Supplements in Dermatology

48 Practical Dermatology March 2005

Iuse herbs, vitamins, and supplements because they

extend my pharmacopoeia for helping patients with skindisorders. In some cases, they protect the patient treatedwith pharmaceuticals or surgery. In other cases, they addto the therapeutic effect or allow treatment of chronic dis-

orders with fewer side effects than do conventional therapeuticsalone. They often have actions for which we have no availabledrugs. Understanding their use requires introduction to differ-ent, more patient- than disease-centered healing systems andultimately changes your thinking about how to choose thera-peutic agents for your patients. Although these substances areinherently less potent and dramatic in their effects on clearanceof symptoms than drugs such as steroids, they can be highlyeffective when chosen correctly as part of a complete regimento shift the patient’s inflammation and physiology. As such,they can allow much more appropriate and safe dosing of ourmore potent conventional pharmacologic agents as part of awell-integrated treatment of dermatologic disease.

Past, Present, FutureHerbal extracts differ from single active chemical pharmaceuti-cals in that they contain a mixture of components that worktogether in concert in the plant and may well have a synergis-tic action in treatment.

We’ll discuss supplements here by their mechanism of actionso that they can be easily incorporated into your current treat-ment plans, either to enhance activity or to spare the use ofagents that have untoward effects in your patients. As long as wehave diseases without known causes or cures, it is important tohave access to alternative treatments that have potential effica-cy—even if that has not been proven. Careful observation of theeffects of these products by physicians who have an understand-ing of skin disease, its etiology, and nomenclature could advancethe appropriate use of these products in a more useful way thanthose less trained.

Nevertheless, it is important to preserve the “Baker StreetIrregulars” of the healing arts, who bring us perhaps thousands ofyears of observation and codification of use of plant-based sub-stances from different cultural perspectives. They have alwaysprovided us with the raw material for development of new phar-maceutical treatments. Even more important is the perspectivefor therapeutic choice that alternative healing brings, and thepossibility that such perspective could be applied to prevent themajority of adverse drug eruptions. To make it illegal to obtainsupplements and herbs in adequate doses would not only harmthe majority of Earth inhabitants treated traditionally but wouldalso interrupt the flow of observation and information whichleads to new pharmaceuticals and better protocols for their use.

March 2005 Practical Dermatology 49

In my practice, I use supplements that have physiologicactions helpful to my patient’s condition and which are toutedin the lore to be helpful. That does not necessarily mean thatthere are studies in the literature that support their use inhumans with that condition. I do so because my comfort zonewith those products, or that of my patients, is greater than withthe more conventional alternatives. Searching PubMed foralmost any plant with well-known traditional use will revealthat researchers are already investigating the components andmechanisms of action on relevant laboratory tests.

Dermatology has always incorporated the use of plant-basedmedicines. Podophyllin comes from May Apple. Oatmeal,Aveena sativa, is used in baths to soothe the skin. Other plant-based treatments with documentation in the literature are dis-cussed in previous publications.

SupplementsVitamin C. Vitamin C, ascorbic acid, is an extremely importantvitamin for the skin. It is necessary for proper collagen forma-tion in wound healing and is important as an anti-oxidant andfor maintaining proper immunity. We are familiar with topicalforms of vitamin C, which are purported to have anti-agingeffects on the skin. There is so much literature on vitamin Cthat I will touch the subject briefly and leave it to the reader.

As discussed below, my preference is for a form of vitaminC that is a crude extract from plant sources and contains theassociated bioflavinoids. Anti-oxidants seem to work best inconcert rather than alone, so I use a variety of anti-oxidantstogether for that purpose. The dose I use depends highly on thesituation. I recommend 500-1,000mg one to three times a day,depending on the situation. The RDA is woefully inadequate,especially based on the levels of vitamin C manufactured byother mammals that have not lost that ability as have humans.

Vascular effectsBioflavinoids. The bioflavinoids are some of the most under-used supplements in dermatology. These are polyphenolsderived from plants, which work in the plant, along with vita-min C, to protect it from free radical damage during its time inthe sun. These were known to medical science and then some-how forgotten for several decades as the wave of miracle drugsand antibiotics came into being. Back in 1953, the Nobel Prizelaureate Albert Szent-Georgi hosted a conference on bioflavi-noids and the capillary at the New York Academy of Science.Bioflavinoids seem to protect the capillary from damage.Herbal lore tells us that different bioflavinoids protect differenttissues preferentially. For example, British pilots during WWIIused bilberry to give them better night vision. Citrus fruits his-

torically were used to treat scurvy, as were pine bark and pineneedles.

