PHARMACIST ROLE IN

PREVENTION OF CHRONIC
DISEASE: 



MICRONUTRIENT DEFICIENCY
INTERVENTIONS
ELIZABETH SHEEHAN
D R . N AT H A N C H A R P E N T I E R
G R A S S F E D FA R M A C Y
MICRONUTRIENT
DEFICIENCY
 WHAT IS A MICRONUTRIENT?
• Micronutrients! vitamins and minerals required in small quantities that
facilitate a normal metabolism, growth and development5
• Called “micronutrients” because their miniscule amounts travel a long way and serve
many purposes in the human body
• Enable the body to carry out functional processes via interactions with specific
hormones and enzymes

Micronutrients are not produced by the body

and must be derived from diet5
*For proper and adequate function, the human body requires both macronutrients (calorie
source) and micronutrients1
ABUNDANCE OF MICRONUTRIENT
DEFICIENCIES
• Micronutrient intake below the recommended concentrations is a growing
problem in the United States
• The CDC states that at least half the children worldwide ages 6 months to 5
years suffer from one or more micronutrient deficiencies, and more than 2
billion people are affected globally6
• Micronutrient deficiencies are most common in poor, children, adolescents,
obese, and elderly4
MAIN REASON
CONSUMPTION OF…
FOR DEFICIENCY:
CALORIE-RICH
MICRONUTRIENT-POOR
UNBALANCED DIET 1

• The general American diet relies heavily on

carbohydrates and fats, known as the body’s
“energy source”
• Why? Inexpensive, delicious(?), easy to
access (gas stations, fast food, convenience
stores), small time required for cooking,
simple to make for adolescents and adults
• This diet causes Americans to easily become
nutrient poor and energy rich, thus cause for
concern1
DEFINING NUTRITIONAL THRESHOLDS

• The dietary reference guidelines below were created by the Institute of Medicines Food
and Nutrition board2
• Estimated Average Requirement (EAR): a nutrient intake value that is estimated to
meet the requirement of half the healthy individuals in a group
• Recommended Dietary Allowances (RDA): the average daily dietary intake level of a
nutrient considered sufficient to meet the requirements of 97.5% of healthy individuals
in each life-stage and sex group.
– 2 standard deviations above the EAR
OBTAINING THE RECOMMENDED DAILY
VALUE
• When the amount of micronutrients falls below the recommended dietary allowance,
this puts the body at risk for a snowballing effect of metabolic disruption
• It is very common that patients will often fall below the RDA, but never experience any
acute symptoms. Absense of symptoms is an inaccurate way of identifying
micronutrient deficiencies, which is why they often don’t become apparent in general
practice4
• Current research shows that the optimum intake of each micronutrient necessary to
prevent disturbance in metabolic and developmental processes is speculated to be
much higher than the current RDA1
THE TRIAGE
THEORY


 Low Grade Micronutrient
Deficiencies and development of



chronic diseases

BY DR. BRUCE AMES

 THE TRIAGE THEORY
Dr. Bruce Ames proposed a theory that explained how the consequences of
micronutrient deficiencies intertwine with human evolution and survival

What is it?
• During a time of micronutrient shortages (deficiency) the functions of micronutrients (40
essential vitamins, minerals, fatty acids, amino acids) are restricted. Our bodies prioritize
the scarce availability of micronutrients for short term survival (organ function) over long
term survival (prevention of age-related diseases like osteoporosis, CVD and cancer)4

• The triage theory provides mechanism behind why metabolic-dependent micronutrients

are reallocated during times of insufficiency
• In other words… “when the body requires nutrients for short-term health and
reproduction, it robs them from organs that are nutrient rich and of lesser importance
in order to sustain major organs that are nutrient poor”4
• When only a scarce amount of micronutrients are COMMON
consumed, the body will use what is available for
short term survival. This leaves the body vulnerable DEFICIENCIES FOR
to the many chronic diseases that are often
prevented by regular micronutrient intake
AMERICANS:

throughout life 

• Osteoporosis
- VITAMIN D

• Cancer
- MAGNESIUM

• Cardiovascular Disease
• Diabetes
- OMEGA-3

• Liver Disease - VITAMIN K

VITAMIN D
 Vitamin D

WHY DO WE NEED VITAMIN D?

