Yssra S. Soliman, BA

The connection between diet and physical beauty has been an area of increasing interest in popular culture as well as in the scientific community. Numerous supplements, plant derivatives, and antioxidants have been proposed to help improve skin conditions and prevent signs of aging.¹ Clinical and basic research has played an important role in confirming or debunking these claims, leading to new insight into oral supplements that may play a role in improving signs of photoaging, as well as symptoms of common skin diseases such as acne vulgaris (AV), atopic dermatitis (AD), and psoriasis. This article reviews some of the vitamins, supplements, and antioxidants that have been studied in the improvement of these conditions.

Photoaging

Recently, there has been increased interest among researchers in the role of antioxidants in combatting photoaging. The main determinants of photoaging are chronic sunlight exposure and melanin density. Photoaging presentation includes deep rhytides, pigmentary changes, dryness, loss of skin tone, leathery appearance, and actinic purpura.^2-4

Beta-carotene is a fat-soluble derivative of vitamin A, which has retinol activity and has an inhibitory effect on free radicals. It has been used to decrease the effect of UV light on the skin as well as to treat erythropoietic porphyria.^5-7 One study evaluated the efficacy of low-dose and high-dose beta-carotene in improving facial rhytides and elasticity in a cohort of 30 women older than 50 years.⁸ Participants were given 30 or 90 mg of beta-carotene once daily for 90 days, and the final results were compared to baseline. Those who received the 30-mg dose showed improvements in facial rhytides and elasticity, increased type I procollagen messenger RNA levels, decreased UV-induced thymine dimer staining, and decreased 8-hydroxy-2′-deoxyguanosine staining. The lower dose of beta-carotene was found to prevent photoaging and was superior to the higher dose, which actually significantly decreased the minimal erythema dose (indicating a deleterious effect)(P=.025).⁸

Another study compared the role of a 25-mg carotenoid supplement vs a combination of carotenoid and vitamin E (335 mg [500 IU] RRR-α-tocopherol) supplements in preventing erythema development on the back.⁹ Using a blue light solar stimulator for illumination, erythema on the dorsal back skin was significantly reduced after week 8 (P<.01). The erythema was lower in the combination group than the carotenoid group alone, but the difference was not statistically significant. Furthermore, after 12 weeks, yellowing of the skin was observed in both groups, especially the skin of the palms and face.⁹

Collagen peptides also have been used in the prevention and repair of photoaging. Proksch et al¹⁰ conducted a double-blind, placebo-controlled trial to investigate the role of collagen peptides on skin elasticity in 69 women aged 35 to 55 years. At 4 weeks, oral supplementation of collagen hydrolysate (2.5 g once daily or 5 g once daily for 8 weeks) showed significant (P<.05) improvement of skin elasticity in both the low-dose and high-dose groups in women older than 50 years; however, collagen peptides did not lead to statistically significant improvement in skin hydration or transepidermal water loss. No known side effects were reported; thus, collagen peptides may be both efficacious and safe in improving signs of photoaging in elderly patients.¹⁰ Thus, these studies have shown potentially positive effects of beta-carotene, vitamin E, and collagen peptides in improving the signs of photoaging.

Acne Vulgaris

Acne vulgaris is a common dermatologic condition seen in the western hemisphere, with 40 to 50 million affected individuals in the United States annually.^11,12 A landmark study that examined 1200 Kitavans from Papua New Guinea and 115 Aché individuals from a hunter-gatherer community in Paraguay found no cases of AV in either group.¹² These findings have led to the speculation that AV may be associated with environmental factors, particularly the Western diet.

An investigator-blinded randomized clinical trial (RCT) explored the role of a low-glycemic diet compared to a carbohydrate-dense diet on improvement of AV lesions after 12 weeks.¹³ The results yielded a significant decrease in lesions in the low-glycemic group (mean [SEM], −23.5 [−3.9]) vs the control group (−12.0 [−3.0])(P=.03). Furthermore, the results indicated a significant decrease in weight (P<.001) and body mass index (P=.001) with an improvement in insulin sensitivity in the low-glycemic group vs the control group.¹³ Kwon et al¹⁴ conducted a similar investigator-blinded parallel study with 32 participants receiving either a low-glycemic diet or continuing their normal diet for 10 weeks. Participants in the low-glycemic group demonstrated a significant reduction in mean noninflammatory lesions (−27.6% [P=.04]) and mean inflammatory lesions (−70.9% [P<.05]). Histologic image analysis showed a significant decrease in the mean (SEM) area of sebaceous glands in the low-glycemic group (0.32 [0.03] mm²) compared to baseline (0.24 [0.03] mm²)(P=.03). At 10 weeks, immunohistochemical specimens showed reduction in IL-8 (P=.03) and sterol regulatory element-binding protein 1 (P=.03), which regulates the synthesis of lipids.¹⁴ Thus, both studies concluded that a reduction in glycemic load may improve acne overall.^13,14

Another study attempted to investigate the role of additional dietary supplements in improving acne. A double-blinded RCT explored the efficacy of omega-3 fatty acids or γ-linoleic acid compared to a control group in improving mild to moderate AV lesions through clinical and histological evaluations.¹⁵ The 10-week prospective study included 45 patients who were allocated to 3 matched groups and randomized to 3 treatment arms. They were given omega-3 fatty acids (1000 mg each of eicosapentaenoic acid and docosahexaenoic acid) or γ-linoleic acid (borage oil with 400 mg of γ-linoleic acid) or no intervention. After treatment completion, patients in both treatment groups showed significant reduction in mean inflammatory acne lesions, mean noninflammatory acne lesions, and mean acne severity (all P<.05), while the control group showed no significant reduction in acne lesions or acne severity. Furthermore, hematoxylin and eosin and IL-8 immunohistochemical staining of biopsies from the affected areas showed significant reduction of inflammation in both treatment groups (P<.05) but not in the control group. Therefore, the authors concluded that both omega-3 fatty acids and γ-linoleic acid could be used as adjuvant therapies in AV treatment.¹⁵

Atopic Dermatitis

The prevalence of atopic dermatitis (AD) in children ranges from approximately 9% to 18% across the United States.¹⁶ Pyridoxine, or vitamin B₆, is an important water-soluble vitamin and a cofactor for numerous biochemical processes including carbohydrate and amino acid metabolism pathways and glucocorticoid receptor regulation.^17,18 However, a double-blinded, placebo-controlled RCT failed to show efficacy of once-daily pyridoxine hydrochloride 50 mg in improving erythema, itching, or nocturnal sleep disturbance associated with AD in a cohort of 48 children. The investigators concluded that pyridoxine supplementation cannot be recommended to improve the symptoms of AD in children.¹⁹

