Abstract
For decades, it was thought that many common dermatological conditions had no relationship to diet. Studies from recent years, however, have made it clear that diet may influence outcome. In this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in skin cancer and aging of the skin. In others, dermatological disease may be linked to systemic disease, and dietary changes may affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed for dermatological disease, such as steroids, are known to raise the risk of other diseases, and dietary change may reduce this risk.
Patients often seek dietary advice from their dermatologist, as they frequently link many of their health problems, including diseases of the skin, to their diet. While some of these concerns are unfounded, research has uncovered significant evidence that dietary considerations may be important in some dermatological conditions.
While a number of well-known conditions are linked to diet, such as food allergies and dermatitis herpetiformis, in this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in skin cancer and aging of the skin. In others, dermatological disease may be linked to systemic disease, and dietary changes may affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed for dermatological disease, such as steroids, are known to raise the risk of other diseases, and dietary change may reduce this risk.
In this article, the authors review studies that have examined the link between diet and dermatology. Many patients come in with questions due to misconceptions that they themselves have developed or due to information they have received from friends, family members, or the media. Dermatologists must take the lead in providing clear, well-substantiated dietary recommendations to their patients.
ACNE
For years, dermatologists have denied a connection between acne and diet, based partially on earlier research. In the 1960s, several research groups explored the relationship between chocolate and acne. The largest study, involving 65 patients, compared the effects of chocolate consumption to placebo over a four-week period, and found no difference in acne severity.1 Based on such studies, many concluded that diet did not impact acne. Researchers recently re-examined this study, however, and found methodological flaws.2
In fact, more recent research has provided strong support for diet as a potential cause of acne. Research has substantiated the role of specific foods, such as dairy products, as well as dietary patterns, including the high glycemic load diet typical of the Western diet.
In the United States, researchers have demonstrated an association between dairy consumption and acne in three separate populations, and a review concluded that the available data is supportive of an epidemiologically weak association between dairy and acne.3-6 Similar findings have been noted by researchers in Italy and Malaysia.7-8 Some studies have noted a stronger connection with skim milk versus other types of dairy. One suggested mechanism relates to hormones. As milk is meant to increase the growth of calves, it naturally contains growth hormones and anabolic steroids.9 Another suggested mechanism relates to the carbohydrate content of dairy products, with related effects on serum insulin and insulin-like growth factor-1 (IGF-1). Finally, many dairy cows in the United States are treated with bovine growth hormone to increase their milk supply, and milk from these cows has been shown to contain higher levels of IGF-1.10
The Western diet has also been researched as a potential cause of acne. It has been noted that acne is absent in native non-Westernized populations, such as in Papua New Guinea and Paraguay. Therefore, investigators have examined the role of the Western diet, which typically corresponds to a high glycemic load diet.11
Glycemic load takes into account the quantity of carbohydrates consumed as well as the rate of carbohydrate absorption. Foods with a high glycemic index, such as sugar, white bread, and white rice, are rapidly absorbed, leading to higher serum glucose levels and corresponding elevated levels of insulin. Insulin and IGF-1 have been shown to augment sebum production, stimulate adrenal androgen synthesis, and increase androgen bioavailability, all of which play a role in the pathogenesis of acne.12
This theory has been tested via randomized controlled trials (RCTs). In one, a 10-week low glycemic load diet resulted in improvement of acne, with histopathological examination of skin samples revealing decreased inflammation and reduced size of sebaceous glands.13 In another, a 12-week low glycemic load diet resulted in improvement of acne, with a corresponding improvement in insulin sensitivity, a reduction in testosterone bioavailability, and a decrease in adrenal androgens.12
SKIN CANCER
Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, and in many patients, will be their first cancer diagnosis. This represents a unique opportunity for dermatologists to introduce the fact that a diet rich in fruits and vegetables may provide overall cancer protection.
Numerous studies have found that a diet rich in fruits and vegetables reduces the risk of cancer. While not all studies have shown benefit, numerous studies, and some of the largest studies, have demonstrated that overall cancer risk is reduced. In addition, greater intake of fruits and vegetables has been associated with a greater reduction in cancer risk.14 While overall cancer risk is reduced, a stronger benefit has been seen with certain cancers, including lung, colon, and upper aerodigestive cancers.15 Laboratory, animal, and human studies have also supported the role of dietary factors in reducing the risk of skin cancer.