A fat soluble
vitamin that
acts as a
steroid
hormone16
• Controls the expression of over 1,000 genes in the human body16
• Regulates the amount of Calcium and Phosphorus in the body by controlling their
absorption17
– Without Vitamin D, only 10-15% of dietary calcium, and 60% of phosphorus are absorbed
• Vitamin D influences the bones, intestines, immune system, pancreas, brain, and
cardiovascular system!15
• Slows down the aging process22
• Aids in preventing chronic disease
– Independent risk factor for total mortality rate in the general population

“Vitamin D deficiency affects nearly 50% of the population

worldwide across all ethnicities and age groups”15
CONSEQUENCES OF INSUFFICIENT
AMOUNTS OF VITAMIN D
• Decrease in absorption of calcium, phosphorus, and bone metabolism which leads to
elevated PTH levels16
• Elevated PTH levels are associated with increase in osteoclastic activity (breakdown of
bone tissue).
– This can result in accelerated bone weakness and decrease in bone mineral density !
leading to osteoporosis and osteopenia
TWO DIFFERENT FORMS OF VITAMIN D
EXIST

Vitamin D2 Vitamin D3
◦ Also known as ergocalciferol16 • THE MOST BIOLOGICALLY ACTIVE FORM*16
◦ Humans do not make this form of Vitamin D
• Also known as cholecalciferol

◦ Produced by some plants when exposed to UV • Primary source: UVB radiation from natural
radiation18 sunlight
◦ Mushrooms!
• Found in cod liver oil and oil rich fish
– Salmon
– Mackerel
HOW DO WE
OBTAIN
VITAMIN
D3?
 VITAMIN D3 – HOW IS IT MADE?
• Activation of Vitamin D requires two hydroxylation in the body for activation20
• FIRST, the liver is where vitamin D3 is converted to 25-hydroxyvitamin D3
• reaction catalyzed by 25-hydroxylase (or the CYP2R1 gene) Calcidiol
• SECOND, in the kidney 25-hydroxyvitamin D3 is converted to the ACTIVE FORM of Vitamin D,
or 1,25-dihydroxyvitamin D20 Calcitriol
• This stage is catalyzed by 1α-hydroxylase (enzyme encoded by the CYP27B1 gene)

It is the active form (1,25-dihydroxyvitamin D3) that binds to the Vitamin D receptor and can be utilized in
the body20
INHIBITING FACTORS OF VITAMIN D
ABSORPTION
• Sunscreen – blocks UVB radiation which is needed to synthesize vitamin D from the sun16
– Wearing sunscreen with SPF 30 reduces vitamin D synthesis in the skin by more than 95%
• Melanin a natural sunscreen built into our skin that blocks the absorption of Vitamin D22
– The darker your skin tone, the less UVB rays penetrate for synthesis
– Those with naturally dark skin require at least 3-5x longer exposure to make the same amount of
Vitamin D as a person with a lighter skin tone
• Body Fat – Vitamin D is stored in the fat thus the more fat present, the lower the bioavailability
of Vitamin D22
– It has been shown that obese individuals have 50% less bioavailability of Vitamin D compared to non-
obese people
• Age – as we age, our skin looses its ability to synthesize Vitamin D efficiently22
• Drugs- Patients taking anticonvulsants and antivirals to treat AIDS/HIV are at risk for
malabsorption because these drugs enhance catabolism of 25-hydroxyvitaminD and 1,25
dihydroxyvitamindD16
VITAMIN D AND AGING

• Telomeres are tiny caps at the end of chromosomes that protect DNA from damage21
– regulate how fast humans age, they shorten every year
– Shorter telomere = aging happens faster
• The longer the telomeres, the slower the aging process happens
• Lack of Vitamin D causes telomeres to shorten21
– Why: It is thought that the anti inflammatory properties of Vitamin D is what slows down the
telomere shortening process
 SOURCES OF VITAMIN D3!
• SUNLIGHT between 10am and 3pm – when the suns rays are the strongest!16
– *Vitamin D produced by the skin may last twice as long in the blood compared to ingested
Vitamin D supplement16
– A sight pink sunburn appearing 24h after initial exposure is said to equate to ingesting
anywhere between 10,000 and 25,000 IU16

HOW DO I KNOW IF I AM DEFICIENT?

