REVIEW

Nutraceuticals: A Review

Skylar A. Souyoul . Katharine P. Saussy . Mary P. Lupo

Received: October 16, 2017 / Published online: February 6, 2018� The Author(s) 2018. This article is an open access publication

ABSTRACT

Skin aging is continuously influenced by vari-ous internal and external factors such as thebiologic progression of cells, ultraviolet (UV)radiation, tobacco, nutritional deficiencies, andhormonal imbalances that lead to the degrada-tion of skin cells. Through the degradation ofskin cells, free radicals and inflammationweaken repair mechanisms and result in colla-gen and elastic fiber breakdown. The appear-ance of aging skin is highlighted by skinroughness, wrinkling, pigmentation change,telangiectasias, loss of elasticity, and decreasedfirmness, all of which are accelerated by theseinternal and external factors. Throughout theyears, nutraceuticals have been studied to delayand fight against these internal and externalfactors, many of which are found in foods andbyproducts consumed naturally. The aim of thisreview is to aid dermatologists in understandingthe mechanism of action of popular

nutraceuticals and their possible efficacy inantiaging and skin health.

Keywords: b-Carotene; Fatty acids; Lutein;Lycopene; Minerals; Nutraceuticals;Polyphenols; Vitamin C; Vitamin E; Zeaxanthin

INTRODUCTION

The skin is the largest organ of the human bodyand is perpetually aging by both internal andexternal factors [1]. The internal factors are apart of the natural aging process within cells,but can be accelerated by external factors suchas ultraviolet (UV) radiation, tobacco, inade-quate nutrition, and hormonal imbalances.These external factors cause the production offree radicals and inflammation that fragmentand degrade collagen and elastic fibers [2]. Overtime, both these internal and external influ-ences lead to increased skin roughness, wrin-kling, pigmentation change, telangiectasias,loss of elasticity, and decreased firmness, givingskin its aged appearance [2, 3].

Nutraceuticals are oral dietary componentsnaturally found in foods and believed to have amedical or health benefit [4]. Dr. StephenDefelice, who combined the words ‘‘nutrition’’and ‘‘pharmaceutical,’’ coined the term in 1989.Here, the theoretical action and clinical benefitof some dermatologic nutraceuticals are

Enhanced content To view enhanced content for thisarticle go to http://www.medengine.com/Redeem/276299605B0947D5.

S. A. Souyoul (&) � M. P. LupoLupo Center for Aesthetic and GeneralDermatology, New Orleans, LA, USAe-mail: drsouyoul@drmarylupo.com

K. P. SaussyDepartment of Internal Medicine, TulaneUniversity, New Orleans, LA, USA

Dermatol Ther (Heidelb) (2018) 8:5–16

https://doi.org/10.1007/s13555-018-0221-x

reviewed. The aim of this review is to aid der-matologists in understanding the mechanism ofaction of popular nutraceuticals and their pos-sible efficacy in antiaging and skin health. Thisarticle is based on previously conducted studiesand does not involve any new studies of humanor animal subjects performed by any of theauthors.

AMINO ACIDS

N-Acetylcysteine

N-Acetylcysteine is the prodrug form of L-cys-teine and has both oral and topical bioavail-ability [5, 6]. N-Acetylcysteine gives rise toglutathione, which is the most abundantendogenous intracellular antioxidant and playsa pivotal role in the body’s antioxidant defense[6, 7]. The rate of glutathione synthesis decrea-ses as humans’ age, leading to glutathionedeficiency, which leaves the body susceptible tooxidative stress [7]. Increased oxidative stressleads to increased DNA damage and aging [7].

A study by Sekhar et al. [7] found that elderlysubjects had significantly lower intracellularglutathione synthesis and concentrations whencompared to younger subjects. After 2 weeks ofcysteine and glycine supplementation, elderlysubjects had a significant increase in their redblood cell glycine, cysteine, and glutathioneconcentrations [7]. In addition, after supple-mentation, there was a decline in both oxida-tive stress and plasma markers for oxidantdamage [7]. The Food and Nutrition Board ofthe Institute of Medicine’s recommended diet-ary allowance (RDA) of N-acetylcysteine has notbeen established. Further clinical studies areneeded to determine ideal daily consumption ofN-acetylcysteine to achieve maximal skinbenefit.

