MicronutrientsMicronutrientsKhursheedKhursheed

JeejeebhoyJeejeebhoy

ElectrolytesElectrolytes RudmanRudman

et al. J et al. J ClinClin

Invest 55:94Invest 55:94--104, 1975104, 1975

Patients on TPN were studied twice:Patients on TPN were studied twice:1. With full Na, K, P, N supplements1. With full Na, K, P, N supplements2. After removing each singly2. After removing each singly

Elemental balances were calculated.Elemental balances were calculated.

ElementNormal Increased GI

lossesRenal Failure Comments

Potassium 40-80 mmol 80-120 mmol 0-20 mmol Correcthypokalemiabefore startingnutrition

Magnesium 5-10 mmol 10-20 mmol 0-5 mmol see comment forpotassium

Phosphorus 10-15 mmol 10-15 mmol 0-5 mmol lipid porvidesphosphorus

Zinc 3-4 mg(TPN)

15-20 mg(Enteral)

12- 25mg (TPN)50-100 mg(enteral)

no change losses are largelythrough the GItract

Requirements for Anabolic Minerals

Micronutrients and Micronutrients and EnteralEnteral

feedingfeeding

EnteralEnteral

feeds only meet the RDA if:feeds only meet the RDA if:Minimal volume is fedMinimal volume is fedMinimal volume depends on product.Minimal volume depends on product.

Deficiency of multiple Deficiency of multiple micornutrientsmicornutrients occurs if less volume is fed. (J occurs if less volume is fed. (J PedPed

GastGast

NutrNutr

2001;33(5)6022001;33(5)602--605605

Micronutrients and Micronutrients and EnteralEnteral

feedingfeeding J J PedPed

GastGast

NutrNutr

2003:33:6022003:33:602--55

Scurvy: Gum hypertrophy

Zinc Deficiency

Subperiosteal

hemorrhage

Trace element supplementation major burns: RTC

M.Berger

et al:Am J Clin Nutr 1998;68:365–71.

20 patients with 4520 patients with 45+ 10 % BSA+ 10 % BSA10 control and 10 TE (supplemented)10 control and 10 TE (supplemented)Supplements received IVSupplements received IVProteinProtein--Energy fed Energy fed enterallyenterally..

Trace element intakeTrace element intake All sources over 8 days.All sources over 8 days.

ELEMENT CNTR TESELEMENT CNTR TESZinc (Zinc (umolsumols) 2681 4683) 2681 4683Copper (Copper (umolsumols) 451 579) 451 579Selenium (Selenium (umolsumols) 11.2 30.1) 11.2 30.1

IRONIRON

Constituent of Constituent of porphyrinporphyrin--based:based:HemoglobinHemoglobinMyoglobinMyoglobin

Storage: Storage: FerritinFerritin

and and HemosiderinHemosiderinTransport: Transport: TransferrinTransferrin

IRONIRON

Loss: Normal 0.6 mgLoss: Normal 0.6 mg--1.0 mg/day1.0 mg/dayMenstrual: 1.1 to 1.8 mg/dayMenstrual: 1.1 to 1.8 mg/day

Absorption:Absorption:HemeHeme excellentexcellentGastric acid releases Fe from proteinGastric acid releases Fe from proteinAscorbic and organic acids Ascorbic and organic acids inceaseinceasePhosphate and Phosphate and PhytatesPhytates reducereduce

IRONIRON

Requirements:Requirements:TPN about 2 mg/dTPN about 2 mg/d

EnteralEnteral, often difficult to add enough in feeds , often difficult to add enough in feeds to meet requirements without intolerance.to meet requirements without intolerance.

IronIron--sucrose can be infused in doses of 250 sucrose can be infused in doses of 250 mg/ 100 mg/ 100 mLmL infused over 1 hour without any infused over 1 hour without any reaction. (reaction. (NephrolNephrol Dial TransplantDial Transplant.. 2001 Jun;16(6):12392001 Jun;16(6):1239--4444).).

ZINC PROTOCOLWOLMAN ET AL GASTROENTEROLOGY 1978

TPN INTAKE

DAY 1 21

ZINC INTAKE

O OR 6 1.5 0R 12 3 0R 23 mg / d

24 HOUR URINE AND STOOL COLLECTIONS

Zinc BalanceZinc Balance Wolman et al. Wolman et al. Gastroenterology 76: 458Gastroenterology 76: 458--467, 1979467, 1979

-6-4-202468

101214

0 10 20 30

Bal

ance

(mg/

d)

GI losses<=300 g/dGI losses>300 g/d

Zinc in Zinc in EnteralEnteral

NutritionNutrition

Absorption is only 7%Absorption is only 7%Deficiency can occur despite giving 150% Deficiency can occur despite giving 150% of RDA (of RDA (J Am J Am GeriatrGeriatr SocSoc..

1986 May;34(5):3851986 May;34(5):385--8.8.

))Supplements of 220 mg/day have been Supplements of 220 mg/day have been given to correct deficiencies.given to correct deficiencies.

