Introducing vitaMedMD™ Prenatal Vitamins

Developing a new standard in prenatal care

“A specialty pharmaceutical company developing a full line of unique products for women’s health issues from menarche through the menopause”

1. Clinical focus IS on achieving levels of nutrient intake that optimizes pregnancy outcome before, during, and after pregnancy

2. Why is that “Clinical Focus” important: Nearly 50% of pregnancies are unplanned Nutritional needs ARE considerably higher prior to conception, during implantation,

during pregnancy, and highest during lactation Recommendations from the CDC and U.S. Public Health Service is that ALL

women of childbearing age should take 400 mcg of supplemental folic acid daily Problem: only 30% of non-pregnant women of childbearing age in the U.S. “report”

taking 400 mcg or more routinely

TherapeuticsMDClinical Focus

1. Importance of folic acid use pre-conception 2. vitaMedMD PNVs advantages over 3rd generation FA

Importance of folic acid use throughout a woman’s life Introduction of Quatrefolic – 4th generation folic acid Importance of DHA in pregnancy and breast feeding

3. MTHFR mutations/polymorphism 4. Importance of elevated homocysteine (HHC) 5. Understanding Thrombophilia and its consequences

TherapeuticsMDProactively Reducing Pregnancy Induced

Risk Factors

4

Why is It So Important in a Prenatal Vitamin?

•Folic acid role well established in prenatal care

‒ Reduction of NTDs, birth defects, anemia, preterm birth, other

•MTHFR Polymorphism

‒ > 50% of women cannot metabolize folic acid

‒ Few women tested

•Quatrefolic® bypasses MTHFR folate polymorphisms and is immediately available for its biological action

•More bioavailable than other forms of folate

Known that humans need to maintain an adequate dietary intake of folate during various stages of their lives

Folate plays an essential role in cell division and DNA synthesis

Folate is involved in human growth and development Folate deficiency has far-reaching NEGATIVE health

consequences at all stages of life Folate deficiency has been implicated in the etiology

of a variety of disorders including but not limited to:

Importance of Adequate Folate Levels

“It has been estimated that as many as half of all birth defects can be prevented if women of

childbearing age consume an adequate amount of folic acid . . .” †

Prevention of neural tube defects (NTDs)1

Reduction of other birth defects (congenital heart disease, urinary tract anomalies, oral facial

clefts, limb defects, pyloric stenosis)Reduction in anemiaReduction of implantation failureReduction in incidence of early (1st trimester) miscarriagesReduction in preterm birthReduction in postpartum blood clots

Benefits of Folic Acid

Reduction in language delay in offspring Reduction in various forms of cardiovascular diseases Reduction in age-related dementia Reduction in onset and severity of Alzheimer’s disease Reduction in prevalence of Osteoporosis Reduction in male infertility (Abnormal DNA) Reduction in all consequences of thrombophilia (increased

tendency of excessive clotting) Reduction in pregnancy-induced headaches

Benefits of Folic Acid

8

Folic Acid and Autism: The Link

A recent study, “The Association Between Maternal Use of Folic Acid Supplements and the Risk of Autism Spectrum Disorders in Children”, by Pal Suren, MD, MPH, was published in The Journal of the American Medical Association (JAMA).

This study examined the association between maternal use of prenatal folic acid supplements and subsequent risk of Autism Spectrum Disorders (ASDs).

9

Folic Acid and Autism: The Link

Key Quotes from the Study

“A case-control study from California of autism spectrum disorder (ASD) showed that maternal intake of folic acid and prenatal vitamins during the 3 months prior to pregnancy and the first month of pregnancy was associated with a lower risk of ASD in offspring, and complementary genetic analysis indicated that the association was modified by gene variants that determine the ability to utilize available folate.” (Referencing MTHFR polymorphism)

“A recent study of 38,954 children in the Norwegian Mother and Child Cohort Study found that maternal intake of folic acid supplements from 4 weeks to 8 weeks after the start of pregnancy was associated with a lower risk of severe language delay at age 3 years.”

“There is also evidence that maternal folic acid supplementation during pregnancy may be associated with reduced risk of other neurodevelopmental disorders in children.”

10

Telomere dynamics: the influence of folate and DNA methylation

1. Telomere shortening/dysfunction is now recognized as increasing degenerative disease risk.

2. Recent studies have suggested that both dietary patterns and individual micronutrients--including folate--can influence telomere length and function.