Research in this area dates back decades. In a 1975 study of mice exposed to ultraviolet (UV) radiation, 30 percent of mice fed a regular diet developed frank squamous cell carcinoma (SCC). In contrast, only seven percent of those fed a special diet developed SCCs.16 This diet included a mixture of vitamins C and E with glutathione. A later study of mice found that a nutrient mixture added to the diet, which included vitamin C, selenium, and green tea extract, significantly inhibited the incidence of skin tumors.17
Laboratory studies have outlined mechanisms by which dietary factors may impact carcinogenesis. NMSC tumorigenesis is a multistage process, and UV radiation is known to play a major role. Exposure can result in free radicals, which can damage proteins, lipids, and deoxyribonucleic acid (DNA), as well as activate pathways that increase cell proliferation and inflammation.18-19 UV radiation can also lead to immunosuppression, which hampers the ability of immune cells to recognize and combat cancer cells.
Dietary factors may impact this process via a number of different mechanisms. Antioxidants may break down free radicals, neutralize them, or upregulate genes that encode neutralizing enzymes.20 Antioxidants have been shown to reduce UVB-associated epidermal damage and protect against UVB-induced apoptosis.21-22 They also increase expression of genes associated with DNA replication and repair.23
While initial studies focused on well-known nutrients, such as vitamins C and E, beta-carotene, and selenium, studies have supported the effects of multiple other phytonutrients (compounds found in plant-derived foods), including curcumin, lycopene, and genistein, an isoflavone in soy.24~25 Studies have found that compounds, such as grape seed extract, resveratrol (from grapes), and ellagic acid (found in foods such as raspberries) are potent scavengers of superoxide radicals, and that these compounds are able to protect cells from DNA damage.26 In animal studies, polyphenols have been shown to protect the skin from the damaging effects of UV radiation, including a reduction in skin inflammation, oxidative stress, and DNA damage.27
Human studies have also supported the role of dietary factors in reducing aspects of photocarcinogenesis. In one RCT, ingestion of tomato paste, which is rich in lycopene, was found to protect skin against UVR-induced effects, including erythema and DNA damage.28 Other studies have found that ingestion of beta-carotene and lycopene, high in carrots and tomatoes, are able to defend against UVR-mediated damage.29
When looking specifically at skin cancer prevention, human studies have provided conflicting results. When a distinction is made between supplements of isolated oral antioxidants versus dietary intake of whole foods, however, a clearer trend emerges.
Overall, studies of antioxidant supplement use have not supported their role in skin cancer prevention. A RCT found that use of an antioxidant supplement (containing vitamin C, vitamin E, beta-carotene, selenium, and zinc) did not impact the incidence of NMSC.30 In a study of more than 22,000 male physicians, beta-carotene supplementation did not affect the development of a first NMSC.31 A RCT of selenium supplements found no effect on risk of BCC.32
When studies have focused on antioxidant intake via whole foods, however, promising trends have been noted.
In a prospective observational study, researchers focused on the “combined consumption of foods.”33 In this 11-year study, researchers analyzed the consumption of 38 food groups to identify dietary patterns. The meat and fat dietary pattern increased SCC risk, while the fruit and vegetable pattern appeared to decrease SCC risk by 54 percent. In a dietary intervention trial, researchers documented a significant reduction in incidence of NMSC.34 Skin cancer patients reduced the percentage of their calories from fat to 21 percent, along with increasing consumption of beta-carotene, vitamin C, and fiber.35 This intervention resulted in a significant reduction of occurrence of NMSC as compared to controls.
Why have supplements failed in skin cancer prevention, while dietary consumption of whole foods has shown promise? One reason may be due to the biochemistry of antioxidants and their effects. The process of oxidation, and correspondingly antioxidation, is not a straightforward chain of events, but rather represents a finely balanced system. Antioxidants, in neutralizing free radicals, may themselves become pro-oxidant. It has been theorized that whole foods may provide substances to neutralize this newly created pro-oxidant, while isolated supplements cannot.
In consuming a diet based on whole foods, the finely balanced proportion of nutrients, the large number of potentially protective compounds, and the other plant constituents, such as fiber, may all be necessary. Some compounds may potentiate the effects of others, resulting in synergistic effects. This has been documented in both laboratory and animal studies. In a study of murine skin, different combinations of phytochemicals acted as potent inhibitors of skin tumorigenesis, based on documented decreased cell proliferation, decreased markers of inflammation, and a marked decrease of proto-oncogenes.36 All combinations showed either additive or synergistic effects.
In summary, when evaluating in vitro and animal studies, it is clear that certain dietary factors have significant anti-carcinogenesis properties, particularly with regard to UVR-induced carcinogenesis. Human studies of isolated nutrient supplements have not shown benefit. However, intake of dietary antioxidants and phytochemicals in the form of whole foods, particularly fruits and vegetables, has shown promise, and should be recommended. In favor of this approach are the well-known health benefits of consuming a diet rich in plant foods, including the reduction of other types of cancers.
