Age, Tanner stage, weight, and height were obtained from the yearly mailed questionnaires.

In 1999, members of the GUTS cohort were asked, “Compared to other people your age, how would you describe your acne?” Possible responses were: I almost never have any pimples, I sometimes get a few pimples, I usually have a few pimples, I sometimes get a lot of pimples, and I usually get a lot of pimples.

To assess the potential for selection bias, we compared the boys who responded to the questionnaire that included the item on acne with those who did not using the Wilcoxon rank sum test for continuous variables and the χ2 test for categorical variables. Age-adjusted Mantel-Haenszel prevalence ratio (PR) was used to identify variables that were significantly associated with acne at P value less than or equal to .10. These were then used in multivariate stratified models to identify statistically significant predictors at a Pvalue of .05 or less and those variables that changed the odds ratio of the variables of primary interest by 10% or more using the frequency procedure with the Cochran-Mantel-Haenszel option in software (SAS/STAT, SAS Institute Inc, Cary, NC).16

In our primary analysis, to more clearly distinguish those respondents with substantial acne from those without, we excluded those who said they had “sometimes a few” pimples and dichotomized the responses between the “almost never” and “usually a few, sometimes a lot or usually a lot” levels leaving 2780 boys for analysis. Furthermore, we tested the robustness of our findings to our method of classifying acne by repeating the analysis with all respondents but dichotomizing the response to the acne question at different levels.

Because we did not know the exact onset of acne and we desired to best simulate a prospective study, we examined the association between diet reported in 1996 and history of acne reported in 1999. We also examined the association between diet responses in 1997 and 1998 separately and the cumulative average of diet responses from 1996 to 1998 and history of acne in 1999. To further reduce the possibility of reverse causation, we repeated the analysis among youths aged 11 years and younger in 1996, an age of low acne prevalence.

In multivariate analysis, we adjusted for age in months at baseline in 1996 (quintiles), energy intake (quintiles), height (quintiles), body mass index (quintiles), and Tanner stage (1 and 2, 3, 4, and 5). The food items were modeled as categories of servings per week or per day. The PR and 95% confidence interval (CI) were calculated for each category of intake and were compared with the lowest category of intake as the reference value. The lowest category of intake for types of milk included low intakes of all types of milk. In tests for linear trend, food intake was modeled as continuous variables of servings per day.

We categorized the energy-adjusted values of each nutrient into quintiles (except for vitamin D from supplements, which was categorized into quartiles) and modeled the PR for each quintile with the lowest quintile as the reference category. In tests for linear trend across quintiles of nutrient intake, we assigned the median measured value to each category and used these values as a continuous variable. Missing value indicators were created for those with missing covariates because we had few missing data.17, 18 We present two-sided 95% CI for all PR.

Boys who did not respond to the 1999 questionnaire that was used to define acne were slightly older (mean age = 144 compared with 141 months) than those who did, otherwise there was no notable difference between the two groups. Most of the boys (45%) drank whole or 2% milk, 23% drank low-fat milk, 29% drank skim milk, 0.4% drank soy milk, and 3% did not drink milk at baseline in 1996. Some 79% of the boys reported sometimes a few pimples or more whereas 44% reported usually a few or more pimples. Table I shows the age-standardized prevalence of the risk factors for acne according to categories of total milk intake in the cohort. Calcium, total vitamin D, vitamin D from foods, vitamin D from supplements, and energy intake increased with increasing intake of total milk.

Intakes of calcium, total vitamin D, vitamin D from foods, total fat, types of fat including dairy fat, total vitamin A, and vitamin A from food were not associated with acne. There was a weak positive association with intakes of vitamin D from supplements; the multivariate PR (95% CI; P value for test of trend), adjusted for age at baseline, height, and energy intake, comparing the highest with the lowest quintiles of intakes in 1996 were 1.08 (1.01, 1.15; 0.04). There were no associations between acne and intakes of other dairy foods, chocolate candy, French fries, or pizza (data not shown).

In this prospective study of US boys whose ages ranged from 9 to 15 years in 1996, the most consistent factors associated with prevalence of acne were age, Tanner stage, height, and intake of skim milk. We did not find any association with total fat, dairy fat, total vitamin A, and vitamin A from foods, suggesting that neither these nutrients nor the fat component of milk is important for comedogenicity. We found a weak positive association with vitamin D from supplements.