I use bioflavinoids and vitamin C to treat disorders of capillary fragility. Uncontrolled observation over the past 25years suggested to me that one half to a third of patients with“senile” purpura, or increased tendency to bruising associatedwith old age and skin atrophy, improved with addition of adequate amounts of vitamin C and bioflavinoids. I would use500-1000mg vitamin C two to three times per day along with 1000mg citrus bioflavinoids BID or TID in somepatients. Those who could afford the more expensiveOligoproanthocyanadins (OPCs) got about 1mg per pound ofthe grapeseed or pine bark product. I also use bioflavinoids inpatients with excessive telagiectasias, such as on the face.Patients’ impressions based on their own observations are thattreatment slows formation of new telangiectasias, but this ishighly subjective and hard to substantiate.

Knowledge of how to choose the most effective bioflavi-noids for skin conditions will emerge as dermatologists pooltheir observations about what works in which conditions andcircumstances. Most of the use and observations on plantbioflavinoids clinically probably comes from non-dermatolo-gists at this time.

Anti-inflammatories Quercetin. A large portion of the disorders that we see in der-matology involve itching and redness with underlying inflam-mation. A number of anti-inflammatory supplements andherbs can be used for symptomatic help, which work somewhatlike anti-histamines for the itching. Quercetin, a bioflavinoidfound in onions and many other plants, is one of my favoritesin this group. I give it regularly during the day and suggest thatthe patient take extra during episodes of itching. In some of mypatients who are open to using pharmaceuticals, I have themtake a sedating antihistamine at night to avoid digging at theirskin and use quercetin during the day.

Quercetin has a number of effects on the inflammatory cas-cade, which leads one to believe that it would be useful ininflammatory disorders. These include inhibition of histaminerelease from basophils and mast cells. Quercetin has membranestabilizing effects, in vitro effects on inhibition of steps ineicosonoid metabolism including inhibition of lipoxygenase,and in vitro inhibition of the transcription and activity ofcyclooxygenase-2. Quercetin has also shown to have anti-inflammatory activity in vivo by down-regulating the NFkappa beta pathway. It preferentially decreases TH-2 associat-ed cytokines. Quercetin also enhances apoptosis in tumor cellsand has anti-cancer effects for a number of different cell types.

Chances are you may already be using quercetin, which ispart of the Allium sepium extract incorporated in Mederma

(Merz). Quercetin has been shown to inhibit scar formation,and Mederma has been shown to inhibit scar formation in ananimal model. We have a lot of information implicatingquercetin as being useful in skin disease for its anti-inflamma-tory, anti-oxidant, and other beneficial properties, but we donot have clinical studies on this product. I use quercetin orallyat a level of 200-400mg three times per day, sometimes givingextra doses as needed for itch. Although it may be adequate asan anti-inflammatory alone in only some instances, combinedwith use of other anti-inflammatories it may have more bene-fits. Most of its other effects are protective of the body ratherthan detrimental.

Hepatics Silymarin In my medical training I learned a lot about drugsthat harm the liver but very little about substances that protectthe liver. Herbal lore has a number of hepatics or herbs that havebeneficial effects on the liver. One of the most prominent ofthese herbs is milk thistle or Silybum marianum. Silymarin isactually a collection of these flavonolignans including silybin,silydianin, silychristin, and apigenin. The flavinoids are alsobelieved to act in mammalian tissues as free radical scavengers, aswell as plasma membrane stabilizers, and thus confer protectionto the cells during free radical stress generated by chemical reac-tion or radiation. It makes a lot of sense to use this or otherhepatoprotective herbs when using potentially hepatotoxic med-ications. Years ago, it was brought into this country as the treat-ment for accidental mushroom poisoning. One of the most dra-matic effects of silymarin in humans is in protection againsthepatic damage and death due to ingestion of death cap mush-room and its components phalloidin and alpha amanitin. Anadditional method of hepatic protection against deathcap fungustoxins is prevention of their entrance into hepatic cells by com-petitive inhibition of cell surface receptors.

Silymarin protects the liver by a number of mechanisms. Itsantioxidant activity protects the liver from free radicals generat-ed during biotransformation by the p450 system. It also increas-es the endogenous antioxidant glutathione in the cells and in themitochondria. It protects the cell membranes. It also enhanceshepatic repair and regeneration by favoring regeneration of ribo-somal RNA.

A most intriguing use for Silymarin is to reduce the chancesof developing hepatotoxicity from drugs with that potential. Ihave seen a number of dermatologists on chat lines using sily-marin in this way, despite the lack of published human studies.Hepatocyte culture studies indicate a reduced leakage of enzymeand decreased morphologic evidence of damage after exposure toa variety of drugs when cultures were pretreated with silymarin.