• Getting less than <15-20 min of natural sunlight with 70% of the bodies exposure at
least twice weekly without sunscreen23
• Lack fatty fish, fortified milk or foods in daily diet (cereals, nutrition bars, yogurt,
margarine, soy beverages)23
• If you spend the majority of your day inside at work or school or DRIVING
– Windows on cars block almost all UVB rays preventing Vitamin D from being made23
RECOMMENDED
DOSING
• Since Vitamin D is fat soluble, it can
be tricky to get the dosage right
• The 2010 recommended daily
allowance (RDA) for vitamin D is
600 IU for those that are between
the ages of 1-70, breastfeeding,
and 800 IU for those who are over
the age of 7124
– RDA for vitamin D based on
daily intake is only sufficient to
Triage Theory

maintain bone health and

normal calcium metabolism in
healthy people, not to treat
deficiencies, or prevent
chronic diseases!25
• FEW foods are a reliable source of
Vitamin D, supplementation is the
best way to obtain adequate blood
levels25
SYMPTOMS AND DIAGNOSTICS

S Y M P TO M S O F D E F I C I E N C Y 2 6 D I A G N O S T I C PA R A M E T E R S 2 1
• Thinning of the bones, frequent • Deficient ! levels < 20ng/mL
fractures • Inadequate ! Levels < 30ng/mL
• Mood changes, anxiety and depression • Adequate ! Levels > 30-60 ng/mL
• Decreased endurance
• Increased exhaustion with rest • *But keep in mind that 1,000 IU of
Vitamin D raises serum levels only ~5
• Muscle weakness ng/mL*
• Fatigue • So if a patient was in the inadequate
range, the would have to take a LOT
more than the RDI to increase their
Vitamin D levels
MAGNESIUM
WHAT IS MAGNESIUM?

• Essential biologically active mineral that the human body doesn’t

produce28
• Eighth most abundant element in the universe and the seventh most
abundant element in the earths crust 
• Mg is found at the center of the chlorophyll molecule

“56% of the US population is deficient in Mg1”

FUNCTIONS OF MG IN THE BODY 27
• Assists fat, carbohydrate, glucose metabolism
• DNA and protein synthesis
• Activates transport ions across cell membranes**
• Phosphorylation of second messengers
• Cofactor for hundreds of enzymes involved in glucose metabolism, protein production
and nucleic acid synthesis
• Regulates...28
– muscle growth and development
– nerve function
– Blood sugar Levels
– Formation of bone, protein and DNA
– Nervous system function
HOW IS MG ABSORBED?

• After consumption, Mg is absorbed by the small

intestine via passive paracellular transport that is
driven by an electrochemical gradient29
– 40% of magnesium intake absorbed in the small
intestine
– 5% absorbed in the large intestine
– 55% leaving the body as waste
A TYPICAL HEALTHY ADULT HAS A MG STORE OF 25G 30





•
 Intestinal absorption of Mg doesn’t depend directly on the magnesium intake, but rather the
body’s magnesium storage levels30


- 60% IN SKELETAL TISSUE (RESERVES)

- 39% AND 1% IN INTRA AND EXTRACELLULAR REGIONS

WHAT OTHER DIETARY SOURCES HAVE
MAGNESIUM?
• WHOLE GRAINS27
• GREEN LEAFY VEGETABLES
• Seeds – pumpkin, sesame,
• Fish – Salmon
• Beans – black, lima, soy
• Nuts – Almonds, peanuts, cashews, hazelnuts
• Avocados
• Bananas
• Apricots
 PRIMARY CAUSE
OF MG
DEFICIENCY
E AT I N G A C A L O R I C R I C H , M I C R O N U T R I E N T D E F I C I E N T D I E T

( P R O C E S S E D F O O D S , M E AT S , D A I RY P R O D U C T )
WHY ARE SO MANY AMERICANS
DEFICIENT IN MG?
1. Eating caloric rich, micronutrient DEFICIENT foods31
SUCH AS: Processed foods, processed meats, dairy products

2. PHYTATES31
Nuts, seeds, legumes and grains store Phosphorus as Phytic Acid

When we consume the above seeds and grains, Phytic Acid binds to the essential minerals in our
body like Mg, decreasing the amount we can absorb and digest

2. Kidney Excretion31
In a healthy patient, the kidneys filter out Mg, reabsorbing 95% and excreting 5%

In a patient with Type I and Type II diabetes or alcoholism, the excretion rate of Mg can be
doubled- leaving the patient depleted!