CopperCopper

Absorption: 32% of intake about 0.6Absorption: 32% of intake about 0.6--1.6 1.6 mg/dmg/dExcretion: In bile 0.5Excretion: In bile 0.5--1.5 mg/day1.5 mg/day

Diarrhea increases lossesDiarrhea increases lossesLiver disease reduces losses.Liver disease reduces losses.

CopperCopper

CeruloplasminCeruloplasmin

is an ironis an iron--oxidaseoxidaseOxidizes Ferrous to Ferric form to bind to Oxidizes Ferrous to Ferric form to bind to ApotransferrinApotransferrin for transport.for transport.In tissues Ferric reduced to ferrous by In tissues Ferric reduced to ferrous by riboflavin.riboflavin.

LysyloxidaseLysyloxidase

cross links collagen by:cross links collagen by:Oxidative Oxidative deaminationdeamination of lysine residues to of lysine residues to AllysineAllysine..

Copper deficiency causes Copper deficiency causes neutropenianeutropenia

Copper LevelsCopper Levels

Reduced by deficiency <118 Reduced by deficiency <118 ug/dLug/dLReduced by:Reduced by:

NephroticNephrotic syndromesyndromeGI protein lossGI protein loss

Increased by:Increased by:CancerCancerSepsisSepsisOral ContraceptivesOral Contraceptives

Copper Balance in TPNCopper Balance in TPN ShikeShike

et et al.Gastroenterologyal.Gastroenterology

81:29081:290--7,19817,1981

Protein 1 g/kg/d and 40 kcal/kg/day

Measure:

Plasma Copper Substrates Insulin and Glucagon

Daily 24 hour urine and stool for Cu and N

Day -1 0 3 6 9 12 15 18 21

1.6 mg/day00.8

Copper infused per day: Order Randomized

Copper BalanceCopper Balance

ShikeShike

et al. No Diarrhea 0.3 mg/dayet al. No Diarrhea 0.3 mg/dayDiarrhea 0.5 mg/dayDiarrhea 0.5 mg/dayLiver disease 0.1 mg/dayLiver disease 0.1 mg/day

Jacobson & Western 0.29 mg/dayJacobson & Western 0.29 mg/dayBrit J Brit J NutrNutr 37:10737:107--26, 197726, 1977

PhilippsPhilipps

& & GarnysGarnys

0.5 mg/day0.5 mg/dayAnn Ann IntInt Care 9:221Care 9:221--5, 19815, 1981

ChromiumChromium

Chromium deficiency in animals causes Chromium deficiency in animals causes diabetes.diabetes.In vitro Chromium enhances insulin In vitro Chromium enhances insulin stimulation of glucose oxidation.stimulation of glucose oxidation.Chromium enhances muscle Chromium enhances muscle glycogenesisglycogenesis

ChromiumChromium

Chromium is distributed in all tissues:Chromium is distributed in all tissues:As bound to a peptide As bound to a peptide ChromodulinChromodulinChromodulinChromodulin activates tyrosine activates tyrosine kinasekinase of the of the insulin receptor.insulin receptor.

Cellular levels falls with age.Cellular levels falls with age.Age related glucose intolerance occurs.Age related glucose intolerance occurs.

NUT Clin

Practice 2008;23:325-328

CHROMIUM IN ICUCHROMIUM IN ICU

76 year old woman aortic aneurysm repair76 year old woman aortic aneurysm repairNormal Normal CreatinineCreatinine, LFT and Electrolytes, LFT and ElectrolytesPatients required 58 units insulin/hr to Patients required 58 units insulin/hr to keep BS 8keep BS 8--110 mg/110 mg/dLdLChromic Chloride infused for 24 hoursChromic Chloride infused for 24 hoursInsulin infusion stopped after 12 hoursInsulin infusion stopped after 12 hours

ChromiumChromium

Absorption as an organic complex in food.Absorption as an organic complex in food.Excretion mainly in urine.Excretion mainly in urine.Excretion enhanced by rise in insulin Excretion enhanced by rise in insulin levels.levels.Normal Normal lossedlossed

66--10 10 ug/dug/d

Diabetics (NIDDM) 20 Diabetics (NIDDM) 20 ug/dug/d

ChromiumChromium

Exact requirements not known.Exact requirements not known.In TPN due to glucose infusion In TPN due to glucose infusion requirements may be ~ 20ug/d.requirements may be ~ 20ug/d.

SeleniumSeleniumSelenium resides in cells as Selenium resides in cells as selenocysteineselenocysteine

Selenium is an integral part of:Selenium is an integral part of:Glutathione Glutathione peroxidaseperoxidase ((GSHPxGSHPx))

GSHPxGSHPx

and and SuperoxideSuperoxide

dismutasedismutase::Controls levels of cell peroxide and Controls levels of cell peroxide and andand superoxidesuperoxideControls lipid and membrane Controls lipid and membrane peroxidationperoxidation..

SeleniumSelenium

Selenium is present in all tissues as:Selenium is present in all tissues as:GSHPxGSHPx or or selenocysteineselenocysteine

High concentrations in Liver, Kidney, High concentrations in Liver, Kidney, Pancreas and Heart.Pancreas and Heart.

SeleniumSelenium

Absorbed in duodenum 76Absorbed in duodenum 76--100% of intake100% of intakeCirculates bound to albumin