American Society of Parenteral and Enteral Nutrition

             

   Fiber,Insulin Resistance &Cardiovascular Disease

   David J.A.Jenkins,MD,PhD,DSc

   Fiber can be divided into 2 groups,insoluble and soluble fibers.The soluble fiber is viscous and includes pectins,gums and B -glucans (oats and barley).One of the benefits of soluble fiber (viscous) is that it can hypothetically slow carbohydrate absorption by holding materials in the gastrointestinaI (GI) tract,which results in a different hormonal response and maybe a lower glycemic index and insulin response.When fiber is added to meals of patients with Diabetes Mellitus (DM),the fiber appears to reduce plasma blood glucose (BG) with peaks being much less extreme.Cereal fiber and glycemic load (GL) are both associated with risk of type II DM.Less cereal fiber intake and the higher GL appears to be associated with the highest risk.A meta-analysis comparing a low vs high glycemic index diet showed a mean 8% decrease in glycated proteins in the low glycemic index diet.C reactive protein seems to increase with higher GL.Helsinki,Paris and Busselton have demonstrated that increased insulin levels are an independent risk factor for coronary heart disease (CHD).The Nurses study showed that individuals with a BMI >23,have increased risk for CHD with increasing GL.Acarbose therapy decreased the relative risk of hypertension (HTN) by 34% and cardiovascular disease (CVD) events by 49%.Bread consumption alone has a trend towards higher risk of breast cancer and colon cancer with higher intakes.When a low GL diet was compared to an energy-restricted reduced-fat diet in obese adolescent teenagers,only the low glycemic index diet sustained a lower BMI for 12 months.A low glycemic index diet appears to be protective of chronic disease by slowing absorption,of which part of is carbohydrate absorption.

   Nutrition Support in Cancer

   Leah Gramlich,MD

   It has been reported that up to 20% of cancer patients die from malnutrition.Many factors can contribute to the anorexia-hospitalfood seen in cancer patients.The type of cancer will influence the degree of weight (wt) loss experienced by patients.Reduced intake,adverse effects of medication,adverse effects of therapy and GI obstruction all contribute to poor intake.Increased energy loss can occur due to tumor burden,rate of tumor growth,malabsorption and sepsis.The combination of these factors lead to nonvolitional wt loss that contributes to morbidity and mortality.Nutrition support (NS) can be used in patients at high nutritional risk (>10% wt loss).The goals of NS in advanced cancer are to minimize wt loss,improve tolerance to antineoplastic therapies,promote immune function,reduce complications related to malnutrition and improve quality of life (QOL).

   There may be a role for immunonutrition in cancer patients.In 1999,Braga et al studied 206 patients with neoplasm of the colon,stomach or pancreas.Use of an immune enhancing diet (IED) was associated with reduction in infection &hospital length of stay.

   Use of home parenteral nutrition (HPN) in advanced cancer patients has been controversial.Individual assessment is required.This therapy is most appropriate for those with unusable GI tract,high QOL and reasonable life expectancy.

    Protein Nutrition for Patients with Advanced Cancer

   Vickie E.Baracos,PhD

   Cancer-associated hospitalfood is a progressive wasting condition that appears to parallel the progression of cancer.Recently the focus has been on skeletal muscle mass/ lean body mass (LBM) and the amino acids (AA) required to support maintenance and gain of LBM.When pts lose LBM,other functions such as wound healing are also affected.AA are the building blocks for protein and can determine protein synthesis.

   The right hormone makeup is also needed to open the synthesis process.Currently there are no citations in the literature of empirical determination of requirements for any AA in cancer patients.There is some information from experimental studies and theoretical considerations.

Process AA

Protein synthesis All

ATP production Glutamine

Nucleotide synthesis Glutamine

Polyamine synthesis Arginine

Ornithine

Nitric oxide synthesis Arginine

Methyl group transfer Methionine

Serotonin synthesis Tryptophan

(endocrine tumor)

   Several researchers have tried to determine if AA supplementation promotes tumor growth.So far there are no comprehensive answers to this question.In animal studies on glutamine supplementation,95% of articles show no effect on tumor growth and 5% of the articles show decreased tumor growth.These results occurred even with high doses of AA.In animal studies using arginine supplementation,50% of articles show no effect on tumor growth or inhibition of tumor growth.The other 50% of articles suggest increased tumor growth.One human study showed increased tumor protein synthesis.

