Establishing Cause and Effect Between
Diet and Disease
One of the challenges faced by nutritional scientists,
when they ultimately make recommendations regarding
what we should and should not eat, is to establish cause
and effect between a dietary element and the subsequent
development or prevention of disease. Figure 1
demonstrates the four primary procedures by which
causality is established between diet and disease.No single procedure alone can establish cause and
effect, nor can any single study prove causality.Observational epidemiological studies can only show
relationships among variables and cannot provide
decisive evidence by themselves either for or against
specific hypotheses. In order to establish cause and
effect between diet and disease, it takes more than just
observational epidemiological evidence. There must
also be biological plausibility in which evidence
gathered from tissue, animal and short-term human
metabolic studies support causality. When observational
epidemiological evidence is augmented by
biological plausibility studies and confirmed by
randomized controlled trials, the case for causality
becomes ever-more convincing.
Best Acne Treatment To Get Rid Of Acne And Acne Scar:Acne & Deit What Is The Relationship?
Diet and Acne : The Most Recent Data
In addition to our ecologic study demonstrating the
absence of acne in the Kitavan islanders of Papua New
Guinea and the Ache hunter gatherers of Paraguay,1
two recent observational epidemiological studies also
support the notion that diet is linked to acne.2,3 In a
retrospective cohort of 47 and 355 women, after
accounting for age, age at menarche, body mass index,
and energy intake, Adebamowo and colleagues found
a positive association between acne incidence and
total (prevalence ratio = 1.22; p=0.002) and skim
(prevalence ratio = 1.44; p=0.003) milk intakes.2 In a
prospective cohort of 6,094 girls, aged nine to 15 years
studied from 1996 to 1999, milk drinking of all kinds
(total, whole, low-fat, and skim) was positively
associated with acne.3 After accounting for age at
baseline, height and energy intake, the prevalence
ratios and p-values were as follows: total milk (1.20;
<0.001),>
Best Acne Treatment To Get Rid Of Acne And Acne Scar:Acne & Deit What Is The Relationship?
Diet and Acne : Under l y i n g P hy s i o l o g i c a l
Mechanisms
Mechanisms
Acne results from the interplay of six proximate factors:
• increased proliferation of basal keratinocytes within
the pilosebaceous duct;
• delayed keratinocyte apoptosis;
• incomplete separation of ductal corneocytes from
one another during desquamation via impairment of
desmosomal disintegration and subsequent
obstruction of the pilosebaceous duct;
• androgen mediated increases in sebum production;
• colonization of the comedone by Propionibacterium
acnes; and
• inflammation both within and adjacent to the
comedone.
Despite the wholesale dismissal of diet as a potential
environmental factor underlying the development of
acne, a large body of evidence now exists that
demonstrates how certain foods and food substances
may adversely influence hormones and cytokines that
influence five of the six previously listed proximate
causes of acne.
Best Acne Treatment To Get Rid Of Acne And Acne Scar:Acne & Deit What Is The Relationship?
The Dietary Glycemic Index
The glycemic index, originally developed in 1981, is a
relative comparison of the blood glucose raising potential
of various foods or combination of foods based upon
equal amounts of carbohydrate in the food.20 In 1997, the
concept of glycemic load (glycemic index x the
carbohydrate content per serving size) was introduced to
assess blood glucose raising potential of a food based
upon both the quality and quantity of dietary
carbohydrate.Table 1 lists the glycemic indices and loads
of various foods and demonstrates that refined grain and
sugar products nearly always maintain much higher
glycemic loads than unprocessed fruits and vegetables.
From an endocrine perspective, the importance of the
glycemic index and load is that they are closely related to
the insulin response. An exception to this general rule
is dairy products, which exhibit low glycemic indices and
loads, but paradoxically elicit high insulin responses
similar to white bread.24 Highly glycemic and
insulinemic foods are ubiquitous elements in western
diets and comprise 47.7% of the per capita energy intake
in the US. Figure 2 shows how high glycemic and
insulinemic foods, including dairy products, set off a
hormonal cascade that may ultimately result in acne.