Zinc is an essential nutrient that functions as an important cofactor in cell metabolism and growth pathways.²⁰ One study showed that intracellular erythrocyte zinc levels were significantly lower in AD patients compared to healthy controls (P<.001); however, there was no observed difference in serum zinc levels (P=.148). Furthermore, greater disease severity as determined by the SCORing Atopic Dermatitis (SCORAD) index was negatively correlated with erythrocyte zinc levels (r=−0.791; P<.001).²¹ Kim et al²² investigated hair zinc levels and the efficacy of oral zinc supplementation in children with mild to moderate AD. Mean (SD) hair zinc levels were lower in the AD group compared to the control group (113.10 [33.6] μg vs 130.90 [36.63] μg [P=.012]). Of 41 AD patients with low zinc levels, 22 were allocated to group A, which received oral zinc oxide 12 mg for 8 weeks, and 19 were allocated to group B, which did not receive any supplementation over the same period. Groups A and B also received oral antihistamines and topical moisturizers. Mean (SD) zinc levels increased significantly in group A from 96.36 (21.05) μg to 131.81 (27.45) μg (P<.001). Furthermore, relative to group B, group A showed significantly greater improvements in eczema area and severity index (P=.044), transepidermal water loss (P=.015), and visual analog scale for pruritus (P<.001) at the end of 8 weeks. The authors concluded that oral zinc supplementation might be an effective adjunctive therapy for AD patients with low hair zinc levels.²²

Researchers also have explored the efficacy of fat-soluble vitamins D and E in treating AD. Vitamin D is thought to downregulate IgE-mediated skin reactions and decrease adverse effects of UV light on the skin.^23,24 A double-blind, placebo-controlled trial randomized 45 patients with AD to 4 groups: vitamins D and E placebos (n=11), 1600 IU vitamin D₃ plus vitamin E placebo (n=12), 600 IU vitamin E (synthetic all-rac-α-tocopherol) plus vitamin D placebo (n=11), and 1600 IU vitamin D₃ plus 600 IU vitamin E (synthetic all-rac-α-tocopherol)(n=11).²⁵ After 60 days, the SCORAD index was reduced by 28.9% in the placebo group, 34.8% in the vitamin D₃ group, 35.7% in the vitamin E group, and 64.3% in the combined vitamins D and E group (P=.004). Furthermore, prior to intervention, a negative correlation was demonstrated between plasma α-tocopherol concentration and the SCORAD index (r=−.33; P=.025).²⁵ Thus, supplementing vitamins D and E may play a beneficial role in the treatment of AD.

Other emerging studies are investigating the role of the gut microbiome in various pathologies. Prebiotics may alter the gut microbiome and are thought to play a role in reducing intestinal inflammation.²⁶ One randomized, placebo-controlled, parallel study examined the effect of prebiotic oligosaccharide supplementation on the development of AD in at-risk children, defined as having a biological parent with a history of asthma, allergic rhinitis, or AD.²⁷ At 6-month follow-up, 10 infants (9.8%)(95% CI, 5.4%-17.1%) in the intervention group (n=102) and 24 infants (23.1%)(95% CI, 16.0%-32.1%) in the placebo group (n=104) had developed AD. The authors postulated that the prebiotic oligosaccharides might play a role in immune modulation by altering bowel flora and preventing the development of AD in infancy.²⁷

Notably, a 2012 Cochrane review evaluated 11 studies of dietary supplements as possible treatment options for AD. The authors concluded that the evidence was minimal to support the regular use of dietary supplements, especially due to their high cost as well as the possibility that high levels of certain vitamins (eg, vitamin D) may cause long-term complications.²⁶

Psoriasis

Psoriasis is an autoimmune skin condition that has an annual prevalence ranging from approximately 1% to 9% in adults residing in Western countries.^28,29 Some have argued that due to decreased bacterial diversity and increased bacterial growth in the small bowel, psoriatic patients are exposed to higher levels of bacterial peptidoglycans and endotoxins.³⁰ To combat the absorption of these substances in psoriasis patients, we advocate for a vegetarian diet with low fats, limited alcohol consumption, and supplements of bile acids and bioflavonoid.

The effects of very long chain fatty acids also have been examined. A 4-month, double-blind, multicenter RCT compared the effects of daily supplementation with 6 g of either omega-3 fatty acids or omega-6 fatty acids in patients with mild to moderate plaque psoriasis.³¹ Psoriasis area and severity index scores and patient subjective scores did not change significantly in either group; however, scaling was reduced in both groups (P<.01). The group receiving omega-3 fatty acids had decreased cellular infiltration (P<.01), and the group receiving omega-6 fatty acids had decreased desquamation and redness (P<.05). In the omega-6 group, there was a significant correlation between clinical improvement (decrease in clinical score) and increase in serum eicosapentaenoic acid (r=−0.34; P<.05) and total omega-3 fatty acids (r=−0.36; P<.05). Overall, the authors concluded that supplementation with omega-3 fatty acids (fish oil) was no better than omega-6 fatty acids (corn oil) for treatment of psoriasis.³¹

Some dermatologists have advocated for the use of oral vitamin D supplementation as an adjunctive treatment of psoriasis, given that it is inexpensive and also may play a role in reducing the risk for cancer and cardiovascular events.³² One study evaluated the level of 25-hydroxy vitamin D in 43 psoriasis patients compared to 43 healthy controls. Mean (SD) vitamin D levels were significantly lower in psoriasis patients (13.3 [6.9]) compared to controls (22.4 [18.4])(P=.004).³³ A cross-sectional study similarly found significantly higher rates of vitamin D deficiency (25-hydroxy vitamin D <20 ng/mL) in psoriatic patients (57.8%) compared to patients with rheumatoid arthritis (37.5%) and healthy controls (29.7%)(P<.001). Interestingly, during winter the prevalence of vitamin D deficiency increased to 80.9%, 41.3%, and 30.3% in the 3 groups, respectively; however, no significant correlation was seen between psoriasis severity, as measured by psoriasis area and severity index, and serum vitamin D levels.³⁴ Although vitamin D deficiency may be more prevalent among patients with psoriasis, data regarding the efficacy of treating psoriasis with oral vitamin D supplementation is still lacking.

Conclusion

Our understanding of the link between diet and dermatologic conditions continues to evolve. Recent data for several dietary supplements and therapies showed promising results in repairing signs of photoaging, as well as treating AV, AD, and psoriasis. As patients seek these adjunctive therapies, it is important for physicians to be well informed on the benefits and risks to appropriately counsel patients.

Globally, physicians advocate for a low-glycemic diet rich in fruits and vegetables. Furthermore, the cosmetic diet can be enhanced by the consumption of dietary supplements such as beta-carotene, collagen peptides, zinc, and fat-soluble vitamins such as vitamins D and E. However, prospective RCTs are needed to further investigate the role of these dietary elements in treating and improving dermatologic conditions.

The connection between diet and physical beauty has been an area of increasing interest in popular culture as well as in the scientific community. Numerous supplements, plant derivatives, and antioxidants have been proposed to help improve skin conditions and prevent signs of aging.¹ Clinical and basic research has played an important role in confirming or debunking these claims, leading to new insight into oral supplements that may play a role in improving signs of photoaging, as well as symptoms of common skin diseases such as acne vulgaris (AV), atopic dermatitis (AD), and psoriasis. This article reviews some of the vitamins, supplements, and antioxidants that have been studied in the improvement of these conditions.

