” The authors say this study is preliminary and needs to be confirmed with larger trials.
DiMarco S, et al. Saffron: A Multitask Neuroprotective Agent for Retinal Degenerative Diseases. Antioxidants. 2019;8:224.
Relationship Between Atopic Dermatitis and Food Allergies
A 2016 British systematic review of 66 studies found “a strong and dose-dependent association” between atopic dermatitis (AD), food allergy (FA), and food sensitization. The studies were too diverse to perform a meta-analysis: 18 were population-based, eight had high-risk cohorts, and the remainder focused on patients with established AD or FA. Early onset, severity, and increased persistence of AD correlated to increased risk of food allergy in multiple studies. The authors report, “…in population-based studies, the likelihood of food sensitization was up to 6 times higher in patients with AD versus healthy control subjects at 3 months of age (odds ratio, 6.18;95% CI, 2.94-12.98; P<.001).”
Interestingly, the authors say clinical food allergy—particularly to egg and peanuts—can occur without a child ever eating the food. Evidence indicates that “it is likely that food sensitization occurs primarily across the inflamed skin barrier in eczematous skin.” The authors refer to a study in which the presence of food protein in dust samples taken from a baby’s home was associated with food sensitization, particularly if the baby had eczema. Also, in a lab experiment, mice were repeatedly given ovalbumin and cholera toxin orally over eight weeks or ovalbumin was repeatedly applied to tape-stripped skin over seven weeks: “Both…demonstrated sIgE antibody responses, and yet only those without oral immunization had signs in keeping with anaphylaxis on oral challenge.”
If skin health is a major factor in the development of food allergies, the authors say, “environmental factors, such as water hardness, the use of soaps and detergents, and the frequency of washing, could further contribute to skin barrier permeability and thus food sensitization.”
Tsakok T, et al.Does atopic dermatitis cause food allergy? A systematic review. I J Allergy Clin Immunol. April 2016.
This column originally appeared in Townsend Letter (April 2020).
Published April 20, 2024
About the Author
Jule Klotter has a master’s in professional writing from the University of Southern California. She joined Townsend Letter’s staff in 1990. Over the years, she has written abstract articles for “Shorts” and many book reviews that provide information for busy practitioners. She became Townsend Letter’s editor near the end of 2016.