MG IS LOST DAILY THROUGH URINE, FECES, AND SWEAT

 LONG TERM HEALTH CONSEQUENCES OF
DEFICIENCY
• Low serum magnesium levels can increase risk of developing:
– COPD
– Metabolic syndrome
– Type II DM1
Triage Theory

• Mg aids the body in breaking down sugar and reduces the risk of Insulin Resistance
• *Patients who consume an adequate amount of Mg will have a lower risk of developing
Type II DM*
– Alzheimer's
– CVD1
– Osteoporosis1
• Mg is a key proponent in bone mineral density
• Study included the investigation of the correlation between magnesium intake and the
risk of Cardiovascular disease, Type II DM, and All cause mortality
• Study population: > 1,000,000 participants
• Follow up period ranged from 4-30 years, the following was reported
– 7678 cases of CVD
– 6845 cases of CHD
– 701 cases of heart failure
– 14,755 cases of stroke
– 26,299 cases of Type II DM
RESULTS

• Study found that dietary magnesium intake of 100mg/day is associated with a

7% DECREASE IN STROKE
22% DECREASE IN HEART FAILURE
19% DECREASE IN TYPE II DIABETES
10% DECREASE IN ALL CAUSE MORTALITY
 The average American ingests around
200-300mg/day of Mg
HOW MUCH
(Far below the RDA) MG AM I
CONSUMING
D A I LY ?
A rough estimate…

Almonds, dry roasted (1 oz.): 80 mg

Spinach, boiled (0.5 cup): 78 mg

Cashews, dry roasted (1 oz.): 74 mg

Soymilk, plain or vanilla (1 cup): 61 mg

Black beans, cooked (0.5 cup): 60 mg

HOW MUCH DAILY MAGNESIUM IS
NEEDED?
• The RDA for Mg intake is 400mg/day for males and 350mg/day for females31
• However this amount doesn’t ensure maximal function in the body
• Diet surveys in Europe and the US reveal that the daily intake of Mg is much lower than
the recommended amounts
– Daily requirement for magnesium is still hard to achieve through a single serving of any one
of these food items, its best to consume a wide variety of magnesium rich foods to reach the
daily intake.
SYMPTOMS AND DIAGNOSTICS

S Y M P TO M S O F D E F I C I E N C Y 3 3 D I A G N O S T I C PA R A M E T E R S
• Muscle cramps and aches • Blood level below normal range of 1.7- 2.2
• Brittle nails mg/dL33

• Decrease in bone mineral density – But not the greatest indicator of mg levels
because blood levels don’t reflect tissue
• Frequent bone fractures levels
SUPPLEMENTATION
• Should always be considered, even without blood tests because most Americans do not
obtain a sufficient amount from daily diet
• Very SAFE - Mg toxicity is very rare1
• When used as treatment, recommended doses are between 250-600mg daily33
• Mg supplements can often cause diarrhea, upset stomach, nausea and vomiting, taking
with food can decrease the chance for side effects
• Mg carbonate and Mg oxide are not recommended for replacement due to decreased
absorption33
– Mg citrate is a better choice in terms of good absorption and less side effects!
DRUG INTERACTIONS

• Magnesium supplements should always be taken 2

or more hours apart from the following
medications33
– Statin Drugs– Mg can reduce statin blood levels
– Tetracycline antibiotics – Mg reduces absorption
– Quinolone antibiotics – Mg reduces absorption
– Sotalol – Mg reduces blood levels and effectiveness
– Gabapentin – Mg reduces bioavailability by 20%
– Levothyroxine – Mg can delay or prevent the
absorption
 

ESSENTIAL
FATT Y
ACIDS
TWO DIFFERENT CLASSES OF POLYUNSATURATED
ESSENTIAL FATTY ACIDS (EFA’S)

OMEGA-3 fatty acids Omega-6 Fatty Acids

• Consisting of… • Consisting of…
– EPA or eicosapetaenoic acid – Linoleic Acid34
– DHA or docosahexaenoic acid
– ALA or Alpha-linolenic acid34

*CALLED ESSENTIAL FATTY ACIDS BECAUSE THE BODY CANNOT

SYNTHESIZE THEM*
WHERE ARE EFA’S FOUND IN FOOD?
Omega-3 Omega-6
• Fatty Fish! EPA and DHA that fish • Vegetables oils (Corn, peanut,
store in fat come from ingestion of sunflower, olive oil)35
microalgae like zooplankton and
phytoplankton35
– Salmon
– Herring
– Mackerel
– Sardines
 IDEAL RATIO OF OMEGA-6 TO OMEGA-3 IS 1:1