Photoaging

Recently, there has been increased interest among researchers in the role of antioxidants in combatting photoaging. The main determinants of photoaging are chronic sunlight exposure and melanin density. Photoaging presentation includes deep rhytides, pigmentary changes, dryness, loss of skin tone, leathery appearance, and actinic purpura.^2-4

Beta-carotene is a fat-soluble derivative of vitamin A, which has retinol activity and has an inhibitory effect on free radicals. It has been used to decrease the effect of UV light on the skin as well as to treat erythropoietic porphyria.^5-7 One study evaluated the efficacy of low-dose and high-dose beta-carotene in improving facial rhytides and elasticity in a cohort of 30 women older than 50 years.⁸ Participants were given 30 or 90 mg of beta-carotene once daily for 90 days, and the final results were compared to baseline. Those who received the 30-mg dose showed improvements in facial rhytides and elasticity, increased type I procollagen messenger RNA levels, decreased UV-induced thymine dimer staining, and decreased 8-hydroxy-2′-deoxyguanosine staining. The lower dose of beta-carotene was found to prevent photoaging and was superior to the higher dose, which actually significantly decreased the minimal erythema dose (indicating a deleterious effect)(P=.025).⁸

Another study compared the role of a 25-mg carotenoid supplement vs a combination of carotenoid and vitamin E (335 mg [500 IU] RRR-α-tocopherol) supplements in preventing erythema development on the back.⁹ Using a blue light solar stimulator for illumination, erythema on the dorsal back skin was significantly reduced after week 8 (P<.01). The erythema was lower in the combination group than the carotenoid group alone, but the difference was not statistically significant. Furthermore, after 12 weeks, yellowing of the skin was observed in both groups, especially the skin of the palms and face.⁹

Collagen peptides also have been used in the prevention and repair of photoaging. Proksch et al¹⁰ conducted a double-blind, placebo-controlled trial to investigate the role of collagen peptides on skin elasticity in 69 women aged 35 to 55 years. At 4 weeks, oral supplementation of collagen hydrolysate (2.5 g once daily or 5 g once daily for 8 weeks) showed significant (P<.05) improvement of skin elasticity in both the low-dose and high-dose groups in women older than 50 years; however, collagen peptides did not lead to statistically significant improvement in skin hydration or transepidermal water loss. No known side effects were reported; thus, collagen peptides may be both efficacious and safe in improving signs of photoaging in elderly patients.¹⁰ Thus, these studies have shown potentially positive effects of beta-carotene, vitamin E, and collagen peptides in improving the signs of photoaging.

Acne Vulgaris

Acne vulgaris is a common dermatologic condition seen in the western hemisphere, with 40 to 50 million affected individuals in the United States annually.^11,12 A landmark study that examined 1200 Kitavans from Papua New Guinea and 115 Aché individuals from a hunter-gatherer community in Paraguay found no cases of AV in either group.¹² These findings have led to the speculation that AV may be associated with environmental factors, particularly the Western diet.

An investigator-blinded randomized clinical trial (RCT) explored the role of a low-glycemic diet compared to a carbohydrate-dense diet on improvement of AV lesions after 12 weeks.¹³ The results yielded a significant decrease in lesions in the low-glycemic group (mean [SEM], −23.5 [−3.9]) vs the control group (−12.0 [−3.0])(P=.03). Furthermore, the results indicated a significant decrease in weight (P<.001) and body mass index (P=.001) with an improvement in insulin sensitivity in the low-glycemic group vs the control group.¹³ Kwon et al¹⁴ conducted a similar investigator-blinded parallel study with 32 participants receiving either a low-glycemic diet or continuing their normal diet for 10 weeks. Participants in the low-glycemic group demonstrated a significant reduction in mean noninflammatory lesions (−27.6% [P=.04]) and mean inflammatory lesions (−70.9% [P<.05]). Histologic image analysis showed a significant decrease in the mean (SEM) area of sebaceous glands in the low-glycemic group (0.32 [0.03] mm²) compared to baseline (0.24 [0.03] mm²)(P=.03). At 10 weeks, immunohistochemical specimens showed reduction in IL-8 (P=.03) and sterol regulatory element-binding protein 1 (P=.03), which regulates the synthesis of lipids.¹⁴ Thus, both studies concluded that a reduction in glycemic load may improve acne overall.^13,14

Another study attempted to investigate the role of additional dietary supplements in improving acne. A double-blinded RCT explored the efficacy of omega-3 fatty acids or γ-linoleic acid compared to a control group in improving mild to moderate AV lesions through clinical and histological evaluations.¹⁵ The 10-week prospective study included 45 patients who were allocated to 3 matched groups and randomized to 3 treatment arms. They were given omega-3 fatty acids (1000 mg each of eicosapentaenoic acid and docosahexaenoic acid) or γ-linoleic acid (borage oil with 400 mg of γ-linoleic acid) or no intervention. After treatment completion, patients in both treatment groups showed significant reduction in mean inflammatory acne lesions, mean noninflammatory acne lesions, and mean acne severity (all P<.05), while the control group showed no significant reduction in acne lesions or acne severity. Furthermore, hematoxylin and eosin and IL-8 immunohistochemical staining of biopsies from the affected areas showed significant reduction of inflammation in both treatment groups (P<.05) but not in the control group. Therefore, the authors concluded that both omega-3 fatty acids and γ-linoleic acid could be used as adjuvant therapies in AV treatment.¹⁵

Atopic Dermatitis

The prevalence of atopic dermatitis (AD) in children ranges from approximately 9% to 18% across the United States.¹⁶ Pyridoxine, or vitamin B₆, is an important water-soluble vitamin and a cofactor for numerous biochemical processes including carbohydrate and amino acid metabolism pathways and glucocorticoid receptor regulation.^17,18 However, a double-blinded, placebo-controlled RCT failed to show efficacy of once-daily pyridoxine hydrochloride 50 mg in improving erythema, itching, or nocturnal sleep disturbance associated with AD in a cohort of 48 children. The investigators concluded that pyridoxine supplementation cannot be recommended to improve the symptoms of AD in children.¹⁹

Zinc is an essential nutrient that functions as an important cofactor in cell metabolism and growth pathways.²⁰ One study showed that intracellular erythrocyte zinc levels were significantly lower in AD patients compared to healthy controls (P<.001); however, there was no observed difference in serum zinc levels (P=.148). Furthermore, greater disease severity as determined by the SCORing Atopic Dermatitis (SCORAD) index was negatively correlated with erythrocyte zinc levels (r=−0.791; P<.001).²¹ Kim et al²² investigated hair zinc levels and the efficacy of oral zinc supplementation in children with mild to moderate AD. Mean (SD) hair zinc levels were lower in the AD group compared to the control group (113.10 [33.6] μg vs 130.90 [36.63] μg [P=.012]). Of 41 AD patients with low zinc levels, 22 were allocated to group A, which received oral zinc oxide 12 mg for 8 weeks, and 19 were allocated to group B, which did not receive any supplementation over the same period. Groups A and B also received oral antihistamines and topical moisturizers. Mean (SD) zinc levels increased significantly in group A from 96.36 (21.05) μg to 131.81 (27.45) μg (P<.001). Furthermore, relative to group B, group A showed significantly greater improvements in eczema area and severity index (P=.044), transepidermal water loss (P=.015), and visual analog scale for pruritus (P<.001) at the end of 8 weeks. The authors concluded that oral zinc supplementation might be an effective adjunctive therapy for AD patients with low hair zinc levels.²²

