Nutrition Exam Prep: Week 1

Definitions/Research Methods and Pathogenesis of Chronic Degenerative

Disease

From what do the health benefits of fruits and vegetables come from?

Additive and synergistic combinations of phytochemicals

Define essential nutrient

Upon withdrawal from the diet, clinically evident signs and sx of deficiency
develop… Upon reintroduction to the diet, the signs and sx are reversed

What is a nutraceutical?

Isolate/concentrate of a substance from a commonly consumed food demonstrated

to benefit the health

What is functional food? Like neutraceutical but derived from the whole food

T or F – Designer food is not a definition but more of a concept? True

Describe the nutritional science perspective of the role of diet in

medicine?

The main goal is to achieve, as intervention, implementation of proven health

promoting diets… then, specific to the presentation of each individual, foods are
added to the general health promoting diet to achieve certain
metabolic/therapeutic outcomes

Give an example

A px presents with hypercholesterolemia. The initial goal is to implement the fruit

and vegetable based diet. Beyond this, specific foods demonstrated to possess
hypolipidemic properties are recommended.

What would such food be considered? Designer food

“Designer foods are t/f typically functiona foods/nutraceuticals (FF/N) but

applied with specific ___________________” Therapeutic applications

Give an example of prescription food:

30 g of extra virgin olive oil/day significantly reduces blood pressure in

hypertensive individuals, increases glucose control in diabetics and lowers LDL

Does the following statement apply more to FF/N or to essential

nutrients… Epidemiological evidence demonstrates a protective role for a
certain type of dietary constituent on a particular disease process? FF/N
Fish consumption decreases incidence of heart disease and soy
consumption decreases the risk of heart disease as well as cancers. Are
the previous examples of FF/N or essential nutrients? FF/N

How is the intervention with FF/N governed? By the way the benefit was
deduced

What is the strategy behind this? To recognize the protective/therapeutic value

of a food and recommend its equivocal inclusion into the diet of the patient

What is the Key concept in FF/N? DOSE

At what dose is the FF/N recommended? At a dose which mimics dietary intake
demonstrated to benefit health in a particular population

What happens if the px is unwilling to adopt the dietary changes

necessary to implement such intervention? A nutraceutical version of food is
considered

What is the second Key concept in FF/N? INTENT

What is the intent? To mimic dietary intake of a population which commonly

consumes the target food

T or F – In essential nutrients, dose and intent differ significantly? True

“Dose of intervention _______________ any dose conceivably achieved

through diet” surpasses

Give an example with Vit C? the recommended adult intake of vit C is

80mg/day… Fruits and veggies based diet delivers 250-400mg per day.
Intervention with supplemental vitC targets 1000-200 000mg/day.

What is the intent in this case? To directly and powerfully impact specific
pathways/processes

Give an example with EPA/DHA? 0.9g (1 dose of fish) is used to prevent heart
disease while 4.0g is used to treat rheumatoid arthritis

Name 2 types of observational research methods? Case control and

Prospective Cohort

What are 3 characteristics of an interventional research method?

Randomized, placebo controlled, blinded

Describe a case control observational research? Start with ppl who are
diseased (case) and compare them to healthy ppl (control)

Give an LDL example: measure LDL in ppl who just had heart attack compare to
ppl who never had one. Higher LDL correlated with heart attack risk.
Describe a prospective cohort study: healthy ppl followed over time. Divided
based on some variable. As disease occurs, correlate variable to incidence of
disease

Give an example using LDL: measure LDL in 20yo women. Continue measuring
LDL every year. As over time, ppl get heart disease, assess correlation to LDL
levels

T or F – For both cohort and case control, correlation equals causation?

False

What must we take into considerations from these correlations? They may
be finding a marker for something else

T or F – in all observational studies there is NO INTERVENTION? True

Describe a randomized control trial? Similar to a prospective cohort in that

subjects are followed over time but there’s an intervention and t/f a placebo group
must also be present. Subjects as well as researchers collecting the data should be
unaware of which intervention has been assigned

What do randomized control trial allow? Direct evaluation of cause and effect

What’s an in vitro study? Any investigation conducted outside of a living body

(test tube, Petri dish).

