I eat, therefore I am a nutrition expert

The blog by Dr. Morris on “I eat, therefore I am a nutrition expert” highlights the importance and need of trained experts in nutrition and nutritional epidemiology in order to advance in the fight against neurodegenerative diseases.

In recent years, there have been important advances in Alzheimer's disease at the pre-clinical level. Unfortunately, these advances have not been reflected at the clinical level, where no effective drug in slowing the disease progression has yet been discovered. Likewise, in the past two decades, it has been suggested that Alzheimer's disease should be addressed from a metabolic perspective. This implies that obesity, exercise, and nutrition could be positive or negative contributors to the disease evolution. Following this line of thought, several studies have discussed the neuroprotective effects of some nutrients and dietary components such as vitamin E, green leafy vegetables, and other vitamins [1]. Moreover, some of these nutrients are necessary for an adequate physiological functioning of the brain and for neuronal protection, especially against oxidative stress.

In spite of this, many nutritional research studies have shown inconsistent results, suggesting that these interventions are not adequate for neurodegenerative diseases prevention. These undesirable results may be reinforced by the lack of nutrition experts in neuroscience clinical trials. A good example of a successful collaboration and a multidisciplinary research team is the PREDIMED study. This randomized diet-intervention trial conducted in Spain evaluates the effects of the Mediterranean diet on the human health and brain aging [2]. The Dietary Approaches to Stop Hypertension (DASH) evaluates the effect of diet against many cardiovascular risk factors, some of which also related with cognitive decline, in randomized clinical trials in the United States [3]. These research studies constitute appropriate strategies, uniting different areas of research with nutrition experts, in order to reach a cognitive improvement, which is essential in Alzheimer's disease.

Antoni Camins, Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
Jordi Olloquequi, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile

References
[1] Shah R (2013) The role of nutrition and diet in Alzheimer disease: a systematic review. J Am Med Dir Assoc 14, 398– 402.
[2] Valls-Pedret C, Lamuela-Raventós RM, Medina-Remón A, Quintana M, Corella D, Pintó X, Martínez-González MÁ, Estruch R, Ros E (2012) Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 29, 773-782.
[3] Larsson SC, Wallin A, Wolk A (2016) Dietary approaches to stop hypertension diet and incidence of stroke: results from 2 prospective cohorts. Stroke 47, 986-990.

We applaud the editorial “I eat, therefore I am a nutrition expert,”” by Martha Clare Morris.

We have previously advanced the concern that clinical studies with nutritional interventions have an inherent compromise. Preclinical analyses with nutritional interventions have repeatedly demonstrated cognitive benefit, and have delayed the appearance of multiple Alzheimer-related biomarkers. Clinical studies with nutritional interventions, however, have typically been less successful. Part of this discrepancy is that preclinical studies allow a degree of control over basal diet (current and historical), environment/social interaction, age and genetic background that is virtually impossible to establish in clinical studies.

Clinical nutritional studies are faced with the difficulty of recruiting sufficient numbers of individuals that have low or inadequate baseline nutritional status, such that a cohort with defined initiation of supplementation can be compared to an appropriate placebo cohort not receiving supplementation. An additional wrinkle arises in that while initiation of a nutritional intervention would at first thought be more likely foster improvement for individuals with a history of deficiency in the nutrient in question, these particular individuals may have undergo irreversible damage that may preclude any benefit. Any comprehensive attempt to address the full gamut of possibilities would therefore require cohorts of individuals with prior adequate diet, individuals with adequate diet plus whatever nutritional intervention is under consideration, and individuals with a prior deficient diet. These groups would then be further divided into groups that maintained their historical intake and those that altered their diet from deficient to adequate and vice versa. Finally, all of these cohorts would be independently randomized to receive the supplement or placebo, followed eventually by a crossover phase [1]. The complications inherent in clinical nutritional studies dramatically exceed those of pharmacological interventions, which have the inherent advantage that participants from diverse backgrounds are likely to have de novo exposure to the intervention.

Effectively addressing even some of the above criteria in appropriately-controlled, randomized clinical nutritional studies, and monitoring what is by definition a complex outcome, warrants expertise far beyond that of those of us who can simply supplement the diet of one or more transgenic mice and monitor performance in maze trials or conduct histochemical analyses of a biomarker or two in brain tissue. The onset and progression of dementia is itself a grey area, and the impact of nutritional interventions is likely to extend the grey scale, rather than provide a black and white impact.

Finally, consideration of the amounts of the supplement under investigation, and/or its precursors or metabolites, that may already be in the diet of some individuals, and the impact a one nutritional supplement on bioavailability of other nutrients, further call for nutritional expertise. In this regard, it is particularly noteworthy that combinatorial formulations, rather than individual vitamins or nutraceuticals, have displayed maximal impact [2].

To carry the call for appropriate expertise raised by Dr. Morris one step further, we consider it essential that a clinical research team contain nurses and/or Physician’s Assistants for cognitive test administration and discussions with family members in order to optimize sensitivity and comfort of participants that is lost in the absence of one’s personal physician or neurologist.

Thomas B. Shea
Laboratory for Neuroscience
UMass Lowell
Lowell, MA 01854

Ruth Remington
Framingham State University
Framingham, MA 07102

REFERENCES
[1] Shea TB, Rogers E, Remington R (2012) Nutrition and dementia: Are we asking the right questions? J Alzheimers Dis 30, 27-33.
[2] Shea TB, Remington R (2015) Nutritional supplementation for Alzheimer’s disease. Curr Opin Psychiatry 28, 141-147.