Nutrition: Articles of Note @PharmaceuticalIntelligence.com
Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN
Nutrition and Wellbeing
Introduction
Larry H. Bernstein, MD, FCAP
The chapters that follow are divided into three parts, but they are also a summary of 25 years of work with nutritional support research and involvement with nutritional support teams in Connecticut and New York, attendance and presentations at the American Association for Clinical Chemistry and the American Society for Parenteral and Enteral Nutrition, and long term collaborations with the surgeons Walter Pleban and Prof. Stanley Dudrick, and Prof. Yves Ingenbleek at the Laboratory of Nutrition, Department of Pharmacy, University Louis Pasteur, Strasbourg, Fr. They are presented in the order: malnutrition in childhood; cancer, inflammation, and nutrition; and vegetarian diet and nutrition role in alternative medicines. These are not unrelated as they embrace the role of nutrition throughout the lifespan, the environmental impact of geo-ecological conditions on nutritional wellbeing and human development, and the impact of metabolism and metabolomics on the outcomes of human disease in relationship to severe inflammatory disorders, chronic disease, and cancer. Finally, the discussion emphasizes the negative impact of a vegan diet on long term health, and it reviews the importance of protein sources during phases of the life cycle.
Malnutrition in Childhood
Protein Energy Malnutrition and Early Child Development
Curator: Larry H. Bernstein, MD, FCAP
The Significant Burden of Childhood Malnutrition and Stunting
Curator: Larry H. Bernstein, MD, FCAP
Is Malnutrition the Cost of Civilization?
Curation: Larry H. Bernstein, MD, FCAP
Malnutrition in India, High Newborn Death Rate and Stunting of Children Age Under Five Years
Curator: Larry H Bernstein, MD, FCAP
Under Nutrition Early in Life may lead to Obesity
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Cancer, Inflammation and Nutrition
A Second Look at the Transthyretin Nutrition Inflammatory Conundrum
Author and Curator: Larry H. Bernstein, MD, FACP
Writer and Curator: Larry H. Bernstein, MD, FCAP
The history and creators of total parenteral nutrition
Curator: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
Curator: Larry H Bernstein, MD, FCAP
Vegetarian Diet and Nutrition Role in Alternative Medicines
Curator: Larry H. Bernstein, MD, FCAP
Reviewer and Curator: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
Metabolomics: its Applications in Food and Nutrition Research
Reporter and Curator: Sudipta Saha, Ph.D.
Summary
Larry H. Bernstein, MD, FCAP
The interest in human malnutrition became a major healthcare issue in the 1980’s with the publication of several seminal papers on hospital malnutrition. However, the basis for protein-energy malnutrition that focused on the distinction between kwashiorkor and marasmus was first identified in seminal papers by Ingenbleek and others:
Ingenbleek Y. La malnutrition protein-calorique chez l’enfant en bas age. Repercussions sur la function thyroidienne et les protein vectrices du serum. PhD Thesis. Acco Press. 1997. Univ Louvain.
Ingenbleek Y, Carpentier YA. A prognostic inflammatory and nutrition index scoring critically ill patients. Internat J Vit Nutr Res 1985; 55:91-101.
Ingenbleek Y, Young VR. Transthyretin (prealbumin) in health and disease. Nutritional implications. Ann Rev Nutr 1994; 14:495-533.
Ingenbleek Y, Hardillier E, Jung L. Subclinical protein malnutrition is a determinant of hyperhomocysteinemia. Nutrition 2002; 18:40-46.
It was these early papers that transfixed my attention, and drove me to establish early the transthyretin test by immunodiffusion and later by automated immunoassay at Bridgeport Hospital.
Among the important studies often referred to with respect to hospital malnutrition are:
- Hill GL, Blackett RL, Pickford I, Burkinshaw L, Young GA, Warren JV. Malnutrition in surgical patients: An unrecognised problem. Lancet.1977; 310:689–692. [PubMed]
- Bistrian BR, Blackburn GL, Vitale J, Cochrane D, Naylor J. Prevalence of malnutrition in general medical patients. JAMA. 1976; 235:1567–1570. [PubMed]
- Butterworth CE. The skeleton in the hospital closet. Nutrition Today.1974; 9:4–8.
- Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic nutritional index in gastrointestinal surgery. Am. J. Surg. 1980; 139:160–167.[PubMed]
- Dempsey DT, Mullen JL, Buzby GP. The link between nutritional status and clinical outcomes: can nutritional intervention modify it? Am. J. Clin. Nutr. 1988; 47:352–356. [PubMed]
- Detsky AS, Mclaughlin JR, Baker JP, Johnston N, Whittaker S, Mendleson RA, Jeejeebhoy KN. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987; 11:8–13. [PubMed]
- Scrimshaw NS, DanGiovanni JP. Synergism of nutrition, infection and immunity, an overview. J. Nutr. 1997; 133:S316–S321.
- Chandra RK. Nutrition and the immune system: an introduction. Am. J. Clin. Nutr. 1997; 66:460S–463S. [PubMed]
- Hill GL. Body composition reserach: Implications for the practice of clinical nutrition. JPEN J. Parenter. Enteral Nutr. 1992; 16:197. [PubMed]
- Smith PE, Smith AE. High-quality nutritional interventions reduce costs.Healthc. Financ. Manage. 1997; 5:66–69. [PubMed]
- Gallagher-Allred CR, Voss AC, Finn SC, McCamish MA. Malnutrition and clinical outcomes. J. Am. Diet. Assoc. 1996; 96:361–366. [PubMed]
- Ferguson M. Uncovering the skeleton in the hoapital closet. What next? Aust. J. Nutr. Diet. 2001; 58:83–84.
- Waitzberg DL, Caiaffa WT, Correia MITD. Hospital malnutrition: The Brazilian national survey (IBRANUTRI): a study of 4000 patients. Nutrition.2001; 17:573–580. [PubMed]
The work on hospital (and nursing home) treatment of malnutrition described in this series led to established standards. It first requires identifying a patient at malnutrition risk to be identified via either screening or assessment. This needs to be done on admission, and it has been made mandatory by health care accrediting bodies. In order to achieve this, dietitians need to have the confidence and knowledge to detect malnutrition, which is ideally done using a validated assessment for patient outcomes and financial benefits to be realized.
There is a worldwide relationship between ecological conditions, religious practices, soil conditions, availability of animal food sources, and altitude and river flows has not received the attention that evidence requires. We have seen that the emphasis on the Hindu tradition of not eating beef or having dairy is possibly problematic in the Ganges River basin. There may be other meat sources, but it is questionable that sufficient animal protein is available for the large population. The additional problem of water pollution is an aggravating situation. However, it is this region that is one of the most affected by stunting of children. We have a situation here and in other poor societies where veganism is present, and there is also voluntary veganism in western societies. This is not a practice that leads to any beneficial effect, and it has been shown to lead to a hyperhomocystenemia with the associated risk of arterial vascular disease. For those who voluntarily choose veganism, this is an unexpected result.
Met is implicated in a large spectrum of metabolic and enzyme activities and participates in the conformation of a large number of molecules of survival importance. Due to the fact that plant products are relatively Met-deficient, vegan subjects are more exposed than omnivorous to develop hyperhomocysteinemia – related disorders. Dietary protein restriction may promote supranormal Hcy concentrations which appears as the dark side of adaptive attempts developed by the malnourished and/or stressed body to preserve Met homeostasis. Summing up, we assume that the low TTR concentrations reported in the blood and CSF of AD or MID patients result in impairment of their normal scavenging capacity and in the excessive accumulation of Hcy in body fluids, hence causing direct harmful damage to the brain and cardiac vasculature.
The content of these discussions has also included nutrition and cancer. This is perhaps least well understood. Reasons for such an association may well include chronic exposure to radiation damage, or persistent focal chronic inflammatory conditions. These would result in a cirumferential and repeated cycle of injury and repair combined with an underlying hypoxia. I have already established a fundamental relationship between inflammation, the cytokine storm, the decreased hepatic synthesis of essential plasma proteins, such as, albumin, transferrin, retinol-binding protein, and transthyretin, and the surge of steroid hormones. This results in an imbalance in the protein and free protein equilibrium of essential vitamins, the retinoids, and other circulating ligands transported. This is discussed in the ‘nutrition-inflammatory conundrum”. As stated, whatever the nutritional status and the disease condition, the actual transthyretin (TTR) plasma level is determined by opposing influences between anabolic and catabolic alterations. Rising TTR values indicate that synthetic processes prevail over tissue breakdown with a nitrogen balance (NB) turning positive as a result of efficient nutritional support and / or anti-inflammatory therapy. Declining TTR values are associated with an effect of maladjusted dietetic management and / or further worsening of the morbid condition.
