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Background: There is increasing evidence to support the relationship between acne vulgaris and diet.
Objective: The aim of this study was to investigate possible associations among dietary glycemic index,
glycemic load, milk consumption, insulin resistance, and adiponectin levels in the pathogenesis of acne vulgaris.
Methods: The dietary glycemic index, glycemic load, milk consumption, fasting glucose, insulin, insulin-
like growth factor)-1, insulin-like growth factor binding protein-3, adiponectin, and homeostasis model
assessment of insulin resistance values of 50 patients with acne vulgaris and 36 healthy control subjects
were measured.
Results: Glycemic index and glycemic load levels were significantly higher (P = .022 and P = .001,
respectively) and serum adiponectin levels were significantly lower (P = .015) in patients with acne than in
the control subjects. There was an inverse correlation between serum adiponectin concentration and
glycemic index (P = .049, r = 0.212).
Limitations: This study used a cross-sectional design and the study population was limited to young,
nonobese adults.
Conclusion: A high-glycemic-index/-load diet was positively associated with acne vulgaris. Adiponectin
may be a pathogenetic cofactor contributing to the development of the disease. Further research on
adiponectin levels in patients with acne in terms of development of insulin resistance might be important in
this possible relationship. ( J Am Acad Dermatol 2016;75:155-62.)
Key words: acne vulgaris; adiponectin; forkhead box class O1; glycemic index; glycemic load; insulin
resistance; insulin-like growth factor-1; insulin-like growth factor binding protein-3; mammalian target of
rapamycin complex-1; milk consumption.
A cne vulgaris is a chronic inflammatory dis- elicits endocrine responses and enhances androgen
ease of the pilosebaceous unit.1 Recent synthesis, ultimately affecting the development of
studies have shown a relationship between acne through mediators such as androgens, insulin-
acne and nutritional factors; accumulating evidence like growth factor (IGF)-1, and IGF binding protein
from epidemiologic and controlled dietary studies (IGFBP)-3.8,9 IGF-1 is known to stimulate the key
suggest that high-glycemic-load diets and milk factors involved in acne pathogenesis, including
consumption in particular might promote the deve- keratinocyte proliferation, sebocyte proliferation,
lopment or exacerbation of acne vulgaris.2-7 Some and sebum production.3,9 Smith et al10 showed that
authors are of the opinion that a high-glycemic-index a low-glycemic-load diet results in improvements in
diet induces hyperinsulinemia, which subsequently acne severity and insulin sensitivity, as expressed by
From the Dermatologya and Endocrinologyb Departments, Şişli Reprint requests: Aslı Aksu Çerman, MD, Şişli Etfal Egitim ve Araştirma
Hamidiye Etfal Training and Research Hospital; and Immu- Hastanesi, Etfal S, Halaskargazi Cad 34371 Şişli-Istanbul/Turkey.
nology Department, Marmara University Faculty of Medicine.c E-mail: aksuasli@hotmail.com.
Funding sources: None. Published online April 6, 2016.
Conflicts of interest: None declared. 0190-9622/$36.00
Accepted for publication February 23, 2016. Ó 2016 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2016.02.1220
155
156 Çerman et al J AM ACAD DERMATOL
JULY 2016
the homeostasis model assessment of insulin resis- Patients with a history of any topical or systemic
tance (HOMA-IR), suggesting that nutrition-related acne therapy were excluded from the study.
lifestyle factors might play a role in the pathogenesis Subjects with a history of eating disorders, acute or
of acne. Acne can be related to some endocrine chronic infection, diabetes mellitus (DM), hyperten-
diseases; the most common of these diseases in sion, ischemic heart disease, thyroid disorders,
females is polycystic ovarian syndrome, which is chronic renal or liver disease, polycystic ovarian
characterized by peripheral insulin resistance and syndrome, or amenorrhea were also excluded. All
hyperinsulinemia.11 participants signed a written
Adiponectin is an informed consent form
CAPSULE SUMMARY
adipocyte-derived hormone after being provided with a
that is produced mainly by d High-glycemic-index/-load diets have full explanation of the
subcutaneous fat; it exhibits been implicated in acne pathogenesis. purpose and nature of the
important anti-inflammatory, study, and all of its related
antioxidant, and antidiabetic
d Hypoadiponectinemia associated with
procedures. The study was
effects.12,13 Dietary glycemic a high-glycemic-index/-load diet may
approved by the Şişli
index and glycemic load augment the inflammatory response
Hamidiye Etfal Training and
have been shown to be in patients with acne.
