GENETIC NUTRITION: GENE MUTATIONS CAN PRODUCE......

The following abstract, along with a preview of his paper on "Epigenetics, Genomics, etc.", was presented by Prof. Herbert, at Prof. Simopoulus' request, immediately after her keynote lecture, in session 6.8 "Diet and Genes" at the 17th International Congress of Nutrition (under the auspices of The International Union of Nutritional Sciences, organized by The Austrian Nutrition Society), Austria Convention Center, Vienna, Austria, Aug 27-31, 2001. Both presentations, and the audience questions and answers that followed, were audio-taped by the host Society. Participants in, and co-sponsors of, the Congress, were the University of Vienna; several Austrian Federal Ministries; the International Atomic Energy Agency (IAEA); FAO; the Commission of the European Union; WHO; and UNICEF. Due to serious defects in the host Society's solely electronic communication system, a number of abstracts, including Prof. Herbert's, were not listed in either the Program or Abstracts published (for distribution in August at the Congress) in the journal of the Federation of European Nutrition Societies, Annals of Nutrition & Metabolism 2001; 45 (Suppl 1): 1-636.

GENETIC NUTRITION: GENE MUTATIONS CAN PRODUCE POLYMORPHISMS (ALLELES) WHICH ALTER MINIMAL DAILY REQUIREMENTS (MDRs) FOR ESSENTIAL MINERAL AND VITAMIN MICRONUTRIENTS SUCH AS IRON, VITAMIN B₁₂, AND FOLIC ACID.

Prof. Victor Herbert, M.D., J.D., M.A.C.P., F.R.S.M.(London), Mount Sinai-New York University & Bronx V.A. Medical Centers, NY City, USA.

Genetic polymorphisms affecting a protein involved in micronutrient absorption, transport, delivery, or utilization, can alter the polymorphís MDR for that nutrient (Simopoulos A, Herbert V, Jacobson B: Genetic Nutrition: New York: Macmillan, 1994 [republished 1995 as The Healing Diet]; Herbert V. Clin Investig Med, Feb, 2001). Examples of gene mutations altering micronutrient absorption are the genetic polymorphisms which produce hemochromatosis (genetic iron overload). They so sharply enhance the intestinal absorption of dietary iron above the ìnormalî ~10%, by weakening the complex ìmucosal blockî biochemical machinery for inhibition of iron absorption, that the MDR for iron to sustain normal iron metabolism falls sharply. Those with one such gene (heterozygotes) absorb daily ~50% more dietary iron than normal, those with 2 (homozygotes) absorb daily ~300% more dietary iron. An example of a gene mutation altering a protein involved in both the transport and delivery of a micronutrient is genetic deficiency of the circulating vitamin B₁₂-delivery protein transcobalamin, producing severe global vitamin B₁₂ deficiency disease in infancy which, if not recognized in infancy and treated from then on with adequately large amounts of vitamin B₁₂, is lethal. Examples of gene mutations affecting micronutrient utilization are the gene mutations producing alterations (polymorphisms) in the folate-utilizing enzyme methylenetetrahydrofolate reductase (MTHFR) which reduce its specific activity. A MTHFR polymorph with slowed ability (specific activity) to convert methylene THF to methyl THF retards the conversion by methyl THF of potentially vasculotoxic and neurotoxic homocysteine to methionine. As with many sluggish ìtraffic copî enzymes, the slowed conversion is speeded by increasing the supply of substrate (in this case, increasing the folate minimal daily requirement (MDR) to overcome the problem). The MDR for folic acid as PGA (pteroylglutamic acid) is normally only 25 micrograms. A daily oral intake of 250 to 400 micrograms of PGA corrects for sluggish MTHFR.