Milk intake may influence comedogenesis because it contains androgens, 5α-reduced steroids (direct precursors of dihydrotestosterone), and other nonsteroidal growth factors that affect the pilosebaceous unit.19, 20, 21, 22 Many of these bioactive molecules survive processing and, in the case of cheese, fermentation results in the production of more testosterone from precursors in milk.19 The hormones in milk are carried by the whey protein fractions.23 These proteins, including α-lactalbumin, also have intrinsic biological functions.23 Animals fed α-lactalbumin–enriched whey protein show increased will and capacity to engage in physical activities, gains in lean body mass, improved efficiency of exercise training, and decreased percentage body fat mass; all of which are similar to the effect of androgens.24, 25, 26 In addition, α-lactalbumin undergoes pressure-induced conformational alteration, possibly as a result of centrifugation stresses during processing, that leads to changes in biological function.27

Our finding of a definite but weak association between milk intake and acne in boys contrasts markedly with our findings in girls7, 8 but nonetheless provides support for this hypothesis. Girls at this age are at a far more advanced degree of maturation than boys. The insulin-like growth factor (IGF)-I levels in girls peak at age 15 years, and in boys not until 18 years. This cohort of boys was quite immature (average height only 5 ft). They had not yet entered their IGF-I–mediated growth spurt so the findings here are considered as fair representations of the influence of their exogenous (dairy) hormones, less influenced as they are, at this young age, by their endogenous hormones. This is supported by the data on height collected in the same study–the average height of the high milk consumers was 1.2 in (3.0 cm) greater than the nondairy consumers (data not shown).

The amount of androgens in milk has generally been considered low and first-pass metabolism in the liver may further reduce their bioavailability compared with the daily endogenous production in young children and adolescents. However, recent studies have questioned the methodology and assays on which estimates of daily production rates of endogenous steroid hormones in prepubertal children are based28and they suggest that dietary intake may be a more significant source of androgens than previously thought.29 Milk also contains estrogens, some of which are produced in the lactating bovine mammary gland and are direct suppressors of sebaceous gland function.30

Milk intake may also affect comedogenicity through the IGF-I pathway, particularly the ability of IGF-I to increase levels of circulating androgens. In two large cross-sectional studies, milk consumption was positively associated with higher plasma IGF-I levels31, 32 and in both studies, this was predominantly an association with skim milk. Recent studies have suggested that this increase in the IGF-I stimulus to acnegenesis may be mediated by a hyperinsulinemic response to the ingestion of fluid milk.33 In a randomized clinical trial of the effect of milk intake on bone remodeling, intakes of skim and low-fat milk were associated with increased serum IGF-I levels in both sexes.34 Another randomized clinical trial showed that the whey component of milk contains insulin secretagogues.35 Human and bovine IGF-I share the same amino acid sequences36 and several milk proteins, including IGF-binding proteins, protect IGF-I from digestion in the gut.37, 38 Animal studies have shown that milk-borne IGF-I can be absorbed after oral intake.38 Although both serum androgens and IGF-I levels increase at puberty, the period of maximum prevalence of acne, the course of the condition follows the levels of IGF-I more closely than it does androgens.30

Recent work has demonstrated the association of acne with the ingestion of a high glycemic load diet, with improvement occurring on a change to a higher protein, lower glycemic load diet.4 The mechanism suggested for this relationship is through the induction of increased amounts of testosterone by elevated insulin and IGF-I levels secondary to dietary influences. This reinforces the likelihood that synergism of several influences impacting on increased levels of acnegenic androgens is at the root of acnegenesis.

The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3, plays an important role in epidermal differentiation by inhibiting the proliferation of keratinocytes while augmenting their differentiation.39 In studies of hamster sebaceous gland cells in vivo, vitamin D increased the accumulation of wax esters in pilosebaceous units while decreasing the amount of triglycerides. In addition, there is positive biological interaction between the metabolic effects of testosterone and vitamin D in other organ systems, although this has not yet been shown in skin.40 Our findings suggest that vitamin D intake from supplements may have an independent role in acne among boys.