How diet affects skin- specifically acne

Sandra Hipsz
Earl Marriott Secondary
There has been much speculation over the years of the role diet plays in the
causation of acne. From the information I have gathered through research, I have come to
the conclusion that there is a definite link between what we eat and acne. I asked the
following questions prior to my research; what chemical reactions occur to cause acne?
What foods contribute to the cause of acne and why? How can we get rid of acne through
change in diet?
First off, how does acne "happen"? Acne occurs when glands (called sebaceous
glands) in the follicles of the skin become over active. These glands produce sebum, an
oily substance that helps to stop the skin from drying out. Someone with acne produces
too much sebum, which forms a plug with dead skin cells and blocks the follicle. (Funk,
Wagnalls, 2014)
Ongoing research has revealed the role of androgens follicular retention
hyperkeratosis, increase sebaceous lipogenesis, increase colonization with P. acnes,
inflammatory signalling, and regulatory neuropeptides involved in this multifactorial
process, which may influence the hereditary predisposition to develop acne. (Melnik, BC,
2010)
There is increasing evidence in support of the interplay of growth hormone (GH)
insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, which may
have a causal role in pathogenesis of acne by influencing adrenal and gonadal androgen
metabolism. High milk consumption exacerbates acne by increasing the insulin/IGF-1
signalling. Occurrence of acne as a part of various syndromes associated with insulin
resistance also provides evidence in favour of correlation between IGF-1 and acne.
(Melnik, BC; Schimtz, G, 2009)
UNDERSTANDING OF SEBAEOUS LIPOGENESIS
The root of acne lies at the juncture of hormone action and lipid metabolism in
sebocyte differentiation. Acne will not develop without sebum, and sebum will not be
produced without androgenic stimulation of sebocytes. Common inflammatory acne only
occurs when androgens rise at puberty. Basic research suggests that compensatory insulin
excess independently aggravates the acne.(Chen, W; Obermayer-Pietcsh, B; Hong, JB;
Melnik, BC et al., 2011) (Thioboutot, D, 2004)

HYPERINSULINEMIA AND IGF-1 LEVELS STIMULATE SEBACEOUS

LIPOGENESIS
Recent studies have shown that elevated levels of serum insulin-like growth
factor-1 correlate with overproduction of sebum and acne. Even though acne is
considered an androgen-dependent disease, occurrence of acne doesn't correlate with
plasma androgen levels. (Cappel, M et al., 2005) (Deplewski, D et al., 2000)Increased
serum levels of IGF-1 have been observed in adult women and men with acne, giving rise
to the possibility of the role of GH, hyperinsulinemia, and IGF-1 in acne.( Cappel, M et
al., 2005) (Vora, S et al., 2008)
IGF-1 AND ITS ROLE OF INCREASED ANDROGEN SYNTHESIS
Androgens play an essential role in increasing the size of sebaceous glands and
stimulating sebum production. (Zouboulis, CC, 2004) Acne-prone skin exhibits a higher
androgen receptor density
and higher 5alpha - reductase
activity than uninvolved skin.
Conversely, anti-androgens
reduce the synthesis of
sebaceous lipids and improve
acne, whereas androgeninsensitive subjects who lack
functional androgen receptors
do not produce sebum and do
not develop acne.( ImperatoMcGinley et al., 1993)
Hyperinsulinemia
promotes acne by its wellknown androgenic
stimulation to adrenals, testes
as well as ovaries
(Fig.1). (Kumari & Thappa,
2013)
Figure 1

IGF-1 POTENTIATES PERIPHERAL ANDROGENISM VIA FOXO1

PHOSPHORYLATION
Acne occurs in adolescents at a time when GH levels of IGF-1 are highest
(Thiboutot, D et al., 2004). Peripheral of androgen signalling by IGF-1 is said to occur in
two ways (fig. 1)(Melnik, BC et al., 2010). One is by increasing the 5-alpha reductase
activity with increased conversion of testosterone to dihedral testosterone in skin. The
other is alleviating the androgen receptor repression resulting in AR gain-of-function.
(Fan, W et al., 2007)
It was proposed that acne pathogenesis is related to the nuclear transcription
factor forkhead box (Fox 01) deficiency resulting from export of nuclear Fox 01 to
cytoplasm. In the nucleus, AR binds to the AR repressive protein Fox 01. IGF-1 as well
as insulin activates PI3K, which leads to Akt-medicated Fox 01 phosphorylation. As a
result of this phosphorylation, Fox 01 leaves the AR and translocates from the nucleus
into the cytoplasm and hence potentiates the action of androgen receptor. (Melnik, BC et
al., 2008)
HYPERINSULINEMIA, INSULIN RESISTANCE, IGF-1, AND IGFBP3
There is much evidence that high glycemic load diets exacerbate acne by
increasing the levels of IGF-1. It was demonstrated that low glycemic load diet for 12
weeks decreased serum IGF-1 levels and significantly improved acne. Dietary
intervention increases the nuclear content of Fox 01, which normalizes the increased
transcription of genes involved in acne. (Smith, R et al. 2008)
The pancreas responds to hyperglycaemia by releasing large quantities of insulin
to bring down the blood sugar levels. Low blood sugar levels trigger serious craving for
food. With these cravings the tendency is to eat food with high glycemic index and the
cycle continues chronically. (Berra, B et al. 2009)
The more the pancreas releases insulin, the less effective it becomes as a result of
reduced sensitivity of the cells to insulin. (Fig. 1) (Berra, B et al. 2009) This is called
insulin resistance. Chronic hyperinsulinemia in initiates the hormone cascade that favours
tissue growth by stimulating increased levels of free IGF-1 and reducing levels of IGF