Research Hospital local
inversely associated with adi- d A low-glycemic-index/-load diet may ethics committee.
ponectin concentrations.14,15 have therapeutic potential in acne Factors related to glucose
Adiponectin inhibits proin- management. metabolism and energy bal-
flammatory cytokines and ance that were previously
induces antiinflammatory implicated in the develop-
ones, and it down-regulates adhesion molecule ment of acne and glycemic index and glycemic load
expression, suppresses toll-like receptors and their were examined as possible etiologic factors. The
ligands, and increases insulin sensitivity.13,16 glycemic index values of foods containing carbo-
The objective of this study was to investigate the hydrates were calculated in relation to glucose or
relationships among acne, adiponectin, dietary gly- white bread as a reference food based on the
cemic factors, and insulin resistance. patient’s postprandial blood glucose response and
blood insulin levels. Glycemic load combines the
METHODS glycemic index value and the carbohydrate amount
Participants and protocol to quantify the overall estimated glycemic effect of
The study cohort was designed as 50 patients with standard portion sizes of foods. We also aimed to
acne vulgaris and 36 healthy control subjects, suit- investigate the relationships among dietary glyce-
able for testing for 1 adiponectin enzyme-linked mic index, glycemic load, and acne. For this pur-
immunosorbent assay (ELISA) kit to be worked on pose, the dietary patterns of all participants were
the same day, consisting of 86 plates, when test determined from self-reported weighed/measured
plates were excluded. The acne vulgaris group was food records compiled over the previous 7 days.
recruited from patients admitted to the dermatology Total calorie intake per day, along with mean
outpatient clinic at Şişli Hamidiye Etfal Training and glycemic load and glycemic index and total
Research Hospital, Istanbul, Turkey, and the healthy amounts of carbohydrates, protein, and lipids,
control group from hospital staff volunteers. Subjects were calculated using Australia-specific dietary
with normal body mass index (BMI) (18.5-25 kg/m2) analysis software (FoodWorks; Xyris Software,
were included in the study. Highgate Hill, Australia). Dietary glycemic index
The patients with acne vulgaris were subdivided and glycemic load were calculated using
into the following 3 categories according to the the following equations: dietary glycemic index =
International Consensus Conference on Acne classi- S(glycemic index for food item 3 proportion of
fication system: mild (few to several comedones, total carbohydrate contributed by item) and dietary
papules, and pustules; no nodules); moderate glycemic load = S([glycemic index for food
(several comedones, papules, and pustules; few to item 3 its carbohydrate content in grams]/100).
several nodules); and severe (numerous comedones, The glycemic index values used glucose as the
papules, and pustules; many nodules). At the initial reference, and Sydney University’s glycemic index
visit, each patient’s age, sex, weight, height, and and glycemic index database (produced by Sydney
duration of acne were recorded. BMI was calculated University) was accessed from its World Wide Web
as weight (kg)/height (m2). site (http://www.glycemicindex.com).