CAROTENOIDS

Carotenoids are a family of over 600 fat-solubleplant pigments, approximately 20 of which arepresent in human tissues and blood [3, 8]. Theyare potent reactive oxygen species (ROS)

scavengers, protecting the skin from oxidativestress [8]. Humans and animals cannot synthe-size carotenoids, so they must obtain them viaingestion of foods or supplements [8]. Skinconcentrations of carotenoids increase withingestion of the components, but decrease withoxidative stress and UV exposure [3]. Here, wefocus on four of the major dietary carotenoids:b-carotene, lycopene, lutein, and zeaxanthin.

b-Carotene

b-Carotene is a precursor to vitamin A. It pro-tects cells from damage by inhibiting free radi-cal and singlet oxygen-induced lipidperoxidation [3]. It also has photoprotectiveproperties, which increase the minimal ery-thema dose (MED), and protects against sun-burn development and photosuppression of theimmune system [3, 8, 9]. In mice, b-carotenehas been shown to prevent wrinkle formationand decrease matrix metalloproteinase (MMP)-9activity, protecting the extracellular matrix(ECM) from degradation [3].

Foods rich in b-carotene are green leafy veg-etables, orange root vegetables, and yellow ororange fruits [3]. b-Carotene is a precursor tovitamin A; thus, the RDA is determined throughconsumption of vitamin A. The Food andNutrition Board of the Institute of Medicine’sRDA of vitamin A is 900 lg retinol activityequivalency (RAE) a day for men and 700 lgRAE a day for women ages 19 years and older[10]. According to the Institute of Medicine’sInterconversion of Vitamin A and CarotenoidUnits Table, 2 lg of supplemental all-trans-b-carotene is equal to 1 RAE and 12 lg of dietaryall-trans-b-carotene is equal to 1 RAE. Thus, theRDA of supplemental all-trans-b-carotene is1800 lg a day for men and 1400 lg a day forwomen, and the RDA for dietary all-trans-b-carotene is 10,800 lg a day for men and 8400 lga day for women [10]. Long-term b-carotenesupplementation has been associated with anincreased risk of lung cancer, so further studiesare needed to determine the optimal dailyallowance while accessing for supplementationhealth risks [9].

6 Dermatol Ther (Heidelb) (2018) 8:5–16

Lutein and Zeaxanthin

Lutein and zeaxanthin are the two primaryxanthophyll carotenoids in the retina and aregenerally thought to promote eye health; how-ever, significant amounts of both are found inhuman skin [11]. In both the skin and eyes,these carotenoids work as a filler to blockdamaging blue wavelengths and as antioxidantsto prevent free radical damage [11, 12].

Juturu et al. [12] evaluated a daily oral sup-plement containing 10 mg of lutein and 2 mg ofzeaxanthin isomers. They concluded thatwithin 12 weeks, the supplement increased themean MED and significantly improved skintone, luminance, and color [12]. Other studieshave shown that lutein and zeaxanthin protectkeratinocytes from UV radiation-induced pho-toaging, stop ECM degradation by inhibitingMMPs, and decrease lipid peroxidation in theskin [11, 13]. These skin effects can be seen withlutein and zeaxanthin oral supplementation,topical application, or both simultaneously forenhanced benefit [11, 13].

Humans are unable to produce lutein orzeaxanthin, so they must be obtained exoge-nously [10]. Both are found in highest concen-tration in green leafy vegetables, but are foundin a more bioavailable form in eggs [13]. TheFood and Nutrition Board of the Institute ofMedicine’s RDA of lutein and zeaxanthin hasnot been established; however, between6–10 mg a day of lutein and 2 mg a day ofzeaxanthin has been recommended in previousstudies [10, 12, 14]. Of note, the AmericanOptometric Association recommends taking10 mg a day of lutein and 2 mg a day of zeax-anthin if one is not getting adequate amountsthrough diet alone to potentially reduce the riskof age-related macular degeneration and catar-acts [15].

Lycopene

Lycopene has no vitamin A activity, but isconsidered the best singlet oxygen quencher inthe carotenoid family [3]. Studies have shownthat consumption of tomato paste, which ishigh in lycopene, significantly lowers UV-

induced erythema and decreases MMP-1 activ-ity, an enzyme involved in the breakdown ofcollagen [16]. In vitro studies of lycopene haveshown its ability to inhibit proliferation of sev-eral types of cancer cells via cell-cycle arrest andinduction of apoptosis [3]. There is also a sig-nificant correlation between higher skin con-centrations of lycopene and a decrease in skinroughness [3].