HOWEVER 



THE AVERAGE AMERICAN DIET YIELDS A ~20:1
RATIO

• This disproportionality is due to the amount of Omega-6’s found in the typical American diet that is heavy in
refined oils
• A high omega6:omega3 ratio is also due to carrying the APOA5 gene, causing elevated triglyceride levels
• What humans lack in Omega 3’s causes our bodies to use Omega-6 as a substitute
• Omega-3 and Omega-6 compete for the same desaturase enzyme – delta-6 desaturase
– ALA binds to delta-6 desaturase where it converts to EPA and then DHA
– Linoleic acid is converted into arachidonic acid, an important proinflammatory molecule!
• It is thought that linoleic acid (omega-6) inhibits EPA sourced from dietary fish oil supplements, thus it
is best to decrease omega-6 fatty acid intake36

DISPROPORTIONATE
RATIOS
 CONSEQUENCES OF SUBSTITUTION

• When Omega-6 fatty acids are used in place of

Triage Theory

omega-3 fatty acids, this leaves the body vulnerable to

develop a variety of diseases including cancer,
diabetes, inflammatory, cardiovascular and
autoimmune disease
 THE EFFECTS
OF OMEGA-3
AND OMEGA-6
FATTY ACIDS
ON CHRONIC
DISEASES 35
A HEALTHY DIET
• BALANCE of Omega-6 to Omega-3
• Epidemiology/dietary intervention studies have
concluded
– an exceptionally high omega-6:omega-3 ratio may
PROMOTE the development of many chronic
diseases
– a reduced omega-6:omega-3 ratio may PREVENT
or REVERSE these diseases33
MO ST PL ANT SEED O ILS
CO NTAIN NO O MEG A- 3 







ANIMAL BASED FATS ARE
W EL L B AL ANCED
B ET W EEN B O T H S O U RCES 







CANO L A O IL IS TH E MO ST
B A L A NCED! 37 



ADEQUATE INTAKE FOR OMEGA-6
ADEQUATE INTAKE FOR OMEGA-3 38
Related to the Triage Theory

BENEFITS OF
H AV I N G A D E Q U AT E
AMOUNTS OF
OMEGA-3
1
 1. ANTI-INFLAMMATORY PROPERTIES 39
OMEGA-6
• Produce arachidonic acid which generates pro-inflammatory prostaglandins that mediate
the inflammatory response

OMEGA-3
• These pro-inflammatory properties are negated by Omega-3 because they inhibit the
conversion of arachidonic acid to prostaglandins and leukotrienes causing a decrease in
inflammatory response
• Reduces serum levels of TNF-alpha, IL-1 (inflammation markers)
– DHA specifically reduced CRP and IL-6 (inflammation markers)

P R O - I N F L A M M ATO RY P R O S TA G L A N D I N S ! (PG)E2, LEUKOTRIENE B4,

THROMBOXANE A2
2. CARDIOVASCULAR DISEASE PREVENTION 39

OMEGA-3
• Reduce triglyceride levels through expression of LPL (lipoprotein lipase), an enzyme that
hydrolyzes lipids – reducing lipid levels
• Protect against:
– Atherosclerosis ! Chronic inflammation leads to atherosclerosis (primary cause of heart disease)
– High triglyceride levels ! which fuel cardiovascular disease
– Hypertension
– Stroke
3. DIABETES PREVENTION 39

• Proinflammatory cytokines such as TNF-alpha induce insulin resistance

– a key player in Type II DM
• Omega-3 have been a proven to play a preventative role in diabetes by
reducing TNF-alpha levels!
• Supplementing with fish oil not only improves insulin resistance but
lowers triglyceride levels- both of which aid in the formation of diabetes
4. WEIGHT LOSS 39

• Omega-3 inhibits lipid uptake into fat cells (adipocytes) which decreases
fatty acid synthesis and increases lipid oxidation (using fatty acids for
production of energy)
• EPA and DHA reduce triglycerol and free fatty acid levels
– All are anti-obesity effects
AMERICAN HEART ASSOCIATION
RECOMMENDATION
• To prevent Cardiovascular disease, individuals should eat 2 servings of fatty, oily fish at
least twice per week
• One serving is equal to 3.5 oz. cooked, or about ¾ cup flaked fish.
– Fatty fish include
• Salmon
• Mackerel
• Sardines
• Lake Trout
• Albacore Tuna
SUPPLEMENTATION
General recommended dose is around 300-500mg DHA + EPA33