Best Acne Treatment To Get Rid Of Acne And Acne Scar:Acne & Deit What Is The Relationship?
Dairy Poducts and Acne : New Findings
In addition to having a potent insulin response, similar
to eating a slice of white bread, a recent dietary
intervention showed that a high milk diet for only seven
days caused insulin resistance in a group of 24 eightyear-
old boys. Insulin resistance in turn may promote
acne via the hormonal cascade depicted in Figure 2.
Milk is essentially filtered blood and as such contains the
full complement of hormones that are also present in
blood. Traditional theory held that consumption of
cow’s milk would not result in the transfer of cow
hormones into human circulation for a number of
reasons. First, in industrialized countries, milk is usually
consumed many hours or days after it is initially
procured. Many hormones such as the insulin
secretagogues (GIP, GLP-1) have very short half-lives
(<10>
labile hormones. Further, the acidity of the stomach and
peptidase enzymes in the small intestine would also make
it difficult for any peptide hormones in cow’s milk to
reach the intestines intact with full biological activity.
Finally, the most daunting task of all would be for intact
peptide hormones to cross the gut barrier that normally
prevents intact proteins and large peptides from entering
Best Acne Treatment To Get Rid Of Acne And Acne Scar:Acne & Deit What Is The Relationship?
The Epidermal Growth Factor Receptor
Only 12 short years have elapsed since the discovery that
humans bear a hormonal receptor in their gastrointestinal
tract called the epidermal growth factor receptor
(EGFR). This trans-membrane, hormonal receptor is
very unusual in that it is expressed luminally—meaning
that it faces the gut contents rather than the
bloodstream. The location of the EGFR puzzled
scientists for years—why was it expressed luminally and
what was its function? Since, hormones always arrive at
tissues from the circulation, why should the EGFR face
the gut contents, which in effect are outside the body?
It turns out that the primary function of the luminally
facing EGFR is to stimulate healing and maintain the
integrity of the cells lining the gastrointestinal tract In
humans, the primary source of the hormone (EGF)
which binds to the EGFR in the gut comes from saliva.
Hence by swallowing saliva, the residual EGF contained
in saliva helps to maintain the integrity and promote
healing of the epithelial cells lining the gut.
The EGFR is a promiscuous receptor in that it doesn’t
just bind a single hormone (EGF), but rather binds a
large family of hormones including transforming
growth factor alpha (TGF-α), heparin binding
EGF(HB-EGF), epiregulin (EPR), amphiregulin (AR),
neuregulins 1, 2, 3, and 4 (NRG1, NRG2, NRG3,
NRG4), and betacellulin (BTC).34 Cow’s milk contains
no EGF, but does contain high concentrations of BTC,
amounting to 1.930ng/liter, Additionally, BTC is
quite stable and survives the pasteurization process and
is even found in high concentrations in cheese,36
Further, a low ph, such as may be found in the gut, does
not impair or prevent BTC from binding its receptor.
Finally, bovine milk contains peptidase inhibitors that
prevent human gut enzymes from degrading EGF
receptor ligands.38 In summary, BTC maintains all the
physical characteristics needed to arrive in the gut
intact and with full biological activity. But more
importantly, it can breach the gut barrier and enter
circulation by the transcellular EGFR route as depicted
in Figure 3.
Once within circulation, BTC then has the capacity to
bind EGF receptors bound in all epithelial cells,
including keratinocytes. BTC can bind the specific
receptors depicted in Figure 4.34
BTC from ingested bovine milk may contribute to
the pathogenesis of acne by its ability to increase
keratinocyte cell proliferation and to decrease
keratinocyte apoptosis. Further, BTC up-regulates its
own receptor, thereby causing additional signaling
through the EGF receptor pathway. In support of the
notion that increased flux through the EGF receptor
pathway by exogenous BTC from milk may promote
acne is the observation that EGF receptor blocking
pharmaceuticals cause non-comedonal acne in most
patients who are administered these drugs
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