S304- Emerging Treatments of Nutritional Disorders

Erick Hernandez, MD Division of Pediatric Gastroenterology

Miami Children’s Hospital Miami, Florida

Disclosure of Relevant Relationship • Dr. Hernandez(or spouse/partner) has not had

(in the past 12 months) any conflicts of interest to resolve or relevant financial relationship with the manufacturers of products or services that will be discussed in this CME activity or in his presentation.

• Dr. Hernandez will support this presentation and clinical recommendations with the “best available evidence” from medical literature.

• Dr. Hernandez does not intend to discuss an unapproved/investigative use of a commercial product/device in this presentation.

Milestones in the history of pediatric nutrition

1850s Analysis of nutrient content of human and cow’s milk

1880s Estimates of daily caloric requirements of infants

1893 Value of cod liver to prevent rickets

1915 Development of infant formula from cow’s milk

1915-40 Synthesis of vitamins

Pediatric Research (2003) 54. R. E Kleinman, L. A Barness and L. Finberg

Milestones in the history of pediatric nutrition

1940s Long term consequences of malnutrition in children

1956 F. Gomez-malnutrition based on weight for height

1960s Endocrinology of Vitamin D

1960-70 First use of total parenteral nutrition

1990s Genes and genes products related to energy expenditure

1990-02 Resurgence of breast-feeding

Pediatric Research (2003) 54. R. E Kleinman, L. A Barness and L. Finberg

2007/2008 UN Human Development Report

Percentage World undernourished population

Percentage stunting of children under the age of five

2007/2008 UN Human Development Report

1. Iron deficiency is the most common form of nutrient deficiency worldwide

2. Iron deficiency inhibits learning as well as motor and emotional development

3. Individuals exposed to perinatal iron deficiency are at high risk for failing to reach educational milestones later in life

Front. Hum. Neurosci., 23 September. E. C. Radlowski and R. W. Johnson

Iron deficiency and iron deficiency anemia impair neurocognitive development

Nano-iron supplement to treat iron-deficiency anemia

MRC Human Nutrition Research. July, 2014. D Pereira

Iron Oxide

Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 582–588. A Bakshi, S Stephen, M L. Borum, and D B. Doman

Emerging therapeutic options for celiac disease

Engineering gluten-free grains

Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 582–588. A Bakshi, S Stephen, M L. Borum, and D B. Doman

Blockage of the epithelial zonulin receptor decreases intestinal permeability in celiac

patients

Celiac patient Non-celiac control patient

Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 582–588. A Bakshi, S Stephen, M L. Borum

ImmusanT raises $12 million to enable advancement of immunotherapy for celiac

disease

Boston Business Journal (blog)-Dec 22, 2014

Prevention of rickets and Vitamin D Deficiency

Pediatrics Volume 122, Number 5, November 2008Carol L. Wagner and F. R Greer

1. Breastfed and partially breastfed infants should be supplemented with 400 IU/day

2. All non breastfed infants and older childrenand adolescents who are ingesting <1000 ml/day of vitamin D should receive 400 IU/day

3. Serum 25-OH-D concentrations in all pediatric patients should be > 50 nmol/L

The DEXA scan provides a highly accurate measurements of body composition for fat and

bone mass

Standard treatments of dyslipidemias in childhood

1. Diet and exercise

2. Niacin

3. Statins (FDA approved for familial hypercholesterolemia over 8 years of age)

4. Bile acid-binding resins (Questran)

Front. Hum. Neurosci., 23 September. E. C. Radlowski and R. W. Johnson

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular

disease

Journal of Lipid Research Volume 53, 2012. G. Porez

Nuclear receptor

E. Hernandez et al, J Biol Chem. 2007

Hepatocyte couple as a model of bile flow

Frontiers in Bioscience 14, 4904-4920, June 1, 2009

Nuclear receptors an emerging treatment in dyslipidemia

BLO

OD

BLO

OD

Bile NTCP BSEP

CAR-constitutive androstane receptor

FXR-farsenoid X receptor

Milestones in the history total parenteral nutrition (TPN)

1650s First used of IV solution (opium and beer)

1960s First used of TPN and first pediatric death

1970-80 First and last TPN modification

. Glucagon- like-peptide-2 (GLP-2) . Omega-3-fatty acids (fish oil) . Short Chain Fatty Acids(Butyrate)

Emerging changes in total parenteral nutrition (TPN)

Bartholome et al., 2014

Butyrate ameliorates T-cell-dependent experimental colitis

Nature 504, 446–450 (19 December 2013). Yukihiro Furusawa et al

Importance of genes in human development

Diet + Genome= Phenotype

Diet + Genome(Nutrigenomics)= Phenotype

We are what we eat

The human body carries about 100 trillion microorganisms in the intestines

10 times more than the total number of human cells

100 times more genes than the human genome

Diet is the most influential environmental factor associated to Crohn disease

Butyrate

The first supper

The Potato Eaters is an oil painting by Dutch artist Vincent van Gogh painted in April 1885

in Nuenen, Netherlands

The Great Famine

Diet + Genome= Phenotype

Genes Diet

Individual Differences

The rise of the hominids as an adaptive shift in fallback foods: Plant underground storage

organs (USOs)and australopith origins

Journal of Human Evolution. 2005. G. Laden and R. Wrangham