   Many are also questioning if AA supplementation alters pharmacokinetics or efficacy of chemotherapy drugs.

   The total and relative amounts of essential AA required are altered in malignancy.Glutamine,arginine,and cystine may normally be considered nonessential for humans but can become conditionally essential in patients with cancer.Whole body utilization of glutamine,arginine,cysteine/methionine and glutathione,and branched chain AA are all increased.

   It may be possible to manipulate AA supplies in the tumor bearing state in a manner that favors the host overall.The identification and supplementation of limiting AA in cancer patients has the potential of altering muscle loss,lean mass and function,anti-oxidant status (glutathione),improve immunity,improve tolerance to treatments,and improve morbidity/mortality.

   Many patients with cancer have intakes of 19-28 Kcals/kg and 0.8-1.1 gm/Kg protein but they require 35-40 Kcals/kg and 1.4-1.6 gm/Kg of protein to maintain LBM.Therapies have focused on appetite stimulants,anabolic steroids and dietary protein supplementation to improve intake.Currently,there are several options for pharmacological management of anorexia in advanced cancer patients.Metoclopramide,domperadine,and cisapride can be used to control nausea.Corticosteroids (dexamethasone) cause temporary increase in appetite of up to 4 weeks.Side effects include infection,poor glycemic control and loss of muscle mass.Progestational agents (egestrol acetate) lasts longer than corticosteroids.Side effects include impotence,thromboembolic episodes and loss of muscle mass.Agents intended to stimulate the appetite may also inhibit protein deposition and cause wasting of the skeletal muscle.

   Principal elements of muscle anabolism therapy are steroids (oxandrolone,nandrolone),purified AA mixtures/dietary protein sources,creatine,and resistance exercise.Research is just now starting to evaluate if cancer patients have any anabolic potential.Von Roenn et al tested oxandrolone in patients with locally recurrent or metastatic malignancy (colorectal and lung).They reported patients responsive to oxandrolone gained 11 lbs of which 8 lbs was LBM.May et al reported reversal of cancer-related wasting using oral supplementation with a combination of b-hydroxy-b -methlbutyrate,arginine and glutamine.An ongoing multicenter,randomized double-blind trial by MacDonald et al is evaluating whey protein isolate versus casein in the prevention of wasting in the treatment of colorectal or non-small cell lung cancer.

   Some classes of chemotherapy have been associated with a significant decrease in n-3 fatty acids in plasma phospholipid.Fearon et al reported a significant relationship between plasma phopholipid eicosapentaenoic acid (EPA) levels and change in LBM in patients consuming a protein and calorie dense oral supplement with n-3 fatty acids.Pratt at al demonstrated that EPA levels in plasma phospholipids are related to the change in body wt during fish oil supplementation in patients with advanced cancer.N-3 fatty acid availability may need to be optimized to maximize anabolic competency.

   Optimizing What is Delivered:Dosing,Formula,Additives

   Stephen A.McClave,MD

   Adequate NS can be defined as the provision of nutrients in such a manner that optimal patient outcome is achieved.In the past,nutritionists have purported the concept that a small amount of “trophic feeds” or “trickle feeds” (i.e.,10-30 ml/hr) provided a sufficient volume of enteral nutrition (EN) to maintain gut integrity.In a rat model with injury,over 50% of goal calories were required to effectively reduce translocation and maintain gut integrity.Demeo demonstrated similar findings in bone marrow transplant patients.Several studies are now suggesting that “sufficient” volume of EN may provide a greater attenuation of stress response and resolution of disease severity.Also,the therapeutic effect from IEDs may only be achievable with a sufficient volume of formula provided.Ziegler et al.reported that a decreasing enteral score (kcals provided/energy requirement) correlated significantly to an increasing sepsis score.It appears that a small volume of “trickle feeds” or “trophic feeds” is insufficient to achieve the desired endpoint and that a volume closer to 60% of goal feeding may be required to achieve the therapeutic benefit of EN.Bartlett showed that patients who remained in a positive energy balance had a mortality of 26.6%.Patients who sustained a 10,000-calorie negative energy deficit however,had a significantly increased mortality of 76.4%.Mault and Villet each found worse outcomes in patients with cumulative energy deficit.