Foods rich in lycopene are tomatoes, pinkgrapefruit, and watermelon [10]. The Food andNutrition Board of the Institute of Medicine hasnot established an RDA for lycopene, so furtherstudies are needed to determine the optimaldaily allowance while accessing for supple-mentation health risks.

FATTY ACIDS

a-Linolenic Acid, Eicosapentaenoic Acid,and Docosahexaenoic Acid

Essential fatty acids make up long-chainpolyunsaturated fatty acids that can be dividedinto two groups, omega-3 and omega-6 [17].Omega-3 fatty acids originate from linolenicacid, whereas omega-6 fatty acids originatefrom linoleic acid (LA) [17]. The three mostcommon omega-3 essential fatty acids arealpha-linolenic acid (ALA), eicosapentaenoicacid (EPA), and docosahexaenoic acid (DHA)[17]. These three fatty acids lie on a metabolicspectrum with ALA serving as the precursor andEPA and DHA serving as ALA’s metabolizedproducts [18].

In the stratum corneum a combination oflipids serves as a protective barrier to the skinsurface and cellular structure [19]. LA has thehighest fatty acid concentration within theepidermis and serves as an important structuralcomponent [20], while omega-3 polyunsatu-rated fatty acids play an important anti-in-flammatory role [20, 21]. Polyunsaturated fattyacids such ALA, EPA, and DHA hinder the for-mation of pro-inflammatory cytokines such asprostaglandins, leukotrienes, tumor necrosisfactor-a, interferon-c, and interleukins-12 and-6 [20, 21]. Studies have reported a significantreduction in UV-radiation-induced

Dermatol Ther (Heidelb) (2018) 8:5–16 7

inflammation when taking fatty acid supple-ments, attributed to the potential decrease inprostaglandin-E2 levels during the inflamma-tory response [17–19]. Another study reportedan increase in the MED in study participantswho took 4 g of EPA daily [20].

In 2017, Wang et al. demonstrated a way toquantify the skin’s fatty acid concentration andcomposition using gas chromatography. Thestudy resulted in a statistically significantincrease in the concentration of EPA and DHAin the skin of mice within 2 weeks of initiating adiet supplemented with fish oil [18]. Four weeksafter of initiating the supplemented diet, thisincrease plateaued [18].

Essential fatty acids must be consumedthrough diet or supplementation since humansdo not have the enzymes to produce them denovo, leading to a variation in the fatty acidmake up within the skin [18, 20]. Omega-3 fattyacids, as well as omega-6 fatty acids, are foundprimarily in oils such as flaxseed oil, canola oil,hemp seed oil, and other foods including cold-water fish, such as salmon and trout, nuts, andseeds [17, 20]. The Food and Nutrition Board ofthe Institute of Medicine does not have an RDAfor any of the fatty acids mentioned abovebecause of a lack of evidence, but does have anadequate intake (AI), which is determined bythe largest median intake where deficiency isextremely rare [22]. The AI for LA is 17 g per dayfor men and 12 g per day for women ages 19–50,and 14 and 11 g per day for men and womenage 51 and above [22]. The AI for ALA is 1.6 gper day for men and 1.1 g per day for womenages 19 and older [22]. Additional studies areneeded to determine the ideal daily dose ofessential fatty acids to achieve maximal skinbenefit.

MINERALS

Copper

Copper is a trace mineral found naturally in soilwith many innate properties. Copper serves asan important cofactor in enzymatic reactionsduring collagen crosslinking with lysyl oxidaseand skin pigmentation with tyrosinase [23, 24].

Copper promotes keratinocyte and fibroblastproliferation leading to skin rejuvenation andwound repair through its collagen crosslinkingproperties [25]. Lastly, copper has been used intopical treatments for wound healing to pro-mote repair of damaged skin because of its anti-inflammatory and anti-bacterial effects [25].

