Physiologic and Pathophysiologic Factors Affecting Micronutrient Requirements

The dietary requirements of micronutrients for any individual are affected by a number of physiological and pathological factors such as bioavailability of given micronutrient, amount, age and gender

Physiological factors such as aging have specific impact on the requirements of some micronutrients due to the reduced energy requirements, food intake, absorption, metabolism and utilization and that can cause deficiency of certain micronutrients. Atrophic gastritis, is highly prevalent in elderly population and this can lead to impaired absorption of protein bound vitamin B12.2 As compared to younger adults in RDA, greater requirements are set for Vitamin B6, Calcium and Vitamin D3 to address PEM, anaemia, decreased absorption of calcium, osteoporosis in elderly. Deficiency of Vitamin D3 has been found to have association with multiple diseases like hypertension, dyslipidaemia, insulin resistance, obesity, diabetes, metabolic syndrome3, Alzheimer’s disease4 and certain cancers.5

The ingestion, digestion and absorption of nutrients take place in the gastrointestinal tract. For the transformation of nutrients liver is of prime importance and pancreas is essential to digestion and metabolism. So it is very common that GI, hepatic and pancreatic diseases have significant nutritional impact, and they can cause multiple nutritional deficiencies.

Why micronutrient deficiency in GI diseases?

Lack of availability, reduced intake, malabsorption6 and maldigestion are the major causes of micronutrient deficiencies globally. Patients having gastrointestinal diseases are significantly predisposed to deficiencies of nutrients be it macro or micronutrients, as they may have multiple factors e.g. reduced food intake, dysphagia, malabsorption, maldigestion, as well as excessive GI losses of fluid and nutrients. And all these can lead to specific deficiencies including micronutrient deficiencies.7 Reduced intake may be secondary to anorexia, nausea and/or vomiting, severe diarrhoea, dysphagia or odynophagia, abdominal pain, obstruction, iatrogenic factors, restrictive, non-nutritious diets with dietary manipulation. Maldigestion and malabsorption can be the consequent to mucosal disease, decreased absorptive surface area, pancreatic insufficiency, bile salt insufficiency, bacterial overgrowth, drug induced e.g. corticosteroids (calcium), sulfasalazine/methotrexate (folate), cholestyramine (fat and fat soluble vitamins). Gastrointestinal losses involve diarrhoea and bleeding, fistulae, protein-losing enteropathy. There may be increased nutritional requirements during active catabolism, active inflammation, fever, corticosteroid usage.8

Gastrointestinal diseases that affect sites (small intestine, pancreas, and/or hepato-billiary tree) or the mechanisms of nutrient absorption in the GI tract leads to specific nutritional deficiencies. GI diseases such as Inadequate bowel - short gut syndrome, Crohn's disease, Celiac disease, Gastrectomy with Bilroth-II anastomosis, Bariatric surgery, Chronic pancreatitis, Chronic liver disease and cholestatic liver disease may have long term nutritional consequences.8

Major micro nutritional deficiencies associated with a variety of GI disorders are nutritional anaemias (iron, folate, B-12), Vitamin deficiencies (A, thiamine, riboflavin, niacin, pyridoxine, D, K) Trace element deficiencies ((iron, copper, selenium, zinc). Trace element toxicity (manganese). Bone disease (decreased bone mineral density and osteomalacia)8.

Majority of micronutrients including both fat and water-soluble ones except vitamin B12 are predominantly absorbed in proximal small intestine. Therefore, diffuse mucosal diseases affecting proximal small intestine can cause multiple nutritional deficiencies. Even though in the absence of proximal small intestinal diseases, some pathologies such as extensive ileal disease, chronic cholestasis or small intestinal bacterial overgrowth (SIBO) may affect the optimum intraluminal conjugated bile acid concentration leading to impaired absorption of fat soluble vitamins. Conditions like cystic fibrosis or congenital biliary atresia often have overt fat malabsorption, yet having well recognized fat soluble vitamin deficiencies. Conditions like later stages of cholestatic liver disease have subtler fat malabsorption. 23, 24, Chronic pancreatic insufficiency cause fat malabsorption leading to maldigestion and fat soluble vitamin deficiencies. Early stages of many micronutrient deficiencies are undetectable and often goes undiagnosed and their progression can sometime lead to increased morbidity and be disastrous as in conditions like irreversible spinocerebellar degeneration due to fat soluble vitamin E deficiency. 23

Why micronutrient guidelines in GI diseases?

