To eat or not to eat? Nutrigenomics and the DRI
Simon J Stern1, Neil D Dattani, BHSc2, *
1 Biological
and Medical Sciences Program, University of Western Ontario
of Medicine Program, University of Toronto
2Doctor
*neil.dattani@utoronto.ca
ABSTRACT
This paper outlines the shortcomings of current scientific nutritional recommendations,
and elucidates the need for better recommendations. The field of nutrigenomics is
explained and presented as a possible solution to these problems. Evidence which
indicates the promise of nutrigenomics in solving these problems is also presented.
Potential limitations to the expansion of nutrigenomics are identified.
Dietary Reference Intakes (DRIs) are “quantitative approximations of nutrient
intakes for the purpose of planning and assessing the diets of healthy people”
(Gropper). DRIs reflect scientific knowledge of nutrient requirements, and are
established using studies done in Canada and the U.S.A.(Gropper). While they
definitely have their purposes, one of the major limitations of DRI’s is that they are
created for the general healthy population, and thus cannot cater to specific
populations. For example, post-menopausal women require a higher daily intake (about
1,200 mg/day) of calcium than the recommended average for the general public (about
1000 mg/day) (http://ods.od.nih.gov/factsheets/calcium.asp). Even factors such as
geographic location and the time of year are now known to impact nutritional
requirements (Debusk), and these are not accounted for by DRIs.
Current DRIs have their origins in the ‘recommended dietary allowance’ (RDA)
guidelines. These guidelines have existed for over 70 years and were developed during
the Second World War to aid America’s war effort by ensuring the population was as
healthy as possible. (Harper) Several key scientists, including Lydia J Roberts and
Hazel Stiebeling, were assigned the task of determining a standard recommended daily
intake for important nutrients (Harper). For decades before the RDA, sailors and
servicemen had carefully monitored diets to prevent such conditions as scurvy or
malnourishment (Harper), however the work done by Roberts and Stiebeling provided
dietary recommendations for ordinary civilians. Over the years the RDA was refined into
the DRI and important adjustments were made to model the average American’s
lifestyle.
Today, we look at the concept of the DRI in a new light. Genetics has begot
genomics, and genomics has begot nutrigenomics; a field that redefines the DRI to the
scale of the individual.
Extensive research has shown that genes have a significant role in nutrition and
metabolism (Debusk) and (Vernarelli), and several studies have shed light onto
previously unknown associations. A chief objective of nutrigenomics is to determine
specific requirements for nutrients, and to see how variables such as an individual’s
genes and environment can change these requirements from day to day (Debusk).
Indeed, nutrigenomics has begun to play an important role in determining
appropriate nutrient intake levels in people with polymorphisms in certain genes. For
example, variations in the IL1A, IL1B, and IL1RN genes may result in a higher risk of
developing cardiovascular disease (Gropper). Among other things, an individual with
such variations would require a greater intake of anti-atherosclerotic polyunsaturated
fatty acids than the DRI in order to obtain a level that is protective against heart disease
(Gropper).
Another gene related to cardiovascular morbidity which affects nutrient
requirements is the LIPC gene, which codes for hepatic lipase (Gropper). This enzyme
is involved in the binding and uptake of lipoproteins, and when overexpressed, HDLcholesterol concentrations decrease (Gropper). Conversely, when hepatic lipase is
underexpressed, as is the case in individuals homozygous for a variant allele of the
LIPC gene, –514(C/T), HDL-cholesterol concentrations are increased (Gropper). HDL
scavenges cholesterol from circulation and thereby reduces the formation of
atherosclerotic plaque (Gropper), thus it is in important to control the amount of this
lipoprotein in one’s diet. Clearly, individuals with different LIPC alleles have different
requirements for HDL.
It has also been shown that the relationships between nutrients and genes can
affect multiple physiological systems simultaneously. A recent study done by Garrod et
al. looked at the association between vitamin B12 and its carrier protein,
transcobalamin. It was found that a variant form of transcobalamin has a lower binding
affinity for vitamin B12 than the normal form of this protein. The researchers determined
the exact nucleotide at fault (position 776 C>G transversion) as well as the amino acid
substitution that occurred (proline to arginine) (Garrod). Thus, individuals with the
776GG genotype have less bioavailable vitamin B12 in their plasma than those without
this variation. Recognizing and understanding their increased requirements for vitamin
B12 will help curb the incidence of neurological diseases, gastrointestinal diseases, and
megaloblastic anemia in these people.
The immense complexity and scale of the interactions involved in the field of
nutrigenomics is a central issue precluding the progress of an all systems-based
approach to nutrition. There are a myriad of genes which effect metabolism and
countless mutations which can modify these interactions (Gropper). It has been
proposed that the best way forward is not to try to solve the whole system per se, but
rather to identify the key players (Müller). To that end, studies are commonly conducted
which evaluate the effect of single genes/proteins on nutrition (Müller).
Regardless of its focus, research is showing to an increasing extent the
importance of diet modifications in individuals with recognized genetic risk factors for
nutritional deficiencies. With hope, such research will one day lead to a revolution in the
way nutritional recommendations are made. An important aspect of this revolution to
consider will be the response of patients – whether they will respond to the changes
they need to make based specifically on their genetic codes. An interesting study was
carried out to determine how willing patients would be to follow new dietary
recommendations after it was revealed they were carriers for a specific allele, APOE ɛ4
(Vernarelli). This allele is known to increase the risk of developing Alzheimer’s disease,
while nutritional and lifestyle changes are believed to lessen the risk of developing this
disease (Vernarelli). The study initially examined the proportion of first-degree relatives
of patients of Alzheimer’s disease, who were willing to improve their nutritional intake,
and this proportion was determined to be only 16% (Vernarelli). However, when the
patient population was analyzed according to whether or not they had at least one copy
of APOE ɛ4, it was found that those with the allele were almost five times more likely to
improve their nutritional habits than those without (Vernarelli). This demonstrates the
need for better implementation of nutrigenomics in healthcare.
With the increased prevalence of chronic diseases and severe morbidity in
populations around the world, we must do what we can to improve human health.
However, there are barriers to overcome. In addition to those already identified, a
significant barrier to the expanded use of nutrigenomics is the cost involved. Major
financial limitations in healthcare systems around the world may in fact be the biggest
obstacles preventing the utilization of some of the most promising recent advances in
nutritional research.
The work has been done, the need is clear, and the time is right. Now all that
remains to be seen is whether nutrigenomics will overcome the obstacles, and prove to
be the nutritional breakthrough we have been waiting for.
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