S Y M P TO M S O F D E F I C I E N C Y 4 0 D I A G N O S T I C PA R A M E T E R S
• Dry skin, rash • Fatty Acid profile test
• Dandruff, dull brittle hair
• Decrease in sleep
• Mental abnormalities
• Changes in menstrual cycle
VITAMIN K
• Studied different forms of Vitamin K and storage location when in
abundance and scarce
• Found that when the supply of Vitamin K was limited (human deficiency)
the body preferably utilized the small amount of Vitamin K available in the
Liver since it’s an organ crucial for metabolic function
• This leaves the other Vitamin K dependent proteins associated with bone
building, cancer prevention, and atherosclerosis without any nutrient left to
carry out those functions
• Without the protective Vitamin K effects, the body is left vulnerable to
develop age related diseases like cancer, cardiovascular disease and
osteoporosis

OVERVIEW OF VITAMIN K AND THE TRIAGE THEORY 4

• Vitamin K1 (Phylloquinone)
• Vitamin K2 (Menaquinone) MANY DIFFERENT KINDS
O F V I TA M I N K E X I S T 

– Fat soluble 

















B I O L O G I C A L LY A C T I V E
F O R M S O F V I TA M I N K : 

V I TA M I N K 1 A N D K 2 4 



FUNCTIONS OF VITAMIN K 

• Required for proper BLOOD CLOTTING4,11
– The first and foremost function essential to short term survival

• Plays significant role in bone metabolism11

– Vitamin K is a cofactor for the enzyme that converts protein-bound glutamate residues (Glu)
to gamma-carboxy-glutamate residues (Gla) in Vitamin-K dependent proteins
– One of the most important Vitamin K dependent proteins in bone is Osteocalcin
• Without Vitamin K, these proteins will not be activated leaving the bones vulnerable to resorption
and breakdown

• Aids in prevention of artery calcification (important predictor of CVD)4,11

– Vitamin K dependent calcium binding proteins keep calcium out of the arteries and in the
bone, reducing the risk of developing atherosclerotic plaques
VITAMIN K1 (PHYLLOQUINONE)
• K1 is the PRIMARY DIETARY PRIMARY SOURCES – PLANTS4,11
SOURCE of Vitamin K4 • Green leafy vegetables
• Present Dietary Recommended Values • Brussel sprouts
are based on only K1 values
• Kale
• Lipophilic: K1 goes directly to the liver
• Spinach
to activate proteins that are involved in
blood clotting14 • Broccoli
– If humans get a sufficient amount of • Parsley
TRIAGE THEORY

Vitamin K1 in the liver (needed for short • Oils

term survival), the extra K1 is able to
– Cottonseed
remain in circulation to activate the
proteins that pull calcium from the – Canola
bloodstream. Less calcium in the – Olive
bloodstream aids in artery calcification
– Soybean
prevention. The excess calcium is then
circulated into the bones for utilization
VITAMIN K2 (MENAQUINONE)
• Not as abundant in the human body4 PRIMARY SOURCE
• Includes a range of Vitamin K forms • Primarily produced by intestinal bacteria
referred to as the menaquinones-n11 and found in fermented foods4
– n reflects the number of 5-carbon units – Small amounts in cheese and butter
– Main dietary menaquinones are MK-4 to (cannot be fat free)
MK-10 • Natto: soybean product fermented with
• Mostly in circulation bacillus subtilis (rich in MK-7)4
• Has longer half-life and accumulates to • In recent studies Natto consumption has
higher concentration in serum vs. Vitamin been shown to lower prevalence of
K14 atherosclerosis and bone fragility in Japan4
• Assists calcium getting into bones to stop – Currently, Natto is the richest dietary
source of menaquinones known11
calcified plaque formation4
• Associated with decreased risk of
coronary artery calcification
HEALTH CONSEQUENCES OF VITAMIN K DEFICIENCY 4
SYMPTOMS OF DEFICIENCY/DIAGNOSTIC
PARAMETERS
S Y M P TO M S O F D E F I C I E N C Y 1 2 DIAGNOSTIC
• Bleeding (Gum, GI) • Prolonged PT (INR >3.5)9
• Bruising easily • Most sensitive marker: Elevated des-
• Cuts/scrapes/laceration fail to stop gamma carboxy prothrombin (DCP)
bleeding quickly – Protein in Vitamin K Absense
• Anemia • Plasma level of serum Phylloquinone
(K1) below normal range of 0.2-1.0 ng/
mL10
– Only reflection of oral intake
– Suggests low tissue stores
SUPPLEMENTATION
• The current Recommended Adequate intake of Vitamin K1 is 90 ug/day for women and 120 uq/
day for men11
– However, the Institute of Medicine set the Dietary Reference Intake (DRI) for men and women based on
the absence of abnormal bleeding, not general health requirements11
– These lab levels will keep patients from experiencing acute symptoms of deficiency, however these
levels are based only on Vitamin K1 derived from food11
– No current daily intake recommendation exists for Vitamin K211
– Dietary intake examples: 100 gram serving (about ½ cup) of the following13
• Full fat milk – contained 38mcg Vitamin K
• 2% milk – 19mcg
• 1% Milk – 12mcg
• Fat free milk – 5mcg