J AM ACAD DERMATOL Çerman et al 157
VOLUME 75, NUMBER 1
Table II. Dietary glycemic index, glycemic loads, milk consumption, and serum glucose, insulin, homeostasis
model assessment of insulin resistance, insulin-like growth factor-1, insulin-like growth factor binding protein-3,
and adiponectin levels of patients with acne vulgaris and healthy control subjects
Acne vulgaris Healthy control
n = 50 n = 36 P
Dietary glycemic index, mean 6 SD 47.42 6 6.60 44.52 6 6.58 .022*y
Dietary glycemic load, mean 6 SD (median) 79.04 6 23.31 (76.50) 63.36 6 18.50 (62.50) .001zx
Milk consumption [3 dd/wk, n (%) 23 (28.75) 17 (47.2) .911*
Glucose, mg/dL, mean 6 SD 84 6 7.72 83.67 6 8.33 .849z
Insulin, U/mL, mean 6 SD (median) 9.72 6 6.26 (8.40) 9.88 6 4.30 (8.91) .384*
HOMA-IR, mean 6 SD (median) 2.03 6 1.49 (1.70) 2.05 6 0.93 (1.82) .370*
IGF-1, ng/mL, mean 6 SD 312.08 6 109.79 317.33 6 113.25 .723*
IGFBP-3, ng/mL, mean 6 SD 4.97 6 0.83 4.94 6 0.84 .905z
Adiponectin, ng/mL, mean 6 SD 9.93 6 2.29 11.28 6 2.74 .015yz
dd, Average daily portion; HOMA-IR, homeostasis model assessment of insulin resistance; IGF, insulin-like growth factor; IGFBP, insulin-like
growth factor binding protein.
*Mann Whitney U test.
y
P \ .05.
z
Independent samples t test.
x
P \ .01.
Table III. Dietary glycemic index, glycemic load, milk consumption, serum glucose, insulin, homeostasis model
assessment of insulin resistance, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and
adiponectin levels according to acne severity
Acne severity
Mild, n = 13 Moderate, n = 14 Severe, n = 23
mean 6 SD (med) mean 6 SD (med) mean 6 SD (med) P
Glucose 83.46 6 8.04 (83.0) 84.21 6 8.59 (84.5) 84.17 6 7.32 (85.0) .874*
Insulin 7.80 6 3.46 (7.01) 10.74 6 8.55 (7.4) 10.19 6 5.88 (9.4) .269*
HOMA-IR 1.58 6 0.71 (1.5) 2.27 6 2.06 (1.6) 2.14 6 1.4 (1.9) .347*
IGF-1 279.54 6 126.16 (259.0) 317.71 6 106.99 (278.5) 327.04 6 102.56 (327.0) .239*
IGFBP-3 4.55 6 0.92 (4.4) 5.06 6 0.85 (5.4) 5.14 6 0.70 (5.0) .176*
Adiponectin 9.4 6 1.34 (9.9) 10.33 6 2.27 (10.0) 9.98 6 2.72 (10.2) .520*
Glycemic index 44.19 6 5.39 (44.4) 48.06 6 3.34 (48.6) 48.87 6 8.13 (50.0) .035*y
Glycemic load 75.85 6 25.43 (69.00) 81.43 6 27.84 (83.00) 79.39 6 19.73 (82.00) .806*
n (%) n (%) n (%)
Sex
Female 4 (30.8) 9 (64.3) 15 (65.2) .103z
Male 9 (69.2) 5 (35.7) 8 (34.8)
Milk
[3 dd/wk 7 (53.8) 6 (42.8) 13 (56.5) .596z
\3 dd/wk 6 (46.2) 8 (57.2) 10 (43.5)
dd, Average daily portion; HOMA-IR, homeostasis model assessment of insulin resistance; IGF, insulin-like growth factor; IGFBP, insulin-like
growth factor binding protein; med, median.
*Kruskal-Wallis test.
y
P \ .05.
z
Pearson x 2 test.
acne vulgaris. On the other hand, decreased adipo- play an important role in insulin resistance, DM,
nectin levels might suppress anti-inflammatory cyto- and atherosclerosis.13,16,25 Therefore, reduced adi-
kines and activate proinflammatory cytokines (Fig ponectin in patients with acne might be a
6). In 2002, Cordain et al8 reported that the Kitavan contributing factor in the development of DM and
Islanders of Papua, New Guinea, and the Ache cardiovascular disease. Further research on adipo-
hunter-gatherers of Paraguay never develop acne nectin levels in patients with acne in terms of the
and they have markedly lower rates of obesity, DM, development of DM and cardiovascular comorbidity
hyperlipidemia, and cardiovascular diseases. The might highlight this possible relationship; this sug-
authors suggested that the absence of acne in these gestion should be verified through other studies,
societies might be a direct consequence of their low- particularly those involving adult patients with
glycemic-load diets. In 2012, Del Prete et al28 found a postadolescent acne and obese patients with acne.