Inflammatory disorders of any cause are initiated by activated leukocytes releasing a shower of cytokines working as autocrine, paracrine and endocrine molecules. Cytokines regulate the overproduction of acute-phase proteins (APPs), notably that of CRP, 1-acid glycoprotein (AGP), fibrinogen, haptoglobin, 1-antitrypsin and antichymotrypsin. APPs contribute in several ways to defense and repair mechanisms, being characterized by proper kinetic and functional properties. Interleukin-6 (IL-6) is regarded as a key mediator governing both the acute and chronic inflammatory processes, as documented by data recorded on burn, sepsis and AIDS patients. IL-6-NF possesses a high degree of homology with C/EBP-NF1 and competes for the same DNA response element of the IL-6 gene. IL-6-NF is not expressed under normal circumstances, explaining why APP concentrations are kept at baseline levels. In stressful conditions, IL-6-NF causes a dramatic surge in APP values with a concomitant suppressed synthesis of TTR.
Inadequate nutritional management, multiple injuries, occurrence of severe sepsis and metabolic complications result in persistent proteolysis and subnormal TTR concentrations. The evolutionary patterns of urinary N output and of TTR thus appear as mirror images of each other, which supports the view that TTR might well reflect the depletion of TBN in both acute and chronic disease processes. Even in the most complex stressful conditions, the synthesis of visceral proteins is submitted to opposing anabolic or catabolic influences yielding ultimately TTR as an end-product reflecting the prevailing tendency. Whatever the nutritional and/or inflammatory causal factors, the actual TTR plasma level and its course in process of time indicates the exhaustion or restoration of the body N resources, hence its likely (in)ability to assume defense and repair mechanisms.
In westernized societies, elderly persons constitute a growing population group. A substantial proportion of them may develop a syndrome of frailty characterized by weight loss, clumsy gait, impaired memory and sensorial aptitudes, poor physical, mental and social activities, depressive trends. Hallmarks of frailty combine progressive depletion of both structural and metabolic N compartments. Sarcopenia and limitation of muscle strength are naturally involutive events of normal ageing which may nevertheless be accelerated by cytokine-induced underlying inflammatory disorders. Depletion of visceral resources is substantiated by the shrinking of FFM and its partial replacement by FM, mainly in abdominal organs, and by the down-regulation of indices of growth and protein status. Due to reduced tissue reserves and diminished efficiency of immune and repair mechanisms, any stressful condition affecting old age may trigger more severe clinical impact whereas healing processes require longer duration with erratical setbacks. As a result, protein malnutrition is a common finding in most elderly patients with significantly increased morbidity and mortality rates.
TTR has proved to be a useful marker of nutritional alterations with prognostic implications in large bowel cancer, bronchopulmonary carcinoid tumor, ovarian carcinoma and squamous carcinoma of bladder. Many oncologists have observed a rapid TTR fall 2 or 3 months prior to the patient’s death. In cancer patients submitted to surgical intervention, most postoperative complications occurred in subjects with preoperative TTR 180 mg/L. Two independent studies came to the same conclusion that a TTR threshold of 100 mg/L is indicative of extremely weak survival likelihood and that these terminally ill patients better deserve palliative care rather than aggressive therapeutic strategies.
Thyroid hormones and retinoids indeed function in concert through the mediation of common heterodimeric motifs bound to DNA response elements. The data also imply that the provision of thyroid molecules within the CSF works as a relatively stable secretory process, poorly sensitive to extracerebral influences as opposed to the delivery of retinoid molecules whose plasma concentrations are highly dependent on nutritional and/or inflammatory alterations. This last statement is documented by mice experiments and clinical investigations showing that the level of TTR production by the liver operates as a limiting factor for retinol transport. Defective TTR synthesis determines the occurrence of secondary hyporetinolemia which nevertheless results from entirely different kinetic mechanisms in the two quoted studies.
Points to consider:
Protein energy malnutrition has an unlikely causal relationship to carcinogenesis. Perhaps the opposite is true. However, cancer has a relationship to protein energy malnutrition without any doubt. PEM is the consequence of cachexia, whether caused by dietary insufficiency, inflammatory or cancer.
Protein energy malnutrition leads to hyperhomocysteinemia, and by that means, the relationship of dietary insufficiency of methionine has a relationship to heart disease. This is the significant link between veganism and cardiovascular disease, whether voluntary or by unavailability of adequate source.
The last portion of these chapters deals with metabolomics and functional nutrition. This is an emerging and important area of academic interest. There is a significant relationship between these emerging studies and pathways to understanding natural products medicinal chemistry.
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