   The composition of the formula becomes an important issue in certain patient populations who may benefit from a specialty IED.In comparison to standard enteral formulas,use of an IED impacts patients outcome,reducing length of hospitalization,length of stay (LOS) in the ICU,incidence of nosocomial infection,multiple organ failure,and in some circumstances in specific populations even mortality.Over 18 prospective randomized controlled trials and 3 meta-analyses suggest that patients undergoing major elective surgical procedures (esophagectomy,gastrectomy and pancreatectomy),burns,head injury,and non-septic critically ill patients are likely to benefit from use of an IED.Critically ill patients who are already septic at initial presentation may actually do worse with the use of IED and should instead be placed on standard formulas.

   Little data exists to suggest an impact on patient outcome from use of other specialty formulas.While sound physiologic principles support the makeup and design of certain specialty formulas for specific populations with pulmonary disease,liver disease,renal failure,stress,and DM,increased expense and lack of data to support impact on patient outcome preclude their use.

   Diarrhea often leads to an increase in nursing demands and possibility of other complications such as volume depletion and skin breakdown.Prospective studies have shown that more than 50% of cases of diarrhea associated with EN are actually caused by medications such as magnesium-containing antacids and sorbitol-based elixirs.In 15-20% of cases,diarrhea is antibiotic-associated related to the overgrowth of Clostridia difficile .Only in <20% of cases is diarrhea caused by a malassimilation of the enteral formula.True malassimilation of a standard enteral formula may necessitate switching to one or two alternatives,either a peptide formula with fat primarily in the form of MCTs to enhance small bowel absorption,and/or a formula with a bulking agent in the form of fiber to reduce stool frequency.

   Gastric Versus Small Bowel Feedings.Will the Right Organ Please Stand Up?

   Mark H.DeLegge,MD

   Early EN has been demonstrated to improve wound healing,preserve intestinal mucosal integrity,improve host immune function,and decrease hospital LOS.The opportune time to begin EN following hospital admission remains a point of much debate.In general,it is believed that initiation of tube feeding (TF) within 24-36 hours of admission will help obtain positive patient outcomes.

   Although gastric access is easier to obtain than small bowel (SB) access,there is still significant concern about the use of gastric feeding and the risk of regurgitation and aspiration,especially in the critically ill.A meta-analysis by Heyland et al reported a reduction in ventilator-associated pneumonias with SB feeding as compared to gastric feedings.In a similar study by Neumann et al there was no difference in aspiration pneumonia with the 2 types of feeding.

   Many ICU pts have gastroparesis,potentially limiting the success of gastric feeding.In addition,many medications commonly used in the ICU,such as morphine,reduce gastric motility.In these circumstances,SB motility is usually still intact allowing feeding to be initiated in the SB.Placement of SB feeding tubes is usually more technically difficult than gastric feeding tubes.

   If a patient has a history of gastric intolerance or lacks the anatomy to receive gastric access,SB feeding is initiated.In most other circumstances,gastric feedings are initiated and the patient is monitored for gastric intolerance.If gastric intolerance occurs,SB access is obtained and feeding initiated.

   A meta-analysis by Marik et al was very helpful in attempting to evaluate the benefits of gastric versus SB TF.It appears that EN is initiated sooner in the gastric fed patients than the SB fed patients.Patients fed into the SB were able to catch up and had a similar mean caloric intake.The delay in feeding did not seem to impact outcomes.The relative risk for pneumonia in the gastric fed group was 1.44 that of the jejunal fed group.Interestingly,the gastric fed group had a 1.4-day reduction in LOS.

