Nutritional programming: The concept

Nutritional programming in utero affects the incidence and severity of disease in the adult.  This hypothesis has established a relationship between nutritional environment during critical windows of development plasticity and offspring disease in adult life.  The nutritional programming concept derives from two prior hypotheses:  the Thrifty Phenotype or Barker Fetal Origins of Disease hypothesis (Barker, 1997) and the extended ‘Predictive Adaptive Response’ (PAR) hypothesis (Gluckman & Hanson, 2004 a, b).

The Thrifty Phenotype hypothesis proposed that in utero undernourishment results in permanent detrimental changes leading to the development of diseases later in life. The effects of maternal under-nutrition on fetal development has been studied extensively both in humans and experimental animals.  The initial evidence was based on epidemiological studies of survivors of the Dutch famine of 1944–1945, where perinatal exposure to famine conditions resulted in higher prevalence of overweight in adult offspring.  Subsequent studies showed that perinatal nutritional deficiencies predispose adult offspring to metabolic syndrome, including obesity, cardiovascular disease (CVD), hypertension, and type 2 diabetes.

The Predictive Adaptive Response (PAR) hypothesis proposes that the fetus makes adaptations based on the predicted postnatal environment.  The prenatal nutritional environment is the primary source of ‘prediction’ of the environment available to the fetus per this hypothesis.  When the PAR is appropriate, the phenotype is normal; however, when there is a mismatch between the nutritional environment, either high or low, during critical developmental periods and the adult environment, disease will develop.  PARs can only be induced during critical windows of development. Thus, the windows of potential induction differ for different organs, resulting in extension of the plasticity phase from in-utero to post-natal development.  Furthermore, PAR also extended Bakers hypothesis to nutritional mismatch both to under-nutrition and over-nutrition during critical developmental periods.

Whether adaptive or predictive, developmental programming postulates long-term detrimental effects on adult health due to nutritional imprinting during critical developmental periods. Understanding and mapping the interaction between nutrient imbalance and modification of gene expression have an enormous potential for improving the health of future generations.

What is the direction?

Nutritional programming research requires the multi-disciplinary approach of nutritional genomics in relying on the concepts and technologies of genetics, molecular biology, epidemiology, public health and clinical trials. Model systems based on rodents and mammalians are indispensable, and provide valuable insights into molecular mechanisms underlying nutritional programming. Additionally, more studies are required to reach a better understanding of the precise type, timing and duration of inappropriate nutrition that result in chronic disease outcome. Significantly less data exists regarding longer effects of nutritional programming, especially in human studies.   

Although the original field of nutritional programming focused mainly on metabolic syndrome related diseases, as reflected in changes in body size, focus on detrimental effect of unbalanced nutrition on chronic diseases should be widened to studies of different tissues and diseases. Finally, extension of studies of nutritional programming in the pre-conception period should be further investigated.

Specific areas of interest

·         Studies of the mechanism and nutrient-gene interactions through which nutritional programming influences various tissues.

 

·         Narrowing and defining critical periods in fetal and early post-natal life that affect specific chronic diseases.

 

·         Identify and study the impact of genetic determinants on early programming effects and on subsequent outcome.

 

·         Quantify the effects of early programming on later chronic diseases.

 

·         Specifying the role of specific nutrients and their interactions in the maternal and infant diet on programming effects on disease and their risk factors.

 

·         Studies of epigenetic mechanisms in early-life programming.

Nutritional Programming.doc Nutritional Programming

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