Dietary copper is found in highest concen-tration in nuts, seeds, seafood, meat, and grains[10]. Human deficiencies are rare and are mostcommonly seen in people with intestinal mal-absorption [10]. The Food and Nutrition Boardof the Institute of Medicine’s recommendeddietary allowance of copper is 900 lg a day formen and women ages 19 and older [10]. Addi-tional studies are needed to determine the idealdaily dose of copper to achieve maximal skinbenefit.

Selenium

Selenium is a trace element, also referred to asan essential mineral, found in soil, water, andspecific foods. It exists in multiple forms, butpredominantly found in humans as selenome-thionine [26]. It plays an important role in DNAsynthesis and repair, cell apoptosis, and guard-ing against oxidative damage [26]. Seleniumworks through glutathione peroxidases andthioredoxin reductases, which remove damag-ing lipid hydroperoxides, hydrogen peroxide,and peroxynitrite formed during oxidativestress, leading to cell membrane stabilizationand defense against DNA damage [27, 28].

Selenium, in multiple forms, is found inhighest concentration in animal proteins suchas meat and seafood, the majority of which arehighly bioavailable [29]. The precise concen-tration of selenium is dependent on the sele-nium concentration within the soil where thoseanimals and plants were produced, which variesbetween land sources [29]. The Food andNutrition Board of the Institute of Medicine’sRDA of selenium is 55 lg a day for men andwomen ages 19 years and older [29]. Additionalstudies are needed to determine the ideal dailydose of selenium to achieve maximal skinbenefit.

8 Dermatol Ther (Heidelb) (2018) 8:5–16

Zinc

Zinc is an essential mineral found naturally inwhole grains, red meat, seafood, and fortified inproducts such as cereal [10]. Zinc is an impor-tant cofactor for cellular activity and defense. Itprotects against lipid peroxidation, UV-inducedcytotoxicity, and oxidative stress induced byROS made and distributed within the cytosol bymacrophages [27, 28].

The majority of the skin’s zinc stores arefound in the epidermis, where it is a necessaryelement for epidermal proliferation and ker-atinocyte differentiation [30]. Zinc plays amajor role in wound healing and keratinocytecell survival [30]. It is also anti-inflammatory byhindering intercellular adhesion molecule 1, apro-inflammatory marker of keratinocytes, anddecreasing the production of nitric oxide [30].

In 2001, it was estimated that 10% of the USpopulation consumes less than 50% of the rec-ommend daily allowance of zinc [31]. Thebioavailability of zinc is mainly dependent onzinc’s absorption and reabsorption propertiesfound within the human intestines [10]. Vary-ing concentrations of elements such as iron,copper, calcium, phosphate, and folate influ-ence the bioavailability of zinc in the body [10].Zinc is found in highest dietary concentrationsin foods such as non-milled whole grains, redmeats, and seafood [10]. The Food and Nutri-tion Board of the Institute of Medicine’s RDA ofzinc is 11 mg a day for men and 8 mg a day forwomen ages 19 years and older [10]. Additionalstudies are needed to determine the ideal dailydose of zinc to achieve maximal skin benefit.

POLYPHENOLS

Polyphenols are secondary metabolites of plantsand are found predominately in fruits, vegeta-bles, cereals, and beverages [32]. For years,polyphenols have been of interest for theirantimutagenic, anticarcinogenic, anti-inflam-matory, and antioxidant properties [28, 33].Extensive research has shown that throughthese properties different polyphenols can beprotective against numerous health concernsincluding cancer, hypertension, asthma,

diabetes, cardiovascular disease, and infection[32]. Over eight thousand different polyphenolcompounds have been identified, but here onlytwo will be discussed: curcumin and epigallo-catechin gallate (EGCG) [32].

Curcumin

Curcumin is a polyphenol derived from theturmeric spice. It has a yellow pigment, which isresponsible for the characteristic yellow color ofcurry [34]. Curcumin serves many biologicallyactive roles, as does EGCG, including the alikeanticarcinogenic, anti-inflammatory, andantioxidant roles [33].

Similarity to EGCG, curcumin has been sug-gested as a potential treatment for cancerbecause of its ability to hinder the production ofcancer cells and encourage apoptosis [35]. It hasbeen shown to promote cell death by influenc-ing the expression of p53 and decreasing theproduction of nuclear factor kappa B [33].