AGING SKIN
Rhytides, sagging of skin, and loss of elasticity are all related to changes in the collagen and elastic fibers of the skin, which are themselves impacted by diet. Ingestion of sugar, in particular, can accelerate these signs of aging, as it promotes cross-linking of collagen fibers.
Cross-linking occurs through a process known as glycation. In this process, a covalent bond is established between the amino acids in the collagen and elastin present in the dermis. These amino acids are linked by glucose and fructose, leading to the production of advanced glycation end products (AGEs). This process is accelerated by hyperglycemia. Research indicates that once established, the body is unable to repair these cross-links. With accumulation of AGEs, structural changes in the skin can occur, resulting in increased stiffness and reduced elasticity.36
Glycation is well underway by early adulthood, with a rate that varies depending on diet.37 Since it remains impossible to repair cross-links, dietary prevention becomes important. While glucose and fructose in the diet are important contributors, other foods, depending on method of preparation, may contain preformed AGEs.38 Once ingested, these can enter the circulation and react with components at the cellular level, causing protein cross-linking. Cooking processes that lead to higher levels of AGEs include grilling, frying, and roasting.39
Research has also focused on foods that may be able to inhibit the production of AGEs. These include herbs and spices, such as oregano, cinnamon, cloves, ginger, and garlic, as well as substances found naturally in certain fruits and vegetables, such as lipoic acid.40-41
PSORIASIS
Studies dating back decades have described the risk of vascular disease in patients with psoriasis.42 In the last decade, this association has been studied more closely, and a number of reports have presented substantial evidence that patients with psoriasis are at higher risk for cardiovascular disease (CVD). While not all studies have confirmed this risk, the evidence is strong enough that patients should be counseled about this association and, more importantly, how to reduce their risk. This includes counseling about cardiovascular risk factors, including those which can be modified through lifestyle changes.
It has been well-demonstrated that patients with psoriasis have a higher prevalence of comorbidities that act to increase the risk of CVD. These include obesity, diabetes, hypertension, and dyslipidemia. A meta-analysis of 27 observational studies found that psoriasis is associated with both an increased prevalence and incidence of diabetes.43 A review of 25 observational studies, with more than 265,000 psoriasis patients, found that psoriasis was significantly associated with greater odds of dyslipidemia.44
In addition, the presence of psoriasis alone may serve as an independent risk factor for myocardial infarction (MI). In a population-based study comparing the risk of MI in more than 130,000 psoriasis patients as compared to more than 500,000 control patients, it was found that patients with psoriasis had an increased adjusted relative risk for MI, even when adjusting for risk factors, such as hypertension, diabetes, and hyperlipidemia.45 In a study of women, psoriasis was found to be an independent predictor for nonfatal CVD.46 In patients undergoing coronary angiography, patients with psoriasis were more likely to have angiographically confirmed CVD as compared to controls. This held true even after adjusting for the presence of cardiovascular risk factors.47 In a study that looked specifically at patients with severe psoriasis, these patients had an increased risk of cardiovascular (CV) mortality, independent of traditional CV risk factors.48
While past theories on the pathogenesis of CVD focused on occlusion, recent theories have focused on the role of vascular inflammation. In a number of studies, increasing severity of psoriasis or longer duration of disease, and therefore more severe or prolonged cutaneous inflammation, has been associated with a higher risk of CVD.46,48 In examining the link between psoriasis and CVD, a number of studies have noted similar pathogenic features, including activation of inflammatory cells and increased circulating levels of proinflammatory cytokines.49 A mouse model demonstrated that sustained cutaneous inflammation promoted both aortic root inflammation and thrombosis, with notable increases in serum levels of proinflammatory cytokines.50
A better delineation of the mechanisms underlying the link between psoriasis and CVD may provide an important rationale for choosing psoriasis therapies in the future. Specifically, it is possible that certain therapies may improve psoriasis while at the same time reducing the risk of CVD. While research has focused on specific therapies, such as the use of biologies, studies to date have not provided definitive answers. However, it is possible to reduce this risk in the current time, without the use of expensive systemic therapies that have the potential for significant side effects.
Dietary intervention should be recommended to patients with psoriasis as a foundational therapy for reducing cardiovascular risk. The initial focus should be on improving conditions known to serve as important cardiac risk factors. Dietary intervention is a foundation of therapy for diabetes, hypertension, and hypercholesterolemia. However, even in patients without these associated cardiac risk factors, a change in diet may help reduce the risk of CVD. A number of studies have shown that certain dietary profiles may be considered “anti-inflammatory.” In one randomized trial, the intervention group was treated with a Mediterranean-style diet. This was associated with improvement in endothelial function scores, as well as a reduction in serum levels of C-reactive protein and interleukin (IL-18).51 As certain eating patterns have been shown to improve markers of vascular inflammation, many physicians now recommend a diet rich in fruits and vegetables, which favors whole grains over processed grains and omega-3 fatty acids over omega-6 fatty acids.