Researchers also have explored the efficacy of fat-soluble vitamins D and E in treating AD. Vitamin D is thought to downregulate IgE-mediated skin reactions and decrease adverse effects of UV light on the skin.^23,24 A double-blind, placebo-controlled trial randomized 45 patients with AD to 4 groups: vitamins D and E placebos (n=11), 1600 IU vitamin D₃ plus vitamin E placebo (n=12), 600 IU vitamin E (synthetic all-rac-α-tocopherol) plus vitamin D placebo (n=11), and 1600 IU vitamin D₃ plus 600 IU vitamin E (synthetic all-rac-α-tocopherol)(n=11).²⁵ After 60 days, the SCORAD index was reduced by 28.9% in the placebo group, 34.8% in the vitamin D₃ group, 35.7% in the vitamin E group, and 64.3% in the combined vitamins D and E group (P=.004). Furthermore, prior to intervention, a negative correlation was demonstrated between plasma α-tocopherol concentration and the SCORAD index (r=−.33; P=.025).²⁵ Thus, supplementing vitamins D and E may play a beneficial role in the treatment of AD.

Other emerging studies are investigating the role of the gut microbiome in various pathologies. Prebiotics may alter the gut microbiome and are thought to play a role in reducing intestinal inflammation.²⁶ One randomized, placebo-controlled, parallel study examined the effect of prebiotic oligosaccharide supplementation on the development of AD in at-risk children, defined as having a biological parent with a history of asthma, allergic rhinitis, or AD.²⁷ At 6-month follow-up, 10 infants (9.8%)(95% CI, 5.4%-17.1%) in the intervention group (n=102) and 24 infants (23.1%)(95% CI, 16.0%-32.1%) in the placebo group (n=104) had developed AD. The authors postulated that the prebiotic oligosaccharides might play a role in immune modulation by altering bowel flora and preventing the development of AD in infancy.²⁷

Notably, a 2012 Cochrane review evaluated 11 studies of dietary supplements as possible treatment options for AD. The authors concluded that the evidence was minimal to support the regular use of dietary supplements, especially due to their high cost as well as the possibility that high levels of certain vitamins (eg, vitamin D) may cause long-term complications.²⁶

Psoriasis

Psoriasis is an autoimmune skin condition that has an annual prevalence ranging from approximately 1% to 9% in adults residing in Western countries.^28,29 Some have argued that due to decreased bacterial diversity and increased bacterial growth in the small bowel, psoriatic patients are exposed to higher levels of bacterial peptidoglycans and endotoxins.³⁰ To combat the absorption of these substances in psoriasis patients, we advocate for a vegetarian diet with low fats, limited alcohol consumption, and supplements of bile acids and bioflavonoid.

The effects of very long chain fatty acids also have been examined. A 4-month, double-blind, multicenter RCT compared the effects of daily supplementation with 6 g of either omega-3 fatty acids or omega-6 fatty acids in patients with mild to moderate plaque psoriasis.³¹ Psoriasis area and severity index scores and patient subjective scores did not change significantly in either group; however, scaling was reduced in both groups (P<.01). The group receiving omega-3 fatty acids had decreased cellular infiltration (P<.01), and the group receiving omega-6 fatty acids had decreased desquamation and redness (P<.05). In the omega-6 group, there was a significant correlation between clinical improvement (decrease in clinical score) and increase in serum eicosapentaenoic acid (r=−0.34; P<.05) and total omega-3 fatty acids (r=−0.36; P<.05). Overall, the authors concluded that supplementation with omega-3 fatty acids (fish oil) was no better than omega-6 fatty acids (corn oil) for treatment of psoriasis.³¹

Some dermatologists have advocated for the use of oral vitamin D supplementation as an adjunctive treatment of psoriasis, given that it is inexpensive and also may play a role in reducing the risk for cancer and cardiovascular events.³² One study evaluated the level of 25-hydroxy vitamin D in 43 psoriasis patients compared to 43 healthy controls. Mean (SD) vitamin D levels were significantly lower in psoriasis patients (13.3 [6.9]) compared to controls (22.4 [18.4])(P=.004).³³ A cross-sectional study similarly found significantly higher rates of vitamin D deficiency (25-hydroxy vitamin D <20 ng/mL) in psoriatic patients (57.8%) compared to patients with rheumatoid arthritis (37.5%) and healthy controls (29.7%)(P<.001). Interestingly, during winter the prevalence of vitamin D deficiency increased to 80.9%, 41.3%, and 30.3% in the 3 groups, respectively; however, no significant correlation was seen between psoriasis severity, as measured by psoriasis area and severity index, and serum vitamin D levels.³⁴ Although vitamin D deficiency may be more prevalent among patients with psoriasis, data regarding the efficacy of treating psoriasis with oral vitamin D supplementation is still lacking.

Conclusion

Our understanding of the link between diet and dermatologic conditions continues to evolve. Recent data for several dietary supplements and therapies showed promising results in repairing signs of photoaging, as well as treating AV, AD, and psoriasis. As patients seek these adjunctive therapies, it is important for physicians to be well informed on the benefits and risks to appropriately counsel patients.

Globally, physicians advocate for a low-glycemic diet rich in fruits and vegetables. Furthermore, the cosmetic diet can be enhanced by the consumption of dietary supplements such as beta-carotene, collagen peptides, zinc, and fat-soluble vitamins such as vitamins D and E. However, prospective RCTs are needed to further investigate the role of these dietary elements in treating and improving dermatologic conditions.

The connection between diet and physical beauty has been an area of increasing interest in popular culture as well as in the scientific community. Numerous supplements, plant derivatives, and antioxidants have been proposed to help improve skin conditions and prevent signs of aging.¹ Clinical and basic research has played an important role in confirming or debunking these claims, leading to new insight into oral supplements that may play a role in improving signs of photoaging, as well as symptoms of common skin diseases such as acne vulgaris (AV), atopic dermatitis (AD), and psoriasis. This article reviews some of the vitamins, supplements, and antioxidants that have been studied in the improvement of these conditions.