Curcumin’s anti-inflammatory properties areexhibited through its ability to suppress pro-inflammatory cytokines including chemokines,cyclooxygenase-2, prostaglandin E2, MMPs,interleukins (IL) such as IL-6 and IL-12, andtumor necrosis factor-a [34, 35]. In addition,curcumin serves as an antioxidant by suppress-ing ROS production, scavenging free oxygenradicals, and inhibiting lipid peroxidation[34, 35].

In 2017, Shailaja et al. studied curcumin’santi-inflammatory properties in albino rats as apotential anti-aging nutraceutical. The studycompared three dosages of oral daily curcuminsupplementation against two different standardrat feed and water diets. They report a statisti-cally significant decrease in the C-reactive pro-tein levels in the curcumin-supplementedgroup compared with the two control groups[36].

The Food and Nutrition Board of the Insti-tute of Medicine’s RDA of curcumin has notbeen established; however, the United StatesFood and Drug Administration (FDA) haslabeled curcumin safe for ingestion and phar-macologic use [35]. In 2016, Pal et al. [33]reported two studies of safe oral

Dermatol Ther (Heidelb) (2018) 8:5–16 9

supplementation of curcumin between 2–8 gper kg daily. Further studies are needed todetermine the optimal daily allowance whileaccessing for supplementation health risks.

Epigallocatechin Gallate (Egcg)

Tea polyphenols inhibit lipid peroxidation,limit the amount of UV radiation-induced DNAdamage, and reduce the amount ROS and freeradicals produced in the skin [28, 34]. EGCG isthe most potent tea polyphenol and is com-monly found in green tea [17, 28]. EGCG hasanti-inflammatory effects via the suppression ofpro-inflammatory inducers such as cyclooxyge-nase-2, MMPs, tumor necrosis factor-a, and IL-6, 8, and 12 [33]. Studies have also shown thatEGCG can diminish melanoma cell growth inhumans by supporting cell cycle arrest andapoptosis [33].

Health benefits of EGCG have been shownwith both topical application and ingestion,although some benefits are only seen with onedelivery method and not the other. In mice,studies have shown diminished radiation-in-duced effects with topical application. Theseeffects include deceased edema and erythema,preservation of skin antioxidant stores, andreduction of UV-induced skin tumors [3, 17].

Green tea has been reported to consist of themost polyphenol antioxidants, and the highestconcentration of EGCG is found within greentea leaves [17]. It is commercially available as awhite powder for oral consumption [17]. TheFood and Nutrition Board of the Institute ofMedicine’s RDA of EGCG has not been estab-lished. In 2017, Yates et al. completed anextensive literature search evaluating the toxi-city level of EGCG in daily human consump-tion. The results were inconclusive and needfuture investigation; however, publications byFrance and Italy report a proposed upper limitof approximately 300 mg per day of EGCG [37].Pal et al. report a phase I clinical study with200–1200 mg of daily consumption being welltolerated [33]. Further studies are needed todetermine the optimal daily allowance whileaccessing for supplementation health risks.

VITAMINS

Vitamin C

Vitamin C is a water-soluble compound. Bodilyconcentrations are maintained through con-sumption of vitamin C, as humans cannotsynthesize ascorbic acid de novo. Oxidation ofvitamin C produces dehydroxy ascorbic acid,which is shifted into our cells via glucosetransporters and then reduced back to ascorbicacid for cellular use [38]. Studies have shownthat oral vitamin C supplementation leads to anincrease in its plasma and skin content [39].

Vitamin C is a powerful antioxidant and freeradical scavenger that protects our tissues, cellmembranes, and DNA from oxidative damage.It also serves as an essential cofactor and elec-tron donor during collagen hydroxylation,encouraging the maturation of intracellular andextracellular collagen [26]. Vitamin C has beenshown to reduce UVB-induced oxidative dam-age and UV radiation-induced skin neoplasmsin mice and protect human keratinocytes fromUVA-induced lipid peroxidation [39, 40]. Vita-min C also decreases the malondialdehydecontent in the skin, which is a marker ofoxidative stress [39, 40].

Food sources containing the highest con-centrations of vitamin C are raw red and greenpeppers, oranges, grapefruits, kiwifruit, broc-coli, strawberries, and Brussels sprouts [41]. TheFood and Nutrition Board of the Institute ofMedicine’s RDA of vitamin C is 90 mg a day formen and 75 mg a day for women ages 19 yearsand older [29]. National surveys indicate thatmost adults and children in the US consumetheir RDA of vitamin C [41]. Additional studiesare needed to determine the ideal daily dose ofvitamin C to achieve maximal skin benefit.