Almost all the micronutrients being absorbed in GI tract, patients with gastrointestinal disorders are at highest risk of having multiple nutritional deficiencies including micronutrient deficiencies. Malnutrition and deficiencies can be prevented or treated by optimal medical nutrition therapy, yet limited specific knowledge about micronutrients remains among clinicians. Further knowledge on trace elements remains miniscule as compared to vitamins. Practical recommendations based on available micronutrient guidelines are therefore required regarding procedures for determination of requirements 9, especially for GI diseases as this is the commonest encountered problem that can impair enzymatic as well as biochemical processes and lead to multiple complications including death.

General Recommendations

• Micronutrient deficiencies can be suspected and identified firstly based on the dietary recall as well as the NFPE (Nutrion-focused physical examination) followed by screening by laboratory investigations if practical. Assessment of malnutrition and treatment in patients having gastrointestinal diseases is important for positive clinical outcome and to reduce costs.

• Patients may have preexisting malnutrition that can result in further vitamins and trace elements deficiencies when affected by current illness and other treatment related complications. 30

• Anemia and micronutrient deficiencies should be checked by blood tests in patients with gastrointestinal diseases and those with inflammatory bowel disease or malabsorption should be checked for vitamin D deficiency. 31

• Providing adequate amounts of micronutrients is an integral part of medical nutrition therapy.

• Patients with GI diseases are predisposed to malnutrition with depleted micronutrients due to preexisting illness, reduced intake, increased requirements or due to increased losses. 6

• Micronutrient deficiencies may lead to serious nutritional consequences. Inadequate intake of micronutrients may initially be compensated by increased absorption from gut, decreased renal excretion or by decreased growth velocity in case of zinc. When there occur progressive depletion intracellular contents may get reduced with resultant impairment in biochemical functions like reduced intracellular enzymatic activity and may also affect gene expression/regulation. Short term effects like cognitive effects fatigue and impaired immune functions, whereas long term effects such as free radical damage to DNA/cell membrane may occur as non-specific functional effects leading to clinical disease or even death. 33 Therefore adequate intake of micronutrients is crucial for public as well as individual health.

• The current recommendations are for both hospitalized as well as outpatients with gastrointestinal diseases. Majority guidelines on micronutrient provision are primarily for hospitalized or critical patients receiving medical nutrition support. However, the clinician should not forget that some patients especially out patients may be benefited from specific single or multiple oral micronutrient supplements. 9

• Ideal way to provide micronutrients is through gut as absorption of micronutrients by the gut can be adapted to the requirements 25. During the critical illness nutrient absorption can be compromised due to bowel ischemia, edema or ileus, yet even in haemodynamically unstable patients hypo caloric enteral feeding have been found to be unaffected regarding nutrient absorption 34 and micronutrient supplementations are required in very small quantity. However levels can be achieved more confidently with the intravenous administration of micronutrient supplementation. 25

• -Blood levels of micronutrient determined are found to be low as an effect of redistribution of micronutrients from circulation to other organs due to inflammation in the cases like surgery, infection, acute or chronic diseases. 32

• It has been found in healthy individuals undergoing elective surgeries that without any change in whole body micronutrient status, within one day of surgery their plasma concentration of multiple micronutrients were significantly decreased. 35

• Except vitamin B12 micronutrient levels in blood are impacted by inflammation usually when CRP levels exceeds 20mg/dl. Albumin is a negative acute phase protein and affected by dilution during inflammation. Being career for many micronutrients it should be determined too in the settings of inflammation. 35, 9

• To comply with the directives regarding formulation of food for medical nutrition therapy, the complete formula should contain the 100% RDA for micronutrients if it is providing 1500 kcal(35), therefore those who are on complete nutritionally balanced formula feeds may not require supplementation of micronutrients. 26

• Minimum intake suggested for an individual with complete formula feeding is kept 2000kcal/day, which is higher than the energy requirements of normal population to address increased requirements of an individual on enteral feeding. 37, 29

• Commercially available PN solutions contain only lipids, glucose, amino acids and some electrolytes but trace elements and vitamins are excluded in PN solutions because of the stability reasons.so should be prescribed separately, 38 however Unfortunately Micronutrients are not added in majority of the patients on parenteral nutrition. 39

• It is a practice to add multivitamin preparation (including vitamin) and a multiple trace element admixture (containing Zn, Se, Cu, Cr, and Mn) to be added to (PN) formulations. 25 The recommendations for vitamins and trace elements of interest for enteral and parenteral formula in practice and their suggested composition are there. 25

• Blenderised feeds lack in uniform and optimal nutritional composition that is recommended to meet the requirements, as compared to commercial feeds. 40, there for with relation to meet daily micronutrients requirements additional supplementation should be considered.

Disease specific recommendations for major Gastrointestinal Diseases