close relationship between inflammatory acne and Several methodological limitations within this
insulin resistance in male subjects. In study by study warrant further discussion. First, only young
Nagpal et al,29 the prevalence of insulin resistance adults were studied, and the sample size was decided
was significantly higher in male patients with post- according to the size of the adiponectin ELISA kit
adolescent acne compared with the control subjects, and not a power analysis. Second, obesity, as a
however the metabolic syndrome prevalence was confounder, was an exclusion criterion and our
similar in both groups. Our cohort did not include results applied only to nonobese patients with acne
patients with postadolescent acne. Recent studies vulgaris. Third, diet tracking was limited to a week
have suggested that hypoadiponectinemia might and might not represent a long-term diet trend.
162 Çerman et al J AM ACAD DERMATOL
JULY 2016
Fourth, this research study used a cross-sectional patients: a randomized controlled trial. Am J Clin Nutr. 2007;86:
design; because of the nature of this study design, 107-115.
11. Franks S. Polycystic ovary syndrome. N Engl J Med. 1995;333:
interpretations of the results are limited. Lastly, as 853-861.
Smith et al21 indicated in their study, using the fasting 12. Lim S, Quon MJ, Koh KK. Modulation of adiponectin as a
insulin index in small intervention trials might result potential therapeutic strategy. Atherosclerosis. 2014;233:
in an underestimation or overestimation of the 721-728.
relationship between acne and the degree of hyper- 13. Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor.
Clin Chim Acta. 2007;380:24-30.
insulinemia; therefore, it should be noted as a 14. Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB.
limitation of the study. Association between dietary factors and plasma adiponectin
In conclusion, to our knowledge, this is the first concentrations in men. Am J Clin Nutr. 2005;81:780-786.
study to compare adiponectin levels and its associ- 15. Loh BI, Sathyasuryan DR, Mohamed HJ. Plasma adiponectin
ation with dietary factors in patients with acne concentrations are associated with dietary glycemic index in
Malaysian patients with type 2 diabetes. Asia Pac J Clin Nutr.
vulgaris and healthy control subjects. We do not 2013;22:241-248.
suggest that hypoadiponectinemia is a disease- 16. Fantuzzi G. Adiponectin in inflammatory and immune-mediated
specific finding, but that it is most likely associated diseases. Cytokine. 2013;64:1-10.
with a high-glycemic-index/-load diet and might 17. Melnik BC. Linking diet to acne metabolomics, inflammation,
possibly serve as a cofactor that augments the and comedogenesis: an update. Clin Cosmet Investig Dermatol.
2015;8:371-388.
inflammatory response in patients with acne vulga- 18. Danby FW. Acne: causes and practical management. Oxford:
ris. Low-glycemic-index/-load diets may have thera- Wiley; 2015:49-83.
peutic potential in the treatment of acne vulgaris, 19. Melnik BC, John SM, Plewig G. Acne: risk indicator for
because of the beneficial metabolic and immuno- increased body mass index and insulin resistance. Acta Derm
logic effects of these diets. Venereol. 2013;93:644-649.
20. Melnik BC, Zouboulis CC. Potential role of FoxO1 and mTORC1
The scientific guidance of E. Cerman is deeply appre- in the pathogenesis of Western diet-induced acne. Exp
ciated. English-language editing of this manuscript was Dermatol. 2013;22:311-315.
provided by Scribendi. 21. Smith RN, Mann NJ, Braue A, Makelainen H, Varigos GA. The
effect of a high-protein, low glycemic-load diet versus a
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