To further reduce the chances of hepatotoxicity, checkwhich p450 enzymes are involved in the biotransformation of


Supplements in Dermatology

the drugs you are adding and the ones the patient is taking,looking for possible competition or activation of enzymeswhich will change the rate of metabolism of drugs whose con-centration is critical. Keep in mind that adequate substrate isnecessary for phase two liver detoxification, the carting out ofp450 activated and solubilized substances ready for excretion.Without such substrate-glucuronides, etc., p450 activatedintermediates will build up and cause more unexplained toxic-ity than by the drug itself. This is no doubt one of the reasonsfor some of the unexplained hepatotoxicity and other idiopath-ic drug eruptions. I have seen this as a cause of inability to wakeup after surgery, which completely baffled the anesthesiologists.One hint is that the patient has had repeated courses of med-ication which, although different, seem to yield successivelymore side effects with each course.

Skin Effects. The anti-inflammatory activity is used in aCanadian product called Rosacure, which is used to reduce theredness in rosacea patients. Internal studies by the companyshow that the 0.7% silymarin-containing product significantlyreduces erythema on the face but not telangiectasia. It com-bines well with metronidazole cream use. In mice it protectsagainst both photo and chemical induction of skin tumors.

Dosage. For the crude seed product, use 12-15gm per day.As a standard extract, silymarin is administered as three to six56-175mg capsules or tablets per day (usually 200-400mg sily-marin per day). As an alcohol tincture, 10 drops to 2ml areadministered three times per day.

Side effects. Most references describe no side effects for thisfood grade herb. There is only occasional mention of slight gas-trointestinal complaints. I am aware of one case of anaphylaxisand one anonymous report of an adverse reaction to milk this-tle in a patient on amitriptyline. Recent in vitro studies suggestthat silymarin may inhibit CP450 3A4 and 2C9, the former ofwhich is involved in amitriptyline degradation. It may be ofbenefit in those who have slow phase II detox due to insuffi-cient substrate.

Horse chestnut. One bioflavinoid which has been well doc-umented in the dermatologic literature for its effect on specifictarget tissues is eschin from horse chestnut for use in chronicvenous insufficiency of the legs. Multiple studies show reduc-tion in leg volume comparable to compression stockings usinghorse chestnut extract. Eschin increases tone, reduces edema,and decreases inflammation. Its effectiveness in the treatmentof varicose veins of the leg has been documented in the derma-tologic literature. The dosage of tablets or tincture should becalculated to deliver about 80-120mg of escin(aescin) per dayin divided doses. Gastrointestinal irritation can occur from tak-ing uncoated tablets, but significant side effects are extremelyrare. It is a useful adjuvant to treatment of both large varicosi-ties and sunburst telangiectasias, in a program including leg

elevation, support hose, sclerosing injections, and Dopplerevaluation for further surgical treatment as necessary.

EnzymesBromelain. Bromelain is an enzyme present in the stem of thepineapple. If taken with meals, it will aid digestion. If taken anhour before meals or two hours after, it will be picked up by theWBCs and aid in the lysosomal pool for breakdown andcleanup as in the remodeling which takes place after injury orsurgery. Studies have shown that bromelain is indeed absorbedas an intact molecule. It is useful in these conditions, as well asin other forms of inflammation. I use two capsules three to fivetimes per day between meals as indicated above. It is known toreduce swelling, pain, healing time, and bruising following sur-gery or trauma. It is also known to be fibrinolytic, affectplatelets, have anti-tumor properties, be anti-inflammatory,and help in debridement. Despite its anti-platelet effects, itdoes not seem to promote bleeding in skin surgery. Keep an eyeon the literature on this. Years ago, a product in the PDRknown as Ananase was available to speed up dissolution ofhematomas.

I had been using bromelain for inflammation and surgeryfor some time, to the occasional rolled eyes of my colleagues. Ialso used a homeopathic product known as Arnica 30C toreduce pain and improve healing after surgery. My colleagues atColumbia University had asked their resident Naturopath forsuggestions to improve their post-surgical results and presentedsuch a regimen at one of the advanced surgical courses at theAAD meeting some years ago. I found that a lot of my patientsundergoing minor surgery needed little or no codeine whenthey used arnica.