Photoaging

Recently, there has been increased interest among researchers in the role of antioxidants in combatting photoaging. The main determinants of photoaging are chronic sunlight exposure and melanin density. Photoaging presentation includes deep rhytides, pigmentary changes, dryness, loss of skin tone, leathery appearance, and actinic purpura.^2-4

Beta-carotene is a fat-soluble derivative of vitamin A, which has retinol activity and has an inhibitory effect on free radicals. It has been used to decrease the effect of UV light on the skin as well as to treat erythropoietic porphyria.^5-7 One study evaluated the efficacy of low-dose and high-dose beta-carotene in improving facial rhytides and elasticity in a cohort of 30 women older than 50 years.⁸ Participants were given 30 or 90 mg of beta-carotene once daily for 90 days, and the final results were compared to baseline. Those who received the 30-mg dose showed improvements in facial rhytides and elasticity, increased type I procollagen messenger RNA levels, decreased UV-induced thymine dimer staining, and decreased 8-hydroxy-2′-deoxyguanosine staining. The lower dose of beta-carotene was found to prevent photoaging and was superior to the higher dose, which actually significantly decreased the minimal erythema dose (indicating a deleterious effect)(P=.025).⁸

Another study compared the role of a 25-mg carotenoid supplement vs a combination of carotenoid and vitamin E (335 mg [500 IU] RRR-α-tocopherol) supplements in preventing erythema development on the back.⁹ Using a blue light solar stimulator for illumination, erythema on the dorsal back skin was significantly reduced after week 8 (P<.01). The erythema was lower in the combination group than the carotenoid group alone, but the difference was not statistically significant. Furthermore, after 12 weeks, yellowing of the skin was observed in both groups, especially the skin of the palms and face.⁹

Collagen peptides also have been used in the prevention and repair of photoaging. Proksch et al¹⁰ conducted a double-blind, placebo-controlled trial to investigate the role of collagen peptides on skin elasticity in 69 women aged 35 to 55 years. At 4 weeks, oral supplementation of collagen hydrolysate (2.5 g once daily or 5 g once daily for 8 weeks) showed significant (P<.05) improvement of skin elasticity in both the low-dose and high-dose groups in women older than 50 years; however, collagen peptides did not lead to statistically significant improvement in skin hydration or transepidermal water loss. No known side effects were reported; thus, collagen peptides may be both efficacious and safe in improving signs of photoaging in elderly patients.¹⁰ Thus, these studies have shown potentially positive effects of beta-carotene, vitamin E, and collagen peptides in improving the signs of photoaging.

Acne Vulgaris

Acne vulgaris is a common dermatologic condition seen in the western hemisphere, with 40 to 50 million affected individuals in the United States annually.^11,12 A landmark study that examined 1200 Kitavans from Papua New Guinea and 115 Aché individuals from a hunter-gatherer community in Paraguay found no cases of AV in either group.¹² These findings have led to the speculation that AV may be associated with environmental factors, particularly the Western diet.

An investigator-blinded randomized clinical trial (RCT) explored the role of a low-glycemic diet compared to a carbohydrate-dense diet on improvement of AV lesions after 12 weeks.¹³ The results yielded a significant decrease in lesions in the low-glycemic group (mean [SEM], −23.5 [−3.9]) vs the control group (−12.0 [−3.0])(P=.03). Furthermore, the results indicated a significant decrease in weight (P<.001) and body mass index (P=.001) with an improvement in insulin sensitivity in the low-glycemic group vs the control group.¹³ Kwon et al¹⁴ conducted a similar investigator-blinded parallel study with 32 participants receiving either a low-glycemic diet or continuing their normal diet for 10 weeks. Participants in the low-glycemic group demonstrated a significant reduction in mean noninflammatory lesions (−27.6% [P=.04]) and mean inflammatory lesions (−70.9% [P<.05]). Histologic image analysis showed a significant decrease in the mean (SEM) area of sebaceous glands in the low-glycemic group (0.32 [0.03] mm²) compared to baseline (0.24 [0.03] mm²)(P=.03). At 10 weeks, immunohistochemical specimens showed reduction in IL-8 (P=.03) and sterol regulatory element-binding protein 1 (P=.03), which regulates the synthesis of lipids.¹⁴ Thus, both studies concluded that a reduction in glycemic load may improve acne overall.^13,14

Another study attempted to investigate the role of additional dietary supplements in improving acne. A double-blinded RCT explored the efficacy of omega-3 fatty acids or γ-linoleic acid compared to a control group in improving mild to moderate AV lesions through clinical and histological evaluations.¹⁵ The 10-week prospective study included 45 patients who were allocated to 3 matched groups and randomized to 3 treatment arms. They were given omega-3 fatty acids (1000 mg each of eicosapentaenoic acid and docosahexaenoic acid) or γ-linoleic acid (borage oil with 400 mg of γ-linoleic acid) or no intervention. After treatment completion, patients in both treatment groups showed significant reduction in mean inflammatory acne lesions, mean noninflammatory acne lesions, and mean acne severity (all P<.05), while the control group showed no significant reduction in acne lesions or acne severity. Furthermore, hematoxylin and eosin and IL-8 immunohistochemical staining of biopsies from the affected areas showed significant reduction of inflammation in both treatment groups (P<.05) but not in the control group. Therefore, the authors concluded that both omega-3 fatty acids and γ-linoleic acid could be used as adjuvant therapies in AV treatment.¹⁵

Atopic Dermatitis

The prevalence of atopic dermatitis (AD) in children ranges from approximately 9% to 18% across the United States.¹⁶ Pyridoxine, or vitamin B₆, is an important water-soluble vitamin and a cofactor for numerous biochemical processes including carbohydrate and amino acid metabolism pathways and glucocorticoid receptor regulation.^17,18 However, a double-blinded, placebo-controlled RCT failed to show efficacy of once-daily pyridoxine hydrochloride 50 mg in improving erythema, itching, or nocturnal sleep disturbance associated with AD in a cohort of 48 children. The investigators concluded that pyridoxine supplementation cannot be recommended to improve the symptoms of AD in children.¹⁹

Zinc is an essential nutrient that functions as an important cofactor in cell metabolism and growth pathways.²⁰ One study showed that intracellular erythrocyte zinc levels were significantly lower in AD patients compared to healthy controls (P<.001); however, there was no observed difference in serum zinc levels (P=.148). Furthermore, greater disease severity as determined by the SCORing Atopic Dermatitis (SCORAD) index was negatively correlated with erythrocyte zinc levels (r=−0.791; P<.001).²¹ Kim et al²² investigated hair zinc levels and the efficacy of oral zinc supplementation in children with mild to moderate AD. Mean (SD) hair zinc levels were lower in the AD group compared to the control group (113.10 [33.6] μg vs 130.90 [36.63] μg [P=.012]). Of 41 AD patients with low zinc levels, 22 were allocated to group A, which received oral zinc oxide 12 mg for 8 weeks, and 19 were allocated to group B, which did not receive any supplementation over the same period. Groups A and B also received oral antihistamines and topical moisturizers. Mean (SD) zinc levels increased significantly in group A from 96.36 (21.05) μg to 131.81 (27.45) μg (P<.001). Furthermore, relative to group B, group A showed significantly greater improvements in eczema area and severity index (P=.044), transepidermal water loss (P=.015), and visual analog scale for pruritus (P<.001) at the end of 8 weeks. The authors concluded that oral zinc supplementation might be an effective adjunctive therapy for AD patients with low hair zinc levels.²²

Researchers also have explored the efficacy of fat-soluble vitamins D and E in treating AD. Vitamin D is thought to downregulate IgE-mediated skin reactions and decrease adverse effects of UV light on the skin.^23,24 A double-blind, placebo-controlled trial randomized 45 patients with AD to 4 groups: vitamins D and E placebos (n=11), 1600 IU vitamin D₃ plus vitamin E placebo (n=12), 600 IU vitamin E (synthetic all-rac-α-tocopherol) plus vitamin D placebo (n=11), and 1600 IU vitamin D₃ plus 600 IU vitamin E (synthetic all-rac-α-tocopherol)(n=11).²⁵ After 60 days, the SCORAD index was reduced by 28.9% in the placebo group, 34.8% in the vitamin D₃ group, 35.7% in the vitamin E group, and 64.3% in the combined vitamins D and E group (P=.004). Furthermore, prior to intervention, a negative correlation was demonstrated between plasma α-tocopherol concentration and the SCORAD index (r=−.33; P=.025).²⁵ Thus, supplementing vitamins D and E may play a beneficial role in the treatment of AD.