3. Folate is an important dietary vitamin required for DNA synthesis, repair, and one-carbon metabolism within the cell.

4. Recent published knowledge identifies the residual knowledge gaps. Specifically, this review addresses whether it is plausible that folate deficiency may (1) cause accelerated telomere shortening

(2) intrinsically affect telomere function

(3) cause increased telomere-end fusions and subsequent breakage-fusion-bridge cycles in the cell

Ann N Y Acad Sci. 2011 Jul;1229:76-88. doi: 10.1111/j.1749-6632.2011.06101.x.

11

Telomere dynamics: the influence of folate and DNA methylation

A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes

Telomere regions deter the degradation of genes near the ends of chromosomes by allowing chromosome ends to shorten, which necessarily occurs during chromosome replication

Without telomeres, the genomes would progressively lose information and be truncated after cell division

Over time, due to each cell division, the telomere ends become shorter (aging!!!)

12

Telomeres

TherapeuticsMDNeural Tube Defects (NTDs)

TherapeuticsMDFolic Acid in Preventing NTDs

Epidemiology 2003, March;14(2):200-5 Used data from 23,228 women Predominantly from the NE area of the U.S. Enrolled 1984-1987 Prospective study of early prenatal exposure and

pregnancy outcomes NTDs ascertained through PN testing and by report of

the delivering physician Diet and vitamin intake data gathered in early 2nd

trimester

TherapeuticsMDFolate intake and NTDs: dose-response

Dietary folate equivalents (DFEs) Compared with women having the lowest total

intakes of 0-149 folate equivalents (in mcg): Prevelance of NTDs declined by

34% with intake between 150-399 mcg 30% with intake between 400-799 mcg 56% with intake between 800-1199 mcg 77% with intake of > or = to 1200 mcg

TherapeuticsMDFolate intake and NTDs: dose-response

TherapeuticsMDDose-Response Relation of FA & NTDs

18

Folate/Folic Acid: Is There a Difference?

• Folate is the naturally occurring form of this B-vitamin that is found in foods‒ Only ~50% of natural folate is utilized by the body

• Folic Acid ‒ Synthetic form‒ Variable absorption in both food and multivitamin preparations‒ Requires absorption and transformation into the biologically active

form• MTHFR Polymorphisms

19

Folic Acid

• 1st Generation

‒ Folate (food)

• 2nd Generation

‒ Folic acid (synthetic folic acid)

• 3rd Generation (Metafolin®)

‒ 5-methyltetrahydrofolate calcium salt (reduced folate)

• 4th Generation (Quatrefolic®)

‒ Glucosamine salt of (6S)-5-methyltetrahydrofolate (L-Methylfolate)

20

Folic Acid: Absorption and Transformation

Folate must be transformed into the 5-methyltetrahydrofolate (5-MTHF) form which then passes by diffusion from blood into all body cells and then can convert homocysteine to methionine for DNA and protein synthesis.

21

Folate Methylation

• Methylenetetrahydrofolate reductase (MTHFR): metabolizes folic acid to the active form of folic acid

5-methylfolate

• Over 50% of pregnant women have MTHFR polymorphism and cannot fully metabolize folic acid to its active form

• 4th generation Quatrefolic® is structurally analogous to 5-methylfolate available for its immediate biological action

®

22

• Glucosamine salt of (6S)-5-methyltetrahydrofolate

• Structurally equivalent to the reduced and active form of folic acid (5-methyltetrahydrofolate)

• Immediately available and active form

• Greater bioavailability and stability when compared to the 3rd generation calcium salt

4th Generation Folic Acid

S. Ismaili. Crossover Comparative Bioavailability Study of 5-Methyltetrahydrofolate Glucosmaine Salt (GN10G) Compared to the Reference Metafolin in Healthy Volunteers. Institute for Pharmacokinetic and Analytical Studies. Ligornetto, Switzerland.

MTHFR = Methylenetetrahydrofolate Reductase The enzyme limiting step responsible for metabolizing folic

acid to 5-methyltetrahydrofolate Due to a genetic variation, up to 50% of patients may

have an enzyme that functions less efficiency 4th-generation Quatrefolic, the glucosamine salt of (6S)-

5-methyltetrahydrofolate is structurally analogous to the reduced and active form of folic acid 5-methyltetrahydrofolate

vitaMedMDMTHFR and Quatrefolic

Quatrefolic

Quatrefolic does not require transformation and exists in the active form of folate for its immediate biological action