Vitamin E

Vitamin E is a group of fat-soluble compounds.The most abundant and biologically active formof vitamin E, alpha-tocopherol (aT), is theleading form used in human metabolism [3, 42].aT protects the skin from UVB damage byhalting the formation of ROS, scavenging free

10 Dermatol Ther (Heidelb) (2018) 8:5–16

radicals, stabilizing the surface and membranesof cells, reducing the number of apoptotic cells,and minimizing the activation of nuclear factorkappa B [26, 43]. aT is also believed to be pho-toprotective as multiple studies have shownthat aT in combination with vitamin C sup-plementation increases the MED [3].

UV light reduces the skin’s concentration ofaT, promoting skin aging [3]. Luckily, the skin’sconcentration of aT can be increased with oralor topical delivery [3]. Naturally occurring oralsources of vitamin E are found in highest con-centrations in plant seeds such as sunflowerseeds, peanuts, almonds, walnuts, pecans, pis-tachios, and sesame seeds and in lesser amountsin fruits and vegetables [44, 45]. The Food andNutrition Board of the Institute of Medicine’sRDA of vitamin E is 15 mg a day for men andwomen ages 19 years and older [29]. Nationalsurveys have found that most Americans con-sume less than their RDA of vitamin E [46].However, these intake estimates might be lowbecause they did not account for the fats addedwhile cooking [46]. No adverse effects havebeen reported from consuming vitamin E infood; however, hemorrhage and altered bloodcoagulation were reported in animals whoconsumed supplements containing high dosesof aT [46]. Additional studies are needed todetermine the ideal daily allowance of vitaminE to achieve maximal skin benefit.

POTENTIAL FUTURENUTRACEUTICALS

Aloe Sterol

Collagen and elastin are the two main fibers inthe dermis and together makeup and maintainthe majority of the skin’s structure [47]. Degra-dation of these fibers, which is seen in chrono-logically aged skin, leads to a decrease incutaneous elasticity and an increase in cutaneousfragility [47]. Oral Aloe sterols have been shownto encourage the formation of type I and type IIIcollagen in human dermal fibroblasts, leading toincreased collagen production and improvedskin elasticity [48]. They have also been found todecrease the expression of MMP-2 and MMP-9,

protecting collagen and the ECM from degrada-tion, in UVB-irradiated hairless mice [47]. Inaddition, studies have showed that oral Aloesterol may encourage the production of hya-luronic acid in human dermal fibroblasts [49].Further studies are needed to determine the roleof oral Aloe sterols and optimal daily allowancewhile accessing for supplementationhealth risks.

Serenoa Repens

Serenoa repens, also known as saw palmetto, is alow-growing palm tree native to the SoutheastUS and West Indies [50]. The berries of the palmtree contain fatty acids and phytosterols thathave antiandrogenic activity through inhibi-tion of 5-alpha reductase [51]. It is well knownas an herbal treatment of benign prostatichyperplasia and lower urinary symptoms suchas weak urine flow, hesitancy, incompleteemptying, frequency, urgency, and nocturia[50]. Over the past few years, Serenoa repens hasbecome of interest for potentially treatingandrogenetic alopecia (AGA).

One study found that 320 mg a day of Ser-enoa repens improved AGA in 38% of patientsand stabilized AGA in 52% of the patients, buton the vertex scalp [51]. It is important tomention that this improvement was not as sig-nificant as that in patients treated with finas-teride. In the same study, 68% of patients whotook 1 mg a day of finasteride had improvementof their AGA in both the vertex and anteriorscalp regions [51].

Serenoa repens is generally tolerated well andhas not been associated with any serious adverseevents [50]. The most common adverse eventsreported are abdominal pain, diarrhea, nausea,vomiting, headache, decreased libido, and rhini-tis [50]. Serenoa repens, like other 5-alpha reduc-tase inhibitors, reduces prostate-specific antigenlevels by 50% after 6–12 months of treatment[51]. More studies are needed to assess the role ofSerenoa repens in the treatment of AGA.