Food for thought: There is much controversy surrounding the recommended daily intake of Vitamin K and
if it sufficient enough to assist in long term survival protective effects in atherosclerosis, bone breakdown
and cancer4
 SUPPLEMENTATION CONTINUED- K2
• Vitamin K2 is not available for purchasing over the counter, so it is
important to get this essential vitamin either from fermented foods like
Natto or a supplement15
• It can often be challenging to incorporate new foods into a daily diet
which is why supplements are a great way to obtain recommended
daily values
• This supplement represents a sufficient example of daily Vitamin K2
intake when taking once capsule daily. 15
– It is important to note that MK-7 bioavailability is enhanced providing a
slightly higher dose thank typical Vitamin K-1

Remember: Natto supports

healthy blood vessels!15
SUPPLEMENT SAFETY 8
• The only clinically indicated use for Vitamin K is prophylaxis against Vitamin K
deficiency bleeding in neonates and adults
• Currently, there is no documented case of toxicity associated with Vitamin K1 or
Vitamin K2 supplementation
• The European Food Safety Authority assessment of menaquinones as a source of
Vitamin K for nutritional purposes proposed no safety concerns
• In current practice there has been no increase in thrombosis risk when supplementing
with high doses of Vitamin K2 in both rats and humans (in those not taking oral
anticoagulants)
 DO YOUR RESEARCH
• Since the FDA isn’t required to test supplements for their quality prior to sale it is important to do
your research before taking any vitamin over the counter or from the internet
• There are many third parties that test the quality of these supplements to ensure a few essential
things:14
1. The product really contains the exact amount and form of supplement displayed on the label
2. Purity. Meaning that products are free from heavy metals or other excipients that are non-
pharmaceutical
3. Ability to break apart for absorption. Tests how and where the products dissolve in the body to ensure
that absorption correctly takes place

ConsumerLabs.com and Labdoor.com are two reliable sources to obtain quality product information
• The amount of Americans that are
experiencing at least one deficiency is
consistently growing. “Deficiency” is a broad
medical term that typically is associated with
acute symptoms or in some cases the cause of
acute disease. It is important to be able to
distinguish the difference between a clinical
deficiency and a low grade deficiency, which
would not present with acute symptoms.
• The Triage Theory has been proven to explain
how micronutrient deficiencies may not serve
as a threat to a patients short term health,
TRIAGE THEORY
however certain vitamin and mineral WRAP UP
deficiencies can predispose patients to serious
long term chronic disease states
• To avoid the detrimental health effects
associated with micronutrient deficiencies and
chronic disease states it is best to eat a well
balanced diet and supplement where gaps
exist!
PITFALLS
• Current RDAs are only thought to keep patients from experiencing acute
symptoms however “the optimum intake of each micronutrient necessary
to maximize a healthy lifespan remands to be determined and could even
be higher than the current RDA”1
• Many positive studies discussing the prevention of chronic diseases with
Vitamin K, Vitamin D, Omega-3 and Magnesium exist, however treatment
trials are not consistently reproducible
• Treatment trials extend over a short period of time compared with dietary
inadequacy which can last for many years
• To develop recommendations for dietary intakes more data is needed to
evaluate nutritional requirements across the life cycle, not just a few
years or months
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National Academies Press (US); 1998. What are Dietary Reference Intakes? Available from: https://www.ncbi.nlm.nih.gov/books/NBK45182/
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for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. 3, Overview of Vitamin D. Available from: https://www.ncbi.nlm.nih.gov/boo
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