   Studies have shown that gastric residual volumes (GRV) do not correlate to gastric emptying or to the volume of gastric contents.Unfortunately,inappropriately low threshold volumes for GRV trigger feeding cessation,decreasing overall feeding infusion time and calories delivered.In a study evaluating the factors that impede EN delivery,elevated GRV was the most common reason.

   What Supports Adjusted Weight in Nutrition Support

   Joe Kenitsky,MS,RD

   Carol Ireton-Jones,PhD,RD,LD,CNSD

   Methods for predicting energy requirements in obese patients vary widely and are often inaccurate.The most commonly used equation is the Harris-Benedict equation (HBE).Actual body weight (ActBW) in the HBE tends to over estimate energy requirements in obese subjects and can lead to complications of overfeeding.Ideal Body weight (IBW) tends to under-predict energy requirements for obese subjects.An adjusted body weight (ABW) has been proposed to overcome the errors of the other approaches.The most common ABW calculation is:

   IBW+(Act BW x 0.25).There are other ABW calculations where 0.25 is replaced with 0.32 to 0.5.Clinicians have used ABW in the HBE and other formulas such as Kcal/kg

   Barak et al did a retrospective study of 567 hospitalized patients and evaluated the best ABW calculations.ABW with 50% correction (average of actual and ideal wt) adjusted better than 25% or 33% correction factor in patients with BMI >30.

   Many other equations have been developed but few have proven to accurately predict energy requirements of obese subjects.Cutts,Amato and Glynn all compared energy equations and measured resting energy expenditure (REE) in obese patients.The patients varied in their stress levels.In general,the results showed increased individual variability with increased BMI and therefore all the equations perform worse with rising BMI.

   Frankenfield et al did a prospective study of 130 healthy adult volunteers.47 of the patients had BMI >30.They compared measured REE with several equations.The Mifflin-St.Jeor equation performed the best for normal wt and obese subjects.They reported that ActBW with HBE resulted in an over-prediction of needs in 30% of patients.Adjusted body wt using a 25% correction factor under-predicted REE.

   Predicting individual hospitalized obese patients energy needs is very difficult because of different degrees of obesity,different percentages of LBM,and different stress responses.Measuring metabolically active tissue is the most logical approach to estimating energy needs but fat free mass cannot be easily and accurately measured.Another consideration is that measured energy expenditure can change as much as 46% from day to day.Most of the studies evaluating these equations used only one indirect calorimetry measurement.

   Debating the accuracy of predictive equations may not be important when it is unclear if hypocaloric,eucaloric or hypercaloric feeding in the ICU is best.Some preliminary reports show that there is not a dramatic difference in outcome between groups fed 50 and 90% of REE in the ICU.There are several good studies to show that hypocaloric feeding is not detrimental in the critically ill obese pt.Another important consideration is that many ICU pts do not receive the volume of NS as ordered.If administration is less than exact,is it important for estimated needs be exact? Following evidenced based protocols,education and monitoring of the protocols is probably the best way to improve outcomes from feeding in the ICU.

   In summary,no equation is accurate in predicting the resting metabolic rate of obese,hospitalized patients.Of the available equations,the Mifflin-St.Jeor equation appears to perform the best in normal and obese subjects.Over-feeding can be detrimental so it is best to avoid predictive equations that over-estimate needs such as the HBE with ActBW.ABW used in predictive equations is based on theory and appears not to improve accuracy of predictions in obese patients;however,it may help in avoiding overfeeding.When available indirect calorimetry appears to be the best method for determining energy needs in the obese population.

Frailty

   John E.Morley,MD,BCh

   Only recently has the term "frail"been defined with specific criteria.Fried and colleagues suggested that if a person has 3 or more of the following factors,they can be considered frail.

• Un-intentional weight loss

• Self-reported exhaustion

• Weakness as measured by grip strength

• Slow walking speed

• Low physical activity

   Women are more likely to be frail than men.Identifying the frail can help to predict falls,deteriorating mobility,disability,hospitalization and death.Frailty is associated with CVD,low education and low income.