CONCLUSIONS

The aim of this review was to aid dermatologistsin better understanding the mechanism of

Dermatol Ther (Heidelb) (2018) 8:5–16 11

action, efficacy, and potential dermatologicbenefits of popular nutraceuticals. For themajority of nutraceuticals mentioned here,patients who consume a healthy balanced dietare most likely obtaining adequate amounts ofthese nutrients to receive the aforementionedskin benefits. However, if diets are lacking keynutritional components, supplementation maybe of benefit to those patients. It is importantfor providers to discuss the benefits and

consequences of nutraceuticals with patientsand to mention the importance of a recom-mended daily allowance as most things con-sumed in excess have the potential to causeadverse effects. With advances in technologyand the expansion of the online consumermarket, it is vital that providers offer anauthenticated, medically certified, and safeavenue to purchasing the recommendednutraceuticals.

Majorsubtype ofnutraceutical

Nutraceutical MOA RDA Oral source Skin function

Amino acids N-Acetylcysteine Increase in red blood cell glycine,cysteine, glutathioneconcentrations; decline inoxidative stress and plasmamarkers for oxidant damage

Not yet established by FNBIM.Further studies needed

Cysteine and glycinesupplementation

Protects against oxidative stress(i.e., DNA damage andaging)

Carotenoids b-Carotene Inhibits free radicals and singletoxygen-induced lipidperoxidation; decreases MMP-9activity

Supplemental all-trans-b-carotene:1800 lg/day for men;1400 lg/day for women.Dietary all-trans-b-carotene is10,800 lg/day for men;8400 lg/day for women

Green leafyvegetables, orangeroot vegetables,yellow or orangefruits

Scavenges ROS to protectagainst oxidative stress anddecrease UV exposure;protects against ECMdegradation

Carotenoids Lutein andzeaxanthin

Blocks damaging blue wavelengthsand prevents free radical damage

Not yet established by FNBIM.Proposed quantity: lutein6–10 mg/day and zeaxanthin2 mg/day

Green leafyvegetables, eggs

Antioxidant and decrease UVexposure

Carotenoids Lycopene Singlet oxygen quencher; decreasesMMP-1 activity; induces cell-cyclearrest and induces apoptosis

Not yet established by FNBIM.Further studies needed

Tomato paste,tomatoes, pinkgrapefruit,watermelon

Lowers UV-induced erythema;decreases collagenbreakdown; inhibitsproliferation of certaincancer cells; decreases skinroughness

Fatty acids a-Linolenic acid(ALA),eicosapentaenoicacid, anddocosahexaenoicacid

Inhibits formation of pro-inflammatory cytokines (i.e.,prostaglandins, leukotrienes);decreases prostaglandin-E2production

Not yet established by FNBIM.Adequate intake for linoleicacid: 17 g/day for men and12 g/day for women ages19–50; 14 g/day men and11 g/day women ages 51?. AIfor ALA 1.6 g/day men and1.1 g/day women, ages 19?

Flaxseed oil, canolaoil, hemp seed oil,cold-water fish(salmon, trout),nuts, seeds

Anti-inflammatory; reducesUVR-induced inflammation;increases MED

Minerals Copper Cofactor in enzymatic reactions forcollagen crosslinking with lysyloxidase and skin pigmentationwith tyrosinase; promoteskeratinocyte and fibroblastproliferation

900 lg for men and women ages19?

Nuts, seeds, seafood,meat, grains

Collagen crosslinking, skinpigmentation, skinrejuvenation, wound repair,anti-inflammatory, and anti-bacterial properties

Minerals Selenium Aids glutathione peroxidases andthioredoxin reductases, removingdamaging lipid hydroperoxides,hydrogen peroxide, peroxynitrites

55 lg/day men and women 19? Meat and seafood Supports DNA synthesis andrepair, cell apoptosis andguards against oxidativedamage, leading to cellmembrane stabilization andprotects against DNAdamage

12 Dermatol Ther (Heidelb) (2018) 8:5–16

continued

Majorsubtype ofnutraceutical

Nutraceutical MOA RDA Oral source Skin function

Minerals Zinc Protects against lipid peroxidation,UVR-induced cytotoxicity, andoxidative stress. Necessary forepidermal proliferation andkeratinocyte differentiation.Hinders intracellular adhesionmolecule 1; decreases nitric oxideproduction

11 mg/day men; 8 mg/daywomen 19?