What are its weaknesses? Very detached from physiological processes and often
relationships demonstrated in vitro do not occur in vivo

What is a review paper comparable to? A book

What is it? IT’s in no way a study of any type! An individual with expertise in an
area will summarize a number of studies regarding a certain topic

What is a meta-analysis? A type of review but that’s considered a type of study

What does a meta-analysis gather? Either intervention studies or

observational studies in a particular field and it then applies mathematical
modeling to be able to consider all the studies gathered as though they were one

“It is therefore a __________ study (typically published by a statistician of,

in our interest, biological endpoints” mathematical

What does, by definition, the term chronic degenerative disease refer to?
A long list of ailments common to the NA population

What are the big 2 CDD? Heart disease and Cancer

What are the 2 leading causes of death in USA 2001? Heart Disease 30% and
CA 23%
What are 90% of Heart disease and 100% of cerebrovascular disease
caused by? Atherosclerosis

What is the other 10% of Heart disease caused by? Diseases of the heart

T or F – a significant proportion of CHF is caused by atherosclerosis? True

Describe the Response to Injury Hypothesis of Atherosclerosis study and

results by Ross in ’93:

In vitro and animal investigation conducted through the 70’s were compiled by
Ross and presented as the above named hypothesis. Experimentally, small
incisions made on the interior surface of an artery resulted in significant plaque
formation w/in a period of months

Name Biologically relevant causes of vascular damage:

HTN, Hyperlipidemia, hyperhomocysteinemia, hyperglycemia, smoking

Which of the above mentioned causes are not oxidant derived? HTN

What happens at the site of injury? Circulating plasma monocytes are attracted to
the sight of injury, migrate through the damaged vascular endothelium, through
the basement membrane and imbed in the intima layer of the artery. The
monocytes differentiate into macrophage and perform 2 actions

What are the 2 actions?

1) secrete hormone-like substances of the immune sys (cytokines, eicosanoids)

sitmulating other circulating immune cells to infiltrate the site of damage
2) begin uptaking LDL cholesterol

T or F – there was a significant prob in the progression of research

deducing the LDL ingestion by imbedded macrophages? True

“LDL uptake by ANY cell occurs through ________________________________”

highly selective receptor mediated uptake

T or F – macrophages are virtually devoid of LDL receptors? True

T or F – macrophages are incapable of uptaking LDL at a rate sufficient to

explain the rate of progression of atherosclerotic plaques observed
experimentally? True
So what’s going on then? In vitro, organic hydrocarbons were added to LDL
cholesterol and incubated with macrophages. Macrophages began to uptake the
“acetylated LDL” at extremely rapid rates. Subsequently, the receptor responsible
for this selective uptake was identified and named The acetyl LDL receptor. But
Acetylation does not occur in vivo. Subsequent in vitro investigations
demonstrated that oxidative modification of LDL resulted in recognition by the
acetyl LDL receptor. T/F there exists an absolute requirement for oxidized LDL to
propagate atherosclerotic plaques.

What is the site of injury termed as the macrophage begins to uptake

LDL? Fatty Streak

What is the next step of the process? Proliferation of the smooth muscle later
of the artery

“Various factors produced at the site of injury act as __________ to this

process” mitogens

“The presence of the fatty streak, in conjunction with the proliferation of

the smooth muscle layer is termed the __________________” atherosclerotic
plaque

What are 2 keynotes to remember of the whole process?

1) Oxidant dependant basis of the process

2) Autoimmune nature of the process

What did the Okada in the Redox Report on Cancer in 2002 come up
with?

3 strike rule of carcinogenesis

What does this stem from?

The realization that direct insult to DNA is responsible for carcinogenic change
(INITIATION). The theory stems from observation that 1 genetic insult in isolation
will rarely lead to initiation

T or F – Observation led to the realization that no less than 3 direct insults

to the genome are required to inititate carcinogenic change within a cell?
True

“It was subsequently demonstrated that genetic susceptibility resulted

from inherited or in utero acquisition of ___ to more strikes” One

T or F – Regardless of the source of carcinogen, the mechanism by which

genetic insult occurs is via reductive attack? False… It’s via oxidative attack

“An extension of these original observation is a growing body of

information linking ____________ to carcinogenesis” chronic inflammation
What is a hallmark characteristic of inflammation? The generation of
oxidative burst
What are the 4 stages of cancer progression? Initiation, conversion,
propagation and metastasis

What is conversion and propagation termed together? Promotion

What does conversion denote? Further genetic abnormalities acquired by an

initiated cell conferring proliferative advantage

What happens in the propagation phase? Converted cells are stimulated to

grow, resulting in a physical observable advantage

What’s the hallmark characteristic of metastasis? The preceding acquisition

of independent blood supply through the process of angiogenesis

“Initiation, conversion and propagation are principlally ____________________

while metastasis is princiapally an _____________________________.” Oxidant
driven process/ immune mediated process