binding protein3.(Chiu, A et al. 2003) Because free IGF-1 is a potent mitogen for pretty
much all body tissues, it promotes acne via hyperkeratinisation. Hyperinsulinemia also
increases the number of EGF's and TGFbeta, which elevates the plasma non-esterified
fatty acids. These fatty acids decrease the levels of IGFBP3 and increase the IGF-1
levels.
STUDIES ON RELATIONSHIP OF DIET TO ACNE
Adebamowo et al. (2006) in a prospective cohort study demonstrated a correlation
between milk consumption and acne, but this may be caused by hormones and bio active
molecules present in skimmed milk. Another study done by the same person established
that it is the hydrophilic protein fraction in cow's milk and not the lipophilic androgenic
steroids enriched in milk fat, which increases insulin/IGF-1 signalling with milk induced
aggravation of acne. Milk contains IGF-1. Scientists hypothesise that increased levels of
IGF-1 result in increased sebum production which then causes acne. (Adebamowo, CA et
al. 2008)

STRESS AND INSULIN RESISTANCE

One of many targets of IGF-1 signalling is to repress stress resistance proteins. So
an increase in IGF-1 signalling may decrease the expression of stress resistant genes and
exacerbate cellular inflammation increasing acne. A reduction in food intake reduces the
expression of IGF-1, increasing the expression of stress resistant proteins, and hence may
benefit those with severe acne. (Holzenburger, M et al. 2003)
ENDOCRINE DISRUPTING CHEMICALS AND ACNE
An endocrine-disrupting substance (EDS) is a compound, either natural or
synthetic, which through environmental or inappropriate developmental exposures alters
the hormonal and homeostatic systems. No endocrine system is immune to endocrine
disrupting chemicals including the sebaceous glands. Milk and diet related chemicals
reaching the body may act as EDS and cause acne. Natural chemicals found in human
and animal food (e.g., phytoestrogens) can also act as endocrine disrupters. (Kandaraki, E
et al. 2011)
IGF-1 AND mTORC1

Recent progress in understanding the nutrient-sensitive kinase mammalian target

of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by
both high glycemic load and increased insulin-, IGF-1, and leucine signalling due to milk
protein consumption. Acne should be seen as an mTORC1- driven disease of civilisation.
(Eddey, S 2014)
HIGH GLYCEMIC LOAD AND MILK ACTIVATE THE NUTRIENT-SENSITIVE
KINASE mTORC1
Is there a unifying link connecting nutrient signalling pathways induced by
hyperglycaemic carbohydrates with those of milk consumption? The only way to find out
is if we think of milk and dairy as a species specific endocrine signalling system that
activates a central signalling node in cellular metabolism for stimulation of growth and
call proliferation. Both puberty-induced growth and milk-induced neonatal growth are
driven by the same insulin/IGF-1 pathways, which upregulate mTORC1 signalling. The
endocrinological changes in milk signalling are comparable to the endocrinology of
puberty. Both periods of growth, the milk-driven period of neonatal growth and growth
hormone-driven puberty are associated with elevations in IGF-1, insulin and insulin
resistance. (Fig.2 & Fig. 3) (Melnik, C, 2012)(Burris, J, 2013)

Fig. 1
Figure 3

FOODS THAT CAN HELP RESOLVE ACNE

Eating a more balanced ratio of Omega-3:Omega-6 helps modulate
inflammation in the human body (Simopolous, A, 2002). Omega-3 fats have been shown
to reduce inflammatory cytokine production (Cordain, L, 2005) and inflammatory
leukotriene B4 molecules (Zouboulis, C et al, 2003).Since acne is partially an

inflammatory disease, it makes common sense that anything one can do to limit
inflammation is welcomed.
Multiple studies have been performed on people with acne who are
administered oral zinc supplementation. Overall results show a reduction in acne lesion
count above that of placebo, albeit only moderately. The dosage of zinc in these studies is
normally quite high (Bowe, W, 2010), and more studies are needed to see if the reduction
in acne symptoms could be sustained at lower levels of zinc. However, since other studies
show lower blood zinc levels in people with acne, keeping zinc levels up to par is a
compelling option (Amer, M) (Michaelsson, G; Vahlquist, A; Juhlin, L, 1997). Zinc helps
maintain skin integrity, reduces inflammation, promotes wound healing, helps kill and
suppress acne bacteria, and may reduce skin oil production (Bae, Y et al., 2010) (Jasson,
F et al., 2013).
People with acne tend to have less antioxidants, such as vitamin A, vitamin E,
and selenium, in their skin. It makes common sense that bringing antioxidant levels up to
par would help calm the inflammatory response. However, we do not have enough
evidence at this point to definitively say whether or not antioxidants in food or
supplements help with acne. Topical antioxidants on the other hand, have shown promise
in reducing acne lesion count. Examples of topical antioxidants include green tea,
resveratrol, and licochalcone. (El-Akwaki, Z; Abbel-Latif, N; Abdul-Razzack, N, 2006)
(Michaelsson, G, 1997) (Ozuguz, P, 2013)
CONCLUSION
As a summary, growth hormone (GH), insulin, and insulin-like growth factor-1
(IGF-1) signalling during puberty may have a causal role in pathogenesis of acne by
influencing adrenal and gonadal metabolism. Certain food with high glycemic index and
milk may exacerbate acne by increasing insulin/ IGF-1 signalling pathway. Vitamins, oils
and minerals that can potentially resolve acne include omega-3, omega-6, zinc and
antioxidants. The link between diet and acne is still theoretical and there is much research
to be done but overall there are enough connections to believe that what is eaten affects
skin more than was initially thought.

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