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Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods...

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Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring Course 2015
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Page 1: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring Course 2015

Page 2: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Objectives

  Provide a scientific review of the health effects of GMO

  Identify food sources of GMO

  Discuss controversies

  Examine recommendations regarding diet

Page 3: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Disclosures

  Nothing to Disclose

Page 4: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Highly Politicized Topic   Anxiety about unknown

vs. risk to human health

Page 5: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Concerns   Environmental

  Threat to biodiversity   Ecological impact   Animal rights   Destruction of non target

organisms

  Philosophical   Playing God   Integrity of the order of species   Fear of unknown   Few companies have large market

share and control

  Human health Allergenicity

  Toxicity   Pesticide use   Gene transfer   Stability of gene   Nutritional effects

Page 6: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Benefits

  Food availability

  Resistance to pesticide, viruses, diseases

  Weed/drought/freeze resistance

  Prolonged shelf life

  Crop yield

  Lower price

  Decrease pesticide use

  Improved nutritional value

Page 7: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Revolution in Biotechnology

  Meet challenge of population growth

  Consistent food supply

  Counter world hunger

  Political stability

Page 8: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

What is GMO?

  Genetically modified organism   DNA has been altered (plants or animals)

  Not “naturally” (mating or recombination)

  Allows genes to be transferred between organisms

  AKA gene technology, genetic engineering

Page 9: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Plant breeding Unconscious! deliberate saving of seeds

  Domestication   Selection of favorable traits

Mendelian genetics

  Evolving science

Page 10: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Selective Breeding

  Overlap and similarities but:   Faster

  Can introduce a gene that is not naturally occuring

  Can occur between different species (eg. Human to bacteria)

  Methods of DNA transfer   DNA microinjection

  Retrovirus mediated gene transfer

  Stem Cell mediated gene transfer

Page 11: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Worldwide GMO use   United States 42% acreage

  88% of corn

  93% of soy

  94% of cotton

  75% of papaya

  90% canola

  54% sugar

  Worldwide 12%   Brazil 17%

  Argentina 16%

  India 6%

  Canada 6%

  Europe <1%

Crops also used for animal feed

Page 12: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Traits

  1st generation   Resistance to herbicides, pests, diseases, viruses

  2nd generation   Increased protein, healthier fats, improved

flavor

  3rd generation   Drought and freeze resistance

  Other   Drugs, biofuels, bioluminescence

Page 13: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Most Common Traits   Resistance toward herbicides- HT (80%)

Glyphosate resistant (Roundup Ready)   Inhibitor of 5-enolpyruvylshikimate-3phosphate synthase (EPSPS)

  Amino acid pathway

  Replaced with gene of EPSPS from bacteria CP4 EPSPS

  Resistance toward insect damage   Bacillus thuringiensis (Bt)

  Natural toxin: Cry endotoxin, VIP

  Used in organic farming

  Short lived

  Inserts into insect gut and damages

Page 14: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

GMO Health Effects   >4000 studies

  Overwhelming support for safety of GMO

  Environment

  Many animal species

  Many types of GMO

  Drawbacks   Short term studies: 30-90 days

  Gross measures   Mortality

  Weight gain

  Macroscopic evaluation

  Paucity of human studies

Page 15: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

National/International Organizations Endorse GMO

  Safe for human consumption

  WHO

  FDA

  USDA

  EPA

  National Academy of Sciences

  CDC

  European Food Safety Authority

  New food

  These are for population or areas of food insecurity

  Standard is “substantial equivalence”

  Is lack of evidence confirming danger confirmation of safety?