Essential Fatty AcidsEvery dermatologist should know about the uses of essentialfatty acids (EFA’s). Early observations indicated that unsaturat-ed oils applied to the skin of parenterally fed children correct-ed an eczema-like scaliness of their skin. Linoleic acid wasthought to be the active ingredient. We now know this to bepart of the omega-6 family of essential fatty acids. One criticalrole for EFA’s is incorporation in the lipid sandwich whichgives skin its barrier capability. Reduction of inflammation andproper body function require a balance between these omega-6and the omega-3 essential fatty acid. This article will focus onthe anti-inflammatory role of omega-3 fatty acids.

Fish Oils. One of my favorites is northern fish oil, such ascod liver oil, which is rich in EPA and DHA. These omega-3unsaturated fatty acids become part of the lipid component ofthe cell membrane. When cyclooxygenase is activated andcleaves off from the cell membrane in the process of producinga lipid message, these omega-3 EFAs lead to the formation of




an anti-inflammatory message of the PGE 3 category, asopposed to aracadonic acid from other plant and animalsources. Omega-3 fatty acids are found in cold-water fish,which live off of cold water microorganisms like krill, whichproduce highly unsaturated EFAs to stay liquid at cold temper-atures.

To make a true difference requires a shift in diet towardomega-3-rich foods, reduction in aracadonic acid-rich foods,and addition of adequate amounts ofEFA-rich oil. Removal of trans-satu-rated fats in the diet, such as in mar-garine or in long shelf-life bakedgoods, is also important. The patientshould not oxidize these EFAs withfree radicals from sun exposure,smoking, medication biotransforma-tion, or excessive stress. Vitamin Eand other antioxidants in the dietprotect the unsaturated bonds. Fishoils have been shown to be helpful inatopic dermatitis but not better thancorn oil in one study.

Northern fish, living off coldwater krill, seem to have the highestconcentrations of EFAs. Large car-nivorous fish, such as swordfish andtuna, seem to have higher concentra-tions of mercury and PCBs. Be surethe fish oils have had mercury, PCBsand cholesterol removed, since fish bio-concentrate these sub-stances. Checking with your health department often revealsthat pregnant women and children are only permitted to eatthem once a month or less. Organized legislative action couldreverse this trend over time.

PhilosophyUnderstanding the how-to of herbs, supplements, and vitaminsin dermatology goes far beyond what substance treats whichconditions. The various conceptual bases by which these sup-plements are chosen to treat a specific patient with a specificdisease have enormous import as a framework for therapeuticdecision-making in dermatology and medicine in general. Eachframework is based on the etiology of the disease process in thatindividual as the events leading to and characteristic of theindividual and the disease are understood by that system.

Synthesizing various systems and scientific medicine, I striveto understand the events preceding onset or aggravation of acondition which may affect function of the individual’s systemin such a way as to bring on the condition. I then treat in the

safest way possible to reverse these aggravations in order toreverse the skin condition. Since herbs, vitamins and supple-ments are closer to foods and spices than drugs, I often choosethese to address the probable links in the causative chain lead-ing to disease manifestation. Thus I might use anti-viral orimmune supportive herbs to address a skin condition whichseems to follow a viral illness. If implications are strong enoughand indications are powerful, as in guttate psoriasis, I might

choose an antibiotic rather than asupplement.

Cautions My biggest concern with supple-ments is in patients on multiplemedications that have narrow ther-apeutic ranges of efficacy and toxic-ity. Interaction by way of alteringhepatic metabolism or serum bind-ing could either lower effective con-centration below therapeutic rangein the case of critical medications,or in other cases, raise the concen-tration to a toxic level.Consultation of the literature withreference to known interaction aswell as which p450 enzymes are uti-lized, up or down regulated, mayhelp solve this dilemma, in con-junction with feedback from the

patient’s internist and an herbalist.

Expanded ThinkingA number of plant and animal derived substances that reduceinflammation and oxidative damage have been discussed.Several of these are forms of polyphenols known as bioflavi-noids, which each have multiple effects on the skin and othertissues. These products are readily available and can be addedto our treatment regimens based on knowledge of both the loreand the basic laboratory data behind them. In some cases, goodclinical studies also support their use. For inspiration, we onlyhave to look around to see how our colleagues in the cosmeceu-tical world have been using these same products in skin creams.

Steps in the pathway toward inflammation or oxidativedamage can be altered using these substances, according toour knowledge of how they work from the literature. As weexpand our thinking to address the underlying physiologybehind each patient’s illness, we will be able to choose bothsupplements and pharmaceuticals with more efficacy and fewerside effects.


Careful observation of the effects

of these products by physicians

who have an understanding of

skin disease, its etiology, and

nomenclature could advance

the appropriate use of

these products.

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Supplements in Dermatology