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Nutritional Genomics As It Relates to Detoxification

Nutritional Genomics As It Relates to Detoxification

By Dr. Patrick Lovegrove Medically Reviewed by Lindsay Langley, BSN, RN, CHT
Posted Thursday, January 17th, 2019
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Nutrigenomics is the influence of nutrients on gene expression and provides a genetic understanding of how common dietary components affect the balance between health and illness

The study of nutrient-gene (nutrigenomics) interactions is becoming a popular and developing area of science, and people now accept that the diet-genome relationship affects our health. In other words, nutrigenomics the belief that there is an optimal individualized diet that, if compromised, could expose a person to greater health risks is gaining credibility. As the poet, Lucretius stated long ago, “What is food to one man is bitter poison to others.”  But why is that? Because the nutrients from food can interact with molecular mechanisms and modulate biochemical functions in the body.

Nutrigenomics is the influence of nutrients on gene expression and provides a genetic understanding of how common dietary components affect the balance between health and illness by altering the structure or expression of an individual’s genetic makeup. On the other spectrum, nutrigenetics is the interplay between gene variants and dietary components, which also play a role in the development of nutraceuticals. Genetic variations have a known impact on the extent to which food intolerances may influence dietary requirements, and they open the door to optimal health through personalized nutrition.

Genetic polymorphisms can influence responses to environmental factors such as enzymatic changes that, in turn, influence the effectiveness of chemicals and metabolites. Therefore, metabolic conditions may influence genetic variations in diets such as Phenylketonuria (PKU), defects associated with iron absorption (hemochromatosis), and long-chain fatty acid oxidation. These conditions may be reasonably well-managed with dietary restrictions.

Single nucleotide polymorphisms (SNPs) may be a potential molecular tool for evaluating the role of nutrition in human health and illness, and the identification of appropriate diets. Nutrients may serve to repress or induce gene expression thus altering an individual’s phenotype. SNPs may alter the bioactivity of important mediators and metabolic pathways to influence the ability of nutrients to interact with these pathways.

The complex interaction between SNPs, enzyme deficiency and nutrients have been reviewed in recent research. Mutations in the phenylalanine hydroxylase gene, glucose-6-phosphate dehydrogenize (G6PD) and galactose-1-phosphate uridyltransferase (GALT) gene resulted in Phenylketonuria (PKU), Favism disease, and Galactosemia respectively. Another example of enzyme polymorphisms includes the Lactase-phlorizin hydrolase gene (LPH) associated with hypolactasia and changes in tolerance to dietary lactose (sugar in milk).

Detox Pathways

Research shows that certain polymorphisms and nutrients may influence detoxification pathways. Food-based nutrition has been and continues to be explored for its role in the modulation of metabolic pathways involved in detoxification pathways. Several clinical studies to date demonstrate that food-based components and nutrients may influence processes of conversion and excretion of toxins out of the body. In general, these findings may indicate that specific foods may upregulate or favorably balance metabolic pathways to assist with detoxification.

Although genes are crucial for regulating function, nutrition modifies the extent to which different genes are expressed and, thereby, modulates whether individuals obtain the potential benefits of their genetic background. The following is a list of enzymes commonly associated with detoxification pathways, which may be influenced by both genetics and nutrition.

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a vital role in the detoxification of reactive oxygen species. A change in the genome, substituting valine with alanine in this enzyme, may prevent its transport into the mitochondria, which has been associated with increased breast cancer risk.

CYP1A2 plays a vital role in metabolizing a wide range of chemicals and drug substances. CYP1A2 activates dietary carcinogens such as aromatic amines but detoxifies compounds such as caffeine. Individuals with low expression of the CYP1A2 genotype generally metabolize caffeine slower and are at a greater risk of caffeine-associated heart disease. As caffeine is the main compound in coffee and certain teas and is detoxified by CYP1A2, it may be a crucial risk factor for heart disease in certain populations.

UDP-Glucuronosyltransferases are essential in enhancing the elimination of toxins in feces and urine, as well as metabolizing bilirubin and steroid hormones. UDP polymorphisms are associated with hereditary unconjugated hyperbilirubinemias: Crigler-Najjar syndrome type I, type II, and Gilbert syndrome. Clinical studies reported that bioactive compounds, cruciferous vegetables, citrus, and resveratrol induce UGT enzymes. Phytochemicals may modulate, rather than induce enzymatic activity with many studies reporting that effects are variable depending on genotype and gender. Women with the UGT1A1 28 polymorphism responded to citrus intervention, whereas those with other genetic variants were not affected.

Glutathione S transferases (GST) main function is the conjugation of the sulfur group on glutathione (GSH) to produce a water-soluble compound excreted via bile or urine. They play an important role in antioxidant defense and detoxification. Foods such as alliums, cruciferous vegetables, and resveratrol have been shown to induce GSTs in humans. Interestingly, genetic variances, body weight, and gender may play a role in the dietary factors on GST enzymes.

N-Acetyl Transferases (NAT) are involved in the metabolism of carcinogens and drugs, where polymorphisms in genes for this category of enzymes have been shown to lead to poor metabolism, hepatoxicity during drug treatment, and certain cancers.

Sulfotransferases (SULT) play a role in the detoxification of procarcinogens and toxins. Decreased function of these enzymes and polymorphisms may be a predisposing factor for lung cancer. Sulfur-containing compounds from dietary sources may play an essential role in SULT function by providing a substrate for the action of the enzyme.

Methylene-tetra-hydro-folate reductase gene (MTHFR) is a well-known example of gene-nutrient interaction in nutrigenetics. This is a required enzyme for the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This conversion is necessary for the multi-step process that converts homocysteine, an amino acid, to methionine, another amino acid. MTHFR is needed to metabolize folic acid and maintenance of the normal levels of homocysteine in the blood.

The polymorphisms C677T and A1298C are associated with elevated homocysteine levels in the blood, especially when the diet is deficient in folic acid. Individuals with low expression of the MTHFR enzyme may present with birth defects, heart disease, and the inability to detoxify. Nutrient deficiencies such as B2, B6, B12, and folate are associated with elevated homocysteine levels.

Although nutrigenomics is an evolving science with much to learn and discover certain dietary messages remain clear and consistent; a whole foods-based diet, replete with phytonutrients and antioxidants, always seems in vogue.

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About the author

Dr. Patrick Lovegrove

Dr. Patrick Lovegrove is board certified by the American Board of Family Physicians. He was born in Staunton, Virginia, and graduated from the University of Virginia where he majored in Biology. He received a Medical School Scholarship from the United States Air Force. A graduate of Nova Southeastern College of Osteopathic Medicine, his over 20 years of clinical experience includes Family Practice, Anti-aging, Holistic Internal Medicine, Pain Management, Aerospace, Sports, and Emergency Medicine. He believes that holistic medicine should be integrated with conventional medicine in a scientifically based model to achieve the best results for patients.