Quatrefolic has been shown to be more bioavailable than other forms of folate

Quatrefolic increases hemoglobin levels better than folic acid

Quatrefolic reduces homocysteine levels better than folic acid

Polymorphism (biology)(meaning "many" "forms") is a discontinuous genetic variation where two or more forms exist in the same species within the same population. It can apply to biochemical, morphological, and behavioral characteristics, but must be discontinuous

Types of MTHFR polymorphisms Homozygous (C667T) both alleles Heterozygous (C667T) single allele Compound Heterozygous (C667T and A1298C) alleles

vitaMedMDMTHFR Mutation/Polymorphism

Prevalence of MTHFR Polymorphism Among Ethnic

Groups

Ethnicity MTHFR Variant FrequencyC677T A1298C

Caucasian 24-37% 29-37%

Hispanic 31-48% 15-24%

African American 8-15% 12-19%

Asian Indian 10% 27%

Asian – Chinese, Japanese, Korean 33-51% 15-25%

1. Thrombophilia is a medical term used to describe the condition where the blood has an increased tendency to clot secondary to:

Excess of certain proteins, called blood clotting factors, or Inadequate anti-clotting proteins that limit clot formation

2. Can be inherited (15% of people in U.S.) or acquired later

3. Estimated that > 600,000 Americans die/year of blood clots

4. Acquired type usually related to a specific cause like trauma, prolonged periods of bed rest after surgery, cancer, ingestion of oral hormones (BCPs, HRT)

vitaMedMDThrombophilia

5. Most people with a thrombophilia have no symptoms

6. Others develop thrombosis like: DVTs (legs) VTEs (Pulmonary emboli) Strokes Heart attacks Dementia Alzheimer’s Migraine Headaches Pregnancy-induced Headaches

vitaMedMDThrombophilia

• 7. Most common inherited (autosomal dominant) types

• Factor V Leiden mutation (2-8%) = mutation causes protein to be inherited as an abnormal shape preventing it from being broken down properly by proteins C and S which leads to blood clot formation

• Prothrombin mutations (2%)

• Antithrombin deficiency (<1%)

• Protein C deficiency (<1%)

• Protein S deficiency (<1%)

vitaMedMDThrombophilia

vitaMedMDThrombophilia

8. Most common acquired type is (APS)antiphospholipid syndrome

Occurs in 5-10% of pregnant women Body makes antibodies (autoimmune disorder) that

attack certain fats (phospholipids) that line the blood vessels leading to blood clot formation

1. Spontaneous miscarriage 2. Repeated miscarriages 3. Repetitive pregnancy losses (at any gestational

age) 4. Pre-term labor 5. Placental abruption 6. Preeclampsia 7. PIH 8. Postpartum hemorrhage

vitaMedMDAPS and Pregnancy

1. Depends on specific type of thrombophilia 2. Past history of repetitive pregnancy loss 3. Past history of a blood clot

Anticoagulant therapy (ASA, Lovenox, Progesterone supplementation, vitaMedMD products)

Treat throughout pregnancy and postpartum

vitaMedMDAPS and Rx in Pregnancy

1. DHA (Docosahexaenoic acid) is the most abundant omega-3 fatty acid in the human body

2. It is found in every tissue of the body and makes up 97% of the omega-3 fatty acid in the brain and 93% in the retina

3. Few individuals get the recommended daily amount of DHA from our diets

4. Numerous studies support supplementing your diet with DHA with positive benefits for your health

vitaMedMDImportance of DHA

Brain (increased cognitive activity, decreased risk of dementia or memory loss, may slow progression of Alzheimer’s disease, supports cognitive function throughout life)

Eyes (decreased progression of ARMD, decreased progression of Glaucoma, decreased symptoms of DES)

Heart (stabilizes heart rhythm and improved vascular reactivity)

Increased gestational length of pregnancy Improved blood lipid profiles for individuals with high lipids

(lowers triglycerides, lowers LDL, increases HDL) Improvement in attention and intellectual performance Anti-inflammatory effects (arthritis, SLE, SS, bowel

inflammatory disease)

vitaMedMDImportance of DHA

1. Unlike other sources of DHA omega-3, DHA Advantage comes from a vegetarian source (algae)

2. As not from fish, there is no worry of ocean-borne contaminants or risk of fish-related allergies

3. Grown in an FDA-inspected facility 4. Scientific evidence showing DHA much more important

than EPA (eicosapentaenoic acid), major omega-3 in fish oils

5. Presence of EPA, present in fatty fish, is less important in advancing health issues and often demonstrates the opposite effects on bodily function than the benefits of DHA alone

vitaMedMDLife’s DHA Advantage

38

THANK YOU