Other emerging studies are investigating the role of the gut microbiome in various pathologies. Prebiotics may alter the gut microbiome and are thought to play a role in reducing intestinal inflammation.²⁶ One randomized, placebo-controlled, parallel study examined the effect of prebiotic oligosaccharide supplementation on the development of AD in at-risk children, defined as having a biological parent with a history of asthma, allergic rhinitis, or AD.²⁷ At 6-month follow-up, 10 infants (9.8%)(95% CI, 5.4%-17.1%) in the intervention group (n=102) and 24 infants (23.1%)(95% CI, 16.0%-32.1%) in the placebo group (n=104) had developed AD. The authors postulated that the prebiotic oligosaccharides might play a role in immune modulation by altering bowel flora and preventing the development of AD in infancy.²⁷

Notably, a 2012 Cochrane review evaluated 11 studies of dietary supplements as possible treatment options for AD. The authors concluded that the evidence was minimal to support the regular use of dietary supplements, especially due to their high cost as well as the possibility that high levels of certain vitamins (eg, vitamin D) may cause long-term complications.²⁶

Psoriasis

Psoriasis is an autoimmune skin condition that has an annual prevalence ranging from approximately 1% to 9% in adults residing in Western countries.^28,29 Some have argued that due to decreased bacterial diversity and increased bacterial growth in the small bowel, psoriatic patients are exposed to higher levels of bacterial peptidoglycans and endotoxins.³⁰ To combat the absorption of these substances in psoriasis patients, we advocate for a vegetarian diet with low fats, limited alcohol consumption, and supplements of bile acids and bioflavonoid.

The effects of very long chain fatty acids also have been examined. A 4-month, double-blind, multicenter RCT compared the effects of daily supplementation with 6 g of either omega-3 fatty acids or omega-6 fatty acids in patients with mild to moderate plaque psoriasis.³¹ Psoriasis area and severity index scores and patient subjective scores did not change significantly in either group; however, scaling was reduced in both groups (P<.01). The group receiving omega-3 fatty acids had decreased cellular infiltration (P<.01), and the group receiving omega-6 fatty acids had decreased desquamation and redness (P<.05). In the omega-6 group, there was a significant correlation between clinical improvement (decrease in clinical score) and increase in serum eicosapentaenoic acid (r=−0.34; P<.05) and total omega-3 fatty acids (r=−0.36; P<.05). Overall, the authors concluded that supplementation with omega-3 fatty acids (fish oil) was no better than omega-6 fatty acids (corn oil) for treatment of psoriasis.³¹

Some dermatologists have advocated for the use of oral vitamin D supplementation as an adjunctive treatment of psoriasis, given that it is inexpensive and also may play a role in reducing the risk for cancer and cardiovascular events.³² One study evaluated the level of 25-hydroxy vitamin D in 43 psoriasis patients compared to 43 healthy controls. Mean (SD) vitamin D levels were significantly lower in psoriasis patients (13.3 [6.9]) compared to controls (22.4 [18.4])(P=.004).³³ A cross-sectional study similarly found significantly higher rates of vitamin D deficiency (25-hydroxy vitamin D <20 ng/mL) in psoriatic patients (57.8%) compared to patients with rheumatoid arthritis (37.5%) and healthy controls (29.7%)(P<.001). Interestingly, during winter the prevalence of vitamin D deficiency increased to 80.9%, 41.3%, and 30.3% in the 3 groups, respectively; however, no significant correlation was seen between psoriasis severity, as measured by psoriasis area and severity index, and serum vitamin D levels.³⁴ Although vitamin D deficiency may be more prevalent among patients with psoriasis, data regarding the efficacy of treating psoriasis with oral vitamin D supplementation is still lacking.

Conclusion

Our understanding of the link between diet and dermatologic conditions continues to evolve. Recent data for several dietary supplements and therapies showed promising results in repairing signs of photoaging, as well as treating AV, AD, and psoriasis. As patients seek these adjunctive therapies, it is important for physicians to be well informed on the benefits and risks to appropriately counsel patients.

Globally, physicians advocate for a low-glycemic diet rich in fruits and vegetables. Furthermore, the cosmetic diet can be enhanced by the consumption of dietary supplements such as beta-carotene, collagen peptides, zinc, and fat-soluble vitamins such as vitamins D and E. However, prospective RCTs are needed to further investigate the role of these dietary elements in treating and improving dermatologic conditions.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.

Acne vulgaris is prevalent in the general population, with 40 to 50 million affected individuals in the United States.¹ Severe inflammation and injury can lead to disfiguring scarring, which has a considerable impact on quality of life.² Numerous therapeutic options for acne scarring are available, including microneedling with and without platelet-rich plasma (PRP), lasers, chemical peels, and dermal fillers, with different modalities suited to individual patients and scar characteristics. This article reviews updates in treatment options for acne scarring.

Microneedling

Microneedling, also known as percutaneous collagen induction or collagen induction therapy, has been utilized for more than 2 decades.³ Dermatologic indications for microneedling include skin rejuvenation,^4-6 atrophic acne scarring,^7-9 and androgenic alopecia.^10,11 Microneedling also has been used to enhance skin penetration of topically applied drugs.^12-15 Fernandes¹⁶ described percutaneous collagen induction as the skin’s natural response to injury. Microneedling creates small wounds as fine needles puncture the epidermis and dermis, resulting in a cascade of growth factors that lead to tissue proliferation, regeneration, and a collagen remodeling phase that can last for several months.^8,16

Microneedling has gained popularity in the treatment of acne scarring.⁷ Alam et al⁹ conducted a split-face randomized clinical trial (RCT) to evaluate acne scarring after 3 microneedling sessions performed at 2-week intervals. Twenty participants with acne scarring on both sides of the face were enrolled in the study and one side of the face was randomized for treatment. Participants had at least two 5×5-cm areas of acne scarring graded as 2 (moderately atrophic scars) to 4 (hyperplastic or papular scars) on the quantitative Global Acne Scarring Classification system. A roller device with a 1.0-mm depth was used on participants with fine, less sebaceous skin and a 2.0-mm device for all others. Two blinded investigators assessed acne scars at baseline and at 3 and 6 months after treatment. Scar improvement was measured using the quantitative Goodman and Baron scale, which provides a score according to type and number of scars.¹⁷ Mean scar scores were significantly reduced at 6 months compared to baseline on the treatment side (P=.03) but not the control side. Participants experienced minimal pain associated with microneedling therapy, rated 1.08 of 10, and adverse effects were limited to mild transient erythema and edema.⁹ Several other clinical trials have demonstrated clinical improvements with microneedling.^18-20