   The management of frailty is derived from the pathogenesis.The Geriatric Depression Scale should be done on all frail persons and if depressed they should be treated.Resistance exercise is the cornerstone of the management of frailty.Ideally all frail elderly should undergo resistance training 3 sessions/week.Balance exercises should also be incorporated to help maintain balance and prevent falls.All males should have bio available testosterone measured and low testosterone replaced.The use of testosterone in women is controversial.Growth hormone replacement has not been demonstrated to increase strength,but it does increase muscle mass and produce nitrogen retention.

   Poor intake can be treated with caloric supplements between meals.Orexigenic agents such as dranabinol may increase appetite.Those with hyperhomocystinemia should be checked for hypothyroidism.Some may benefit from folate,vitamin B 12,and vitamin B 6 in pharmacological doses.Peripheral vascular disease should be treated with phosphodiesterase inhibitors and aerobic and resistance exercises.Early cognitive impairment may respond to cholinesterases inhibitors.Cytokine excess can be assumed with an elevated C-reactive protein (CRP).Megesterol acetate reduces cytokines and should be considered as a treatment option.

   Frailty is a defined complex condition in the elderly and treatment options should include nutrition and exercise as major components.Early identification and treatment of frailty can improve outcomes.

   Aging,Nutrition,Immune,and clinical outcomes

   Bobbi Langkamp-Henken PhD,RD

   The elderly population is rapidly growing and this is expected to put high demands on the healthcare system.Elderly tend to have a lower immune response,which can be further harmed by poor nutritional status.Hudgen et al compared whole blood T-cell proliferation,neutrophil burst and delayed hypersensitivity (DTH) in well and malnourished nursing home elders.The well-nourished subjects had significantly better immune response.

   If malnutrition is contributing to illness in the elderly,then possibly nutritional supplementation can help to improve immune function and decrease illness in the elderly.Langkamp-Henken et al evaluated arginine supplementation in nursing home elders with pressure ulcers and found that arginine was well tolerated,but had no affect on IL-2 production and may have decreased induced lymphocyte proliferation.A follow up study evaluated immune function with arginine supplementation and found no effect on immune function.

   Vitamin E supplementation has been of interest in the elderly because it is an antioxidant and it is known to decrease PGE 2 and increase IL-2.Meydani et al set out to determine if 1 year of vitamin E supplementation affected respiratory tract infection in nursing home elders.They reported a decrease in all respiratory tract infections but interestingly,no difference in antibiotic use.They also noted that 11% of the subjects were deficient in carotenoids and about 50% were deficient in zinc.A multinutrient supplement may be the best approach for elderly who can have multiple nutrient deficiencies.

   Langkamp-Henken et al evaluated the effect on upper respiratory tract infections (URTI) of an experimental formula containing energy,protein,structured lipid,vitamins,mineral and antioxidants in the elderly.The supplement was provided prior to and 6 months post vaccination for influenza vaccine.The treatment group had decreased days of URTI,increase in antibody response to

   influenza vaccine,increased in proliferative response to viral antigens and the product was orally and metabolically well tolerated.This study demonstrates that there is promise that the use of nutrients may improve the health of our growing elderly population.

   Nutritional Considerations in the Geriatric Patient

   Gordon Sax PharmD,BCNSP,FCCP

   Geriatric patients have unique considerations due to changes with aging.Calorie requirements are reduced due to a decrease in energy expenditure.Providing 20-25 Kcal/Kg/d is appropriate for most elderly.Protein needs for the unstressed geriatric patient can be met with 0.8 to 1 gm/Kg/d,those with severe stress may need up to 1.5 g/Kg/d.

   Several micronutrient alterations are more common in the elderly.Vitamin B 12 status can be low due to atrophic gastritis.Lack of sun exposure and impaired cutaneous synthesis can lower vitamin D levels.Elevated vitamin A in plasma and hepatic stores can occur in the elderly,partially due to a decrease in renal degradation.