  Many conventional crops have toxicities

Page 16: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Potential Health Effects

Allergenicity

  Toxicity

  Gene Transfer

  Herbicide use

Page 17: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Allergenicity

Nordlee, Taylor et al. NEJM, 1996   2s albumin from Brazil nut transgenically added to soybean.   3 subjects with Brazil nut allergy exposed with skin prick from

soybean extracts and conventional soy   All 3 had reactions to brazil nut, GM soy and negative for soy

  Immune blotting 8/9 subjects IgE bound to Brazil nut and GM soybeans

Transfer of allergenic property can occur through genetic modification

Page 18: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Allergenicity   2001 StarLink corn- Bt meant for animal feed made its way

into human food supply with Cry9c- potential allergen   Found in taco shells   Extensive media coverage

  CDC investigated   Case definition and used questionnaires to ID 28 subjects in

15 states through AERS   Secured serum samples and tested for IgE reactivity to Cry9c

and compared to banked 1996 pre StarLink blood   All were non-reactive

  No allergic reactions to GM foods on the market   Most common food allergens are not GMO

  milk, eggs, peanuts, tree nuts, fish, shellfish, soy, and wheat   Still on shelves

Page 19: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Toxicity on Intestines

  Research Letter Lancet, Pustzai et al. 1999   Rats fed GM potatoes vs conventional

  Evaluated rat intestines

  Groups of 6 rats fed for 10 days   Raw/boiled: GM potatoes, conventional potatoes,

conventional potatoes with GM protein supplemented

  Rats fed GM potatoes   Raw: increase proliferation of jejunum

  Boiled:   Hyperplasia of stomach

  Decreased proliferation of cecum

Page 20: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Toxicity   168 pigs 1:1 randomization GM soy/corn or non GM diet

  22.7 weeks slaughtered and eval by blinded vet

  No difference on feeding, weight gain, organ weights, mortality, blood markers

  GM pigs   Uteri 25% heavier

  Higher rate of severe stomach inflammation 32% v 12% p=0.004

Carman et al, Journal of Organic Systems 2013

Abnormal hearts: GM pigs 6%; control group 15%

GM Conventional

Page 21: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Toxicity- Long Term

  10 rats randomized to diet to GM maize vs. conventional maize for 2 years   Females developed large mammary tumors

94 days before controls

  Liver abnormalities 2.5-5.5 times more common than controls

  Pituitary tumors more common in GM group

  Mortality 25% in controls; 60% in GM

  Unlimited access to food/ food intake not reported

Seralini et al 2014

Study was eventually retracted by the journal

Page 22: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Long Term Toxicity   Review of 12 long term and 12 multigenerational studies 90 days to

2 years   No signs of toxicity overall   Sheep: changes in liver nuclei   Mice

  B cell compartment expanded lymphoid tissue in GM wheat   Different expression of liver proteins in HT Soy   Microscopic pancreas changes in HT Soy

Hisological differences in liver in HT Soy   Rats

  Bt maize minor histological changes in liver and kidney   Salmon: mid intestine smaller in HT Soybean

  Relevance of differences in unknown   Natural variation   Non GM (control groups) no isogenic lines used   Indicate need for further study

Snell et al, 2012

Page 23: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Gene Transfer

  Transfer a novel trait to a new organism that may be harmful

  Silence genes

  Change gene expression

  Develop toxic compound

  Mutagenesis

  Absorption into systemic circulation or milk

  Humans consume 0.1-1 g/day of DNA

Page 24: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Antibiotic Resistance

  Transfer of new gene to plant is inefficient   5 in 1000 cells

  To determine which cells have taken up gene a marker is used   Antibiotic resistance is one such marker   Cells are treated with antibiotic   Only cells with transferred gene survive

  Factors are considered   Antibiotic importance   Resistance patterns in soil and gut flora

Kanamycin resistance   Not used: ampicillin resistance, amikacin resistance

Page 25: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Gene transfer

  Phipps et al. 2005

  GM corn fed to 60 lactating dairy cows for 12 weeks

  Weekly samples obtained   No transgenic DNA detected in milk

  No difference in milk yield or composition

  Study in chickens showed no DNA made it to small intestines

Page 26: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Oral Gene Transfer

Schubbert 1997   DS DNA given orally to 6 m/6 f mice

  Fragments of DNA were recovered, small intestine, large intestine, feces and blood of mice in decreasing amounts

  0.05% DNA in circulation

  Likely transferred through intestinal wall   Unknown mechanism

  Intestinal tract is not an absolute barrier for absorption of DNA

Page 27: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Human study

  7 ileostomy patients and 12 control fasted   Baseline stool sample then fed GM soy burgers and GM

soy milk shake and marker

  Stool samples for 72 hours collected

  3 ileostomy subjects showed evidence of prexisting gene in stool

  No transgene in controls

  0.1 to 3.7% of transgene

recovered in case

Netherwood et al, Nature Biotech 2004

Page 28: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Gene transfer   Very low likelihood event