The benefits of microneedling also have been observed on a histologic level. One group of investigators explored the effects of microneedling on dermal collagen in the treatment of various atrophic acne scars in 10 participants.⁷ After 6 treatment sessions performed at 2-week intervals, dermal collagen was assessed via punch biopsy. A roller device with a needle depth of 1.5 mm was used for all patients. At 1 month after treatment compared to baseline, mean (SD) levels of type I collagen were significantly increased (67.1% [4.2%] vs 70.4% [5.4%]; P=.01) as well as at 3 months after treatment compared to baseline for type III collagen (61.4% [3.6%] vs 74.3% [7.4%]; P=.01), type VII collagen (15.2% [2.1%] vs 21.3% [1.2%]; P=.03), and newly synthesized collagen (14.5% [5.8%] vs 19.5% [3.2%]; P=.02). Total elastin levels were significantly decreased at 3 months after treatment compared to baseline (51.3% [6.7%] vs 46.9% [4.3%]; P=.04). Adverse effects were limited to transient erythema and edema.⁷

Microneedling With Platelet-Rich Plasma

Microneedling has been combined with platelet-rich plasma (PRP) in the treatment of atrophic acne scars.²¹ In addition to inducing new collagen synthesis, microneedling aids in the absorption of PRP, an autologous concentrate of platelets that is obtained through peripheral venipuncture. The concentrate is centrifuged into 3 layers: (1) platelet-poor plasma, (2) PRP, and (3) erythrocytes.²² Platelet-rich plasma contains growth factors such as platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor, as well as cell adhesion molecules.^22,23 The application of PRP is thought to result in upregulated protein synthesis, greater collagen remodeling, and accelerated wound healing.²¹

Several studies have shown that the addition of PRP to microneedling can improve treatment outcome (Table 1).^24-27 Severity of acne scarring can be improved, such as reduced scar depth, by using both modalities synergistically (Figure).²⁴ Asif et al²⁶ compared microneedling with PRP to microneedling with distilled water in the treatment of 50 patients with atrophic acne scars graded 2 to 4 (mild to severe acne scarring) on the Goodman’s Qualitative classification and equal Goodman’s Qualitative and Quantitative scores on both halves of the face.^17,28 The right side of the face was treated with a 1.5-mm microneedling roller with intradermal and topical PRP, while the left side was treated with distilled water (placebo) delivered intradermally. Patients underwent 3 treatment sessions at 1-month intervals. The area treated with microneedling and PRP showed a 62.20% improvement from baseline after 3 treatments, while the placebo-treated area showed a 45.84% improvement on the Goodman and Baron quantitative scale.²⁶

Chawla²⁵ compared microneedling with topical PRP to microneedling with topical vitamin C in a split-face study of 30 participants with atrophic acne scarring graded 2 to 4 on the Goodman and Baron scale. A 1.5-mm roller device was used. Patients underwent 4 treatment sessions at 1-month intervals, and treatment efficacy was evaluated using the qualitative Goodman and Baron scale.²⁸ Participants experienced positive outcomes overall with both treatments. Notably, 18.5% (5/27) on the microneedling with PRP side demonstrated excellent response compared to 7.4% (2/27) on the microneedling with vitamin C side.²⁵

Laser Treatment

Laser skin resurfacing has shown to be efficacious in the treatment of both acne vulgaris and acne scarring. Various lasers have been utilized, including nonfractional CO₂ and erbium-doped:YAG (Er:YAG) lasers, as well as ablative fractional lasers (AFLs) and nonablative fractional lasers (NAFLs).²⁹

One retrospective study of 58 patients compared the use of 2 resurfacing lasers—10,600-nm nonfractional CO₂ and 2940-nm Er:YAG—and 2 fractional lasers—1550-nm NAFL and 10,600-nm AFL—in the treatment of atrophic acne scars.²⁹ A retrospective photographic analysis was performed by 6 blinded dermatologists to evaluate clinical improvement on a scale of 0 (no improvement) to 10 (excellent improvement). The mean improvement scores of the CO₂, Er:YAG, AFL, and NAFL groups were 6.0, 5.8, 2.2, and 5.2, respectively, and the mean number of treatments was 1.6, 1.1, 4.0, and 3.4, respectively. Thus, patients in the fractional laser groups required more treatments; however, those in the resurfacing laser groups had longer recovery times, pain, erythema, and postinflammatory hyperpigmentation. The investigators concluded that 3 consecutive AFL treatments could be as effective as a single resurfacing treatment with lower risk for complications.²⁹

A split-face RCT compared the use of the fractional Er:YAG laser on one side of the face to microneedling with a 2.0-mm needle on the other side for treatment of atrophic acne scars.³⁰ Thirty patients underwent 5 treatments at 1-month intervals. At 3-month follow-up, the areas treated with the Er:YAG laser showed 70% improvement from baseline compared to 30% improvement in the areas treated with microneedling (P<.001). Histologically, the Er:YAG laser showed a higher increase in dermal collagen than microneedling (P<.001). Furthermore, the Er:YAG laser yielded significantly lower pain scores (P<.001); however, patients reported higher rates of erythema, swelling, superficial crusting, and total downtime.³⁰

Lasers With PRP
More recent studies have examined the use of laser therapy in addition to PRP for the treatment of acne scars (Table 2).^31-34 Abdel Aal et al³³ examined the use of the ablative fractional CO₂ laser with and without intradermal PRP in a split-face study of 30 participants with various types of acne scarring (ie, boxcar, ice pick, and rolling scars). Participants underwent 2 treatments at 4-week intervals. Evaluations were performed by 2 blinded dermatologists 6 months after the final laser treatment using the qualitative Goodman and Baron scale.²⁸ Both treatments yielded improvement in scarring, but the PRP-treated side showed shorter durations of postprocedure erythema (P=.0052) as well as higher patient satisfaction scores (P<.001) than laser therapy alone.³³

In another split-face study, Gawdat et al³² examined combination treatment with the ablative fractional CO₂ laser and PRP in 30 participants with atrophic acne scars graded 2 to 4 on the qualitative Goodman and Baron scale.²⁸ Participants were randomized to 2 different treatment groups: In group 1, half of the face was treated with the fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and intradermal saline. In group 2, half of the face was treated with fractional CO₂ laser and intradermal PRP, while the other half was treated with fractional CO₂ laser and topical PRP. All patients underwent 3 treatment sessions at 1-month intervals with assessment occurring a 6-month follow-up using the qualitative Goodman and Baron Scale.²⁸ In all participants, areas treated with the combined laser and PRP showed significant improvement in scarring (P=.03) and reduced recovery time (P=.02) compared to areas treated with laser therapy only. Patients receiving intradermal or topical PRP showed no statistically significant differences in improvement of scarring or recovery time; however, areas treated with topical PRP had significantly lower pain levels (P=.005).³²

Lee et al³¹ conducted a split-face study of 14 patients with moderate to severe acne scarring treated with an ablative fractional CO₂ laser followed by intradermal PRP or intradermal normal saline injections. Patients underwent 2 treatment sessions at 4-week intervals. Photographs taken at baseline and 4 months posttreatment were evaluated by 2 blinded dermatologists for clinical improvement using a quartile grading system. Erythema was assessed using a skin color measuring device. A blinded dermatologist assessed patients for adverse events. At 4-month follow-up, mean (SD) clinical improvement on the side receiving intradermal PRP was significantly better than the control side (2.7 [0.7] vs 2.3 [0.5]; P=.03). Erythema on posttreatment day 4 was significantly less on the side treated with PRP (P=.01). No adverse events were reported.³¹