The National Psoriasis Foundation has recommended screening for CVD risk factors in patients as young as 20 years of age. In a study of primary care physicians and cardiologists, however, it was found that most did not routinely screen psoriasis patients for cardiovascular risk factors.52 Dermatologists therefore play a critical role in educating patients about the risks associated with their skin disease. Furthermore, we must encourage patients to take individual responsibility for reducing these risks via behavioral change as well as medical intervention.
SYSTEMIC STEROIDS
A number of systemic medications have potential toxicities, and research is underway to see if dietary interventions may help. For example, transplant patients on multiple immunosuppressive medications have a higher risk of systemic malignancies. In this section, however, the authors focus on systemic steroids, which are widely used in dermatology practice, and for which dietary recommendations are important yet underutilized.
The long-term use of systemic steroids has long been known to increase the risk of hypertension, hyperglycemia, and metabolic abnormalities, in addition to the well-known side effects of increased appetite and weight gain. These side effects, in turn, increase the risk of CVD.
A review of the literature finds a strong focus on medical interventions that reduce the complications of long-term steroid use.53 This includes the use of calcium and vitamin D supplementation.54 While these are important, behavioral interventions, including changes in diet, exercise, smoking, and alcohol use, can have just as powerful a protective effect. With so many potential toxicities due to steroid use, and with their potential severity, it becomes critical that dermatologists address the fact that patients themselves can take measures to protect their health and guard against serious side effects. Dietary recommendations are, obviously, critical in reducing weight gain and reducing the risk of hypertension, hyperglycemia, and metabolic abnormalities. In any patient requiring long-term therapy with systemic steroids, dietary intervention becomes a critical component of our counseling.
SPECIFIC RECOMMENDATIONS
The role of dietary factors in a number of skin diseases underscores an important point about dietary interventions. Weight loss alone is not the goal. Weight loss alone may not improve acne or reduce the risk of CVD or cancer. The goal, rather, should be healthy eating patterns. As physicians, it is important to emphasize that crash dieting or fad diets are not as health-promoting as a sustained focus on healthy foods. This type of dietary change has been emphasized over and over again in the mainstream media, but as physicians, it is important to re-emphasize this point to our patients.
Clearly, recommendations for dietary change should be an important component of patient education for some dermatological diseases. Where should patients seek further information on the specifics of dietary change?
Initial recommendations should focus on evaluation by a primary care physician. This may be supplemented with counseling by a nutritionist who can often provide specific suggestions on how to practically implement a change in diet. In those patients who are unable or unwilling to seek further medical advice, mainstream books may provide some initial guidance.
Broad recommendations for dietary change include well-known, and well-substantiated, specific dietary advice. Patients should increase their intake of fruits and vegetables. They should limit sugar and saturated fat. They should emphasize an intake of foods in their natural state over highly processed foods as well as whole grains over processed grains.
The Dietary Approaches to Stop Hypertension (DASH) trial was a multicenter, randomized study of diet and its effects on blood pressure. It was specifically designed as a trial of dietary patterns rather than individual nutrients and found that the diet substantially lowered blood pressure.55 The diet is high in fruits, vegetables, nuts, and low-fat dairy products, and emphasizes fish and chicken over red meat. It is low in saturated fat, sugar, and refined carbohydrates. A number of books written for the layperson, as well as cookbooks that focus on the DASH dietary recommendations, are available. This type of eating pattern is congruent with what would be recommended initially for patients with psoriasis, skin cancer, and those starting prednisone.
For patients who wish to review the evidence for specific dietary recommendations, the book The Spectrum, by Dr. Dean Ornish, provides substantial support from the medical literature on specific dietary recommendations, and emphasizes that patients do not have to make extreme changes in order to see health benefits.56 Some patients with CVD or risk factors seek more substantial change. Further information on research supporting more substantial dietary change is outlined in The China Study by Dr. T. Colin Campbell.57
CONCLUSION
Dietary interventions have traditionally been an underappreciated aspect of dermatological therapy. Recent research, however, has found a significant association between diet and some dermatological diseases. Dietary interventions may be recommended as therapy, as in acne. Dietary change may help to prevent skin disease, as in aging of the skin or skin cancer. Dietary change may also be an important aspect of prevention of associated systemic disease, as in CVD and other systemic diseases associated with psoriasis or the use of systemic steroids. Dermatologists must be well-educated as to the evidence linking diet and dermatology and must be able to counsel patients appropriately.
Footnotes
DISCLOSURE:The authors report no relevant conflicts of interest.
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