  Horizontal gene transfer is orders of magnitude lower than vertical gene transfer: 1 in 1012

  Even transfer to bacteria occurs spread is small

  10% of gut bacteria has some antibiotic resistance

  We eat antibiotic resistance from soil (e.g. kanamycin)

  No evidence that gene transfer to flora or into mammalian DNA occurs

  No laboratory evidence of gene transfer from eukaryote to bacteria

  Occurs in traditional breeding   More consistency in transgenic crops

Page 29: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Herbicide Use   80% of GM crops are HT

  Decreased herbicide use…initially

  Increase in glyphosate use   Based on ecological studies

  Fewer alternative herbicides

Bonny S, 2001 Sustainability

Is increasing glyphosate use a concern?

Page 30: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Glyphosate toxicity

  Inhibits EPSPS enzyme in plants   Low oral, dermal, inhalation acute toxicity

  Chronic toxicity   NOEL 362 mg/kg   Minimal dermal/inhalation absorption in occupationally

exposed   Rapidly excreted from human body   Uptake by plant leaves: half life 9 days   Does not bioaccumulate in animals, eggs, milk: half life 3

hours   Not lipid soluble

Page 31: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Glyphosate and Cancer

  EPA   Not carcinogenic

  IARC 2015: 2A: probable carcinogen   Most studies show no genotoxicity

  In vitro lymphocytes: sister chromatid exchange and chromosomal aberrations (Lioi et al, 1998)

  Agricultural Health Study (AHS) (DeRoos et al, 2005)

  57311 pesticide applicators followed for approx 7 years   Self reported exposure

  No link with 13 different cancers

  4 case control studies found a link between glyphosate and NHL

Page 32: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Glyphosate Toxicity

  Not absorbed by plant roots   But by leaves and stems

  Increased concentrations with late harvest applications   Human exposure >500 fold less than Oral reference

dose set by EPA

  Generally considered safer than other herbicides

  Likely does not impact human health

Page 33: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

What now?

  Paucity of Human data   Over 20 years of human use

  Most animal studies suggest safety   What about the microscopic changes?

Page 34: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Future Research   Factor GMO

  Set to begin worlds largest study on GMO

  Secret location

  Transparent funding

  25 million dollars

  Thousands of rats over 2-3 years

  Multigenerational

  Safety of GMO and associated pesticides   Long term toxicity

  Carcinogenicity

  Fertility or birth defects

Page 35: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Human data

  >7400 patients over 5 years randomized to specific diets

Page 36: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Prevention   Eat a variety of foods

  FDA recommends

  Corn, papaya, squash

  Avoid processed foods

  Cooked foods are safer   95 degrees degrades DNA

  GMO foods are not labeled   Eat organic

  100% or USDA certified

  Buy Non GMO certified

Page 37: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Areas of Concern   Use of antibiotic resistance markers

  Appropriate use of glyphosate by farmers

  Compositional changes to GMO should undergo evaluation   Develop improved techniques for toxicologic evaluation   Microarrays, proteomics, metabolomics

  Monitor allergenicity   Identify and track those at risk   Standardize methods for reporting food allergies

  Post-marketing surveillance for unanticipated adverse events   Continuing Survey of Food Intakes by Individuals and the National

Health and Nutrition Examination Survey (NHANES)

  Indirect health concerns from environmental effects

Page 38: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Conclusion

  GMO are ubiquitous revolutionary technology with potential

  Overall meets standard of substantial equivalence

  No reason to suspect adverse health events

  No health adverse health effects documented from GMO

  As toxicologists, we should monitor and be aware of the ongoing studies pertaining to this

Page 39: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

Questions

Page 40: Food Toxicology: Genetically Modified Foods and …...Food Toxicology: Genetically Modified Foods and Human Health Josef G. Thundiyil, MD, MPH, FACEP, FACMT Orlando Health ACMT Spring

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