Another split-face study compared the use of intradermal PRP to intradermal normal saline following fractional CO₂ laser treatment.³⁴ Twenty-five participants with moderate to severe acne scars completed 2 treatment sessions at 4-week intervals. Additionally, skin biopsies were collected to evaluate collagen production using immunohistochemistry, quantitative polymerase chain reaction, and western blot techniques. Experimental fibroblasts and keratinocytes were isolated and cultured. The cultures were irradiated with a fractional CO₂ laser and treated with PRP or platelet-poor plasma. Cultures were evaluated at 30 minutes, 24 hours, and 48 hours. Participants reported 75% improvement of acne scarring from baseline in the side treated with PRP compared to 50% improvement of acne scarring from baseline in the control group (P<.001). On days 7 and 84, participants reported greater improvement on the side treated with PRP (P=.03 and P=.02, respectively). On day 28, skin biopsy evaluation yielded higher levels of TGF-β1 (P=.02), TGF-β3 (P=.004), c-myc (P=.004), type I collagen (P=.03), and type III collagen (P=.03) on the PRP-treated side compared to the control side. Transforming growth factor β increases collagen and fibroblast production, while c-myc leads to cell cycle progression.^35-37 Similarly, TGF-β1, TGF-β3, types I andIII collagen, and p-Akt were increased in all cultures treated with PRP and platelet-poor plasma in a dose-dependent manner.³⁴ p-Akt is thought to regulate wound healing³⁸; however, PRP-treated keratinocytes yielded increased epidermal growth factor receptor and decreased keratin-16 at 48 hours, which suggests PRP plays a role in increasing epithelization and reducing laser-induced keratinocyte damage.³⁹ Adverse effects (eg, erythema, edema, oozing) were less frequent in the PRP-treated side.³⁴

Chemical Peels

Chemical peels are widely used in the treatment of acne scarring.⁴⁰ Peels improve scarring through destruction of the epidermal and/or dermal layers, leading to skin exfoliation, rejuvenation, and remodeling. Superficial peeling agents, which extend to the dermoepidermal junction, include resorcinol, tretinoin, glycolic acid, lactic acid, salicylic acid, and trichloroacetic acid (TCA) 10% to 35%.⁴¹ Medium-depth peeling agents extend to the upper reticular dermis and include phenol, TCA 35% to 50%, and Jessner solution (resorcinol, lactic acid, and salicylic acid in ethanol) followed by TCA 35%.⁴¹ Finally, the effects of deep peeling agents reach the mid reticular dermis and include the Baker-Gordon or Litton phenol formulas.⁴¹ Deep peels are associated with higher rates of adverse outcomes including infection, dyschromia, and scarring.^41,42

An RCT was performed to evaluate the use of a deep phenol 60% peel compared to microneedling with a 1.5-mm roller device plus a TCA 20% peel in the treatment of atrophic acne scars.⁴³ Twenty-four patients were randomly and evenly assigned to both treatment groups. The phenol group underwent a single treatment session, while the microneedling plus TCA group underwent 4 treatment sessions at 6-week intervals. Both groups were instructed to use daily topical tretinoin and hydroquinone 2% in the 2 weeks prior to treatment. Posttreatment results were evaluated using a quartile grading scale. Scarring improved from baseline by 75.12% (P<.001) in the phenol group and 69.43% (P<.001) in the microneedling plus TCA group, with no significant difference between groups. Adverse effects in the phenol group included erythema and hyperpigmentation, while adverse events in the microneedling plus TCA group included transient pain, edema, erythema, and desquamation.⁴³

Another study compared the use of a TCA 15% peel with microneedling to PRP with microneedling and microneedling alone in the treatment of atrophic acne scars.⁴⁴ Twenty-four patients were randomly assigned to the 3 treatment groups (8 to each group) and underwent 6 treatment sessions with 2-week intervals. A roller device with a 1.5-mm needle was used for microneedling. Microneedling plus TCA and microneedling plus PRP were significantly more effective than microneedling alone (P=.011 and P=.015, respectively); however, the TCA 15% peel with microneedling resulted in the largest increase in epidermal thickening. The investigators concluded that combined use of a TCA 15% peel and microneedling was the most effective in treating atrophic acne scarring.⁴⁴

Dermal Fillers

Dermal or subcutaneous fillers are used to increase volume in depressed scars and stimulate the skin’s natural production.⁴⁵ Tissue augmentation methods commonly are used for larger rolling acne scars. Options for filler materials include autologous fat, bovine, or human collagen derivatives; hyaluronic acid; and polymethyl methacrylate microspheres with collagen.⁴⁵ Newer fillers are formulated with lidocaine to decrease pain associated with the procedure.⁴⁶ Hyaluronic acid fillers provide natural volume correction and have limited potential to elicit an immune response due to their derivation from bacterial fermentation. Fillers using polymethyl methacrylate microspheres with collagen are permanent and effective, which may lead to reduced patient costs; however, they often are not a first choice for treatment.^45,46 Furthermore, if dermal fillers consist of bovine collagen, it is necessary to perform skin testing for allergy prior to use. Autologous fat transfer also has become popular for treatment of acne scarring, especially because there is no risk of allergic reaction, as the patient’s own fat is used for correction.⁴⁶ However, this method requires a high degree of skill, and results are unpredictable, generally lasting from 6 months to several years.

Therapies on the horizon include autologous cell therapy. A multicenter, double-blinded, placebo-controlled RCT examined the use of an autologous fibroblast filler in the treatment of bilateral, depressed, and distensible acne scars that were graded as moderate to severe.⁴⁷ Autologous fat fibroblasts were harvested from full-thickness postauricular punch biopsies. In this split-face study, 99 participants were treated with an intradermal autologous fibroblast filler on one cheek and a protein-free cell-culture medium on the contralateral cheek. Participants received an average of 5.9 mL of both autologous fat fibroblasts and cell-culture medium over 3 treatment sessions at 2-week intervals. The autologous fat fibroblasts were associated with greater improvement compared to cell-culture medium based on participant (43% vs 18%), evaluator (59% vs 42%), and independent photographic viewer’s assessment.⁴⁷

Conclusion

Acne scarring is a burden affecting millions of Americans. It often has a negative impact on quality of life and can lead to low self-esteem in patients. Numerous trials have indicated that microneedling is beneficial in the treatment of acne scarring, and emerging evidence indicates that the addition of PRP provides measurable benefits. Similarly, the addition of PRP to laser therapy may reduce recovery time as well as the commonly associated adverse events of erythema and pain. Chemical peels provide the advantage of being easily and efficiently performed in the office setting. Finally, the wide range of available dermal fillers can be tailored to treat specific types of acne scars. Autologous dermal fillers recently have been used and show promising benefits. It is important to consider desired outcome, cost, and adverse events when discussing therapeutic options for acne scarring with patients. The numerous therapeutic options warrant further research and well-designed RCTs to ensure optimal patient outcomes.