Non-milled wholegrains, red meat,seafood, fortifiedproducts (i.e.,cereal)

Cofactor for cellular activity anddefense; skin cellproliferation; wound healing;anti-inflammatory properties

Polyphenols Curcumin Hinders production of cancer cells,encourages apoptosis, promotescell death by influencing p53expression and decreases NF-jBproduction. Suppresses pro-inflammatory cytokines.Suppresses ROS production byscavenging free oxygen radicals;inhibits lipid peroxidation.Decreases C-reactive protein

Not yet established by FNBIM.2–8 g/kg/day has beensuggested

Turmeric spice, curry Anticarcinogenic, anti-inflammatory, andantioxidant properties

Polyphenols Epigallocatechingallate (EGCG)

Inhibits lipid peroxidation, limitsUVR-induced DNA damage,reduces ROS and free radicalproduction. Suppresses pro-inflammatory inducers (i.e.,cyclooxygenase-2, MMPs).Supports cell cycle arrest andapoptosis

Not yet established by FNBIM.Proposed upper limit ofapproximately 300 mg/day

Green tea leaves,green tea,commerciallyavailable in whitepowder form

Antioxidant, anti-inflammatory,and anticarcinogenicproperties; reduces UVR-induced erythema/edema

Vitamins;water-soluble

Vitamin C Free radical scavenger; essentialcofactor and electron donorduring collagen hydroxylation.Reduces UVB-induced oxidativedamage. Protects against UVA-induced lipid peroxidation.Decreases malondialdehyde

90 mg/day men; 75 mg/daywomen 19?

Raw red and greenpeppers, oranges,grapefruits,kiwifruit,broccoli,strawberries,Brussels sprouts

Powerful antioxidant;encourages intracellular andextracellular collagenproduction

Vitamins; fat-soluble

Vitamin E; alpha-tocopherol (aT)

Halts formation of reactive oxygenspecies, scavenges free radicals,stabilizes cell membranes, reducesapoptotic cells, minimizesactivation of nuclear factor kappaB (NF-jB)

15 mg/day men and women 19? Sunflower seeds,peanuts, almonds,walnuts, pecans,pistachios, sesameseeds, fruits, andvegetables

Protects against UVB damage;photo-protective properties;increases MED

FNBIM The Food and Nutrition Board of the Institute of Medicine, MED minimal erythema dose, MMP matrix metalloproteinase, UVR ultraviolet radiation

Potential future nutraceuticals

Nutraceutical MOA RDA Oral source Skin function

Aloe sterol Encourage formation of type I

and III collagen in dermal

fibroblasts; decrease

expression of MMP-2 and

MMP-9; potentially

increases hyaluronic acid in

dermal fibroblasts

Not yet established by

FNBIM. Further

studies needed

Not yet

commercially

available

Increase collagen

production, improve

skin elasticity; protects

against collagen and

ECM degradation;

potentially increases

hyaluronic acid in

dermis

Dermatol Ther (Heidelb) (2018) 8:5–16 13

ACKNOWLEDGEMENTS

Funding. No funding or sponsorship wasreceived for this review or publication of thisarticle.

Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thismanuscript, take responsibility for the integrityof the work as a whole, and have given finalapproval to the version to be published.

Disclosures. Dr. Mary Lupo discloses thatshe is a speaker for Allergan, Cutera, Galderma,La Roche-Posay, Merz, Theraplex, and LumityLife, Inc. Dr. Mary Lupo also sits on the Advi-sory Board for Allergan, Galderma, TopMD, andEastern College of Health Vocations, LLC. She isa Clinical Investigator for Allergan, RevanceTherapeutics, and Foamix Pharmaceuticals, Inc.Dr. Mary Lupo is an Alphaeon and TopMDstockholder and has an ownership interest inCosmetic Bootcamp. She is also a consultant forSolta/Valeant and Theraplex. Dr. Skylar Souyoulis a Sub-Investigator for Revance Therapeuticsand Foamix Pharmaceuticals, Inc. Dr. KatharineSaussy has nothing to disclose.

Compliance with Ethics Guidelines. Thisarticle is based on previously conducted studies,and does not involve any new studies of humanor animal subjects performed by any of theauthors.

Data Availability. This manuscript has noassociated data to be deposited.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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continued

Nutraceutical MOA RDA Oral source Skin function

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