   Recommendations due to these issues are:

   -vitamin B 12 may need to be increase in patients with gastritis;

   -vitamin D may need to be increased from the RDI of 5 mcg/d (200 IU) to 10 mcg/d (400 IU) in homebound or institutionalized elderly;

   -individuals taking vitamin supplements may be at risk for vitamin A toxicity.Chronic vitaminosis A may lead to liver abnormalites and bone changes such as bone mineral loss and possibly spine/hip fractures.

   Dehydration is the most common fluid/electrolyte disorder in the elderly in long term care facilities and community dwelling.There are several formulas available for estimating fluid requirements of the elderly:

• 25-30 ml/Kg (25 for congestive heart failure)

• 30-25 ml/Kg with a minimum of 1500 mL

• 1 ml/Kcal intake

• ((Wt(kg)-20) X 15)+1500 mL

   Risk factors for dehydration include deterioration in cognitive status or abilities,failure to eat or take medication,urinary track infection within the last 30 days,fever,vomiting or diarrhea,weight loss (>5% over 30d or >10% over 180d),leaving >25% of food uneaten at most meals,use of laxative or diuretics,uncontrolled DM and swallowing problems.

   Diagnosis of dehydration can be confirmed with laboratory tests.Skin turgor,dry mucous membranes,in/out charts and urine specific gravity are unreliable markers for dehydration.The oral route should be used for treatment of dehydration unless the patients is hemodynamically unstable,has intractable vomiting,unresponsive or gastric distention.There are several oral rehydration fluids and infusates available.“Free water” can be replaced orally but it should never be given IV or as sterile water for injection.

   Scientific Abstract

   Peptide based diet with low amount of free amino acids enhances gastrointestinal structure and function in young pigs with compromised gastrointestinal tract.

   Maples BA,Chung BM,Tappenden KA.

   This study was designed on the hypothesis that a peptide-based diet with a low amount of free AA would enhance intestinal structure and function compared to an intact protein diet or a peptide diet with a higher amount of free AA.Twenty young pigs with intestinal injury,2 weeks after weaning,were randomized to receive via gastrostomy tube,isocaloric,isonitrogenous complete nutrient formulas of either 1) intact protein diet,2) peptide diet with <1% free AA,or 3) peptide diet with 40% free AA for 7 days post surgery.Body wt and formula tolerance did not differ,but there were differences in nutrient absorption and intestinal structure.The results showed that provision of a peptide-based diet low in free AA increases the structure of the proximal small intestine,as demonstrated by increased crypt depth,mucosal and intestinal mass.These structural alterations are associated with enhanced glucose absorption,and AA and peptide absorption,with the effect continuing into the distal GI tract.The authors conclude that based on these results,the feeding of a low free AA peptide diet to children with compromised intestinal function may provide appropriate mucosal stimulation while maintaining feeding tolerance.

   Role of Arginine (arg) in the Immunomodulatory Effects of Crucial O in a rat head injury (HI) model.

   Hamani D,Charrueau C,Butel MJ,Besson V,Nicolis I,Le Plenier S,et al.

   The aim of this study was to define the role of arginine in the immunomodulatory effects of Crucial O in HI rats.Thirty-four male Sprague-Dawley rats were randomized into 5 groups:1) ad libitum (AL),2) HI,3) HI+Sondalis O HP,4) HI+Sondalis O HP+arg (HISA) in the same amount as in Crucial O,and 5) HI+Crucial O (HIC).They were fed isonitrogenous,isocaloric diets over 4 days.The rats were then sacrificed,and the density of CD25 receptors on blood lymphocytes was evaluated at basal state and after stimulation with Concanavalin A (ConA),and production of IL2 was measured by ELISA.

   The results showed that in response to ConA stimulation,CD25 density and IL2 secretion were significantly increased only in HISA and HIC rats.Only Crucial counteracted thymus atrophy induced by HI.HI induced bacterial dissemination was blunted only in the HISA group.

   The authors concluded that this study shows that arginine contributes to a large extent to the immunomodulatory effects of Crucial O,and seems to limit bacterial dissemination.

   The next Clinical Nutrition Week will be held February 5-8,2006 in New Orleans,LA,USA.Further information may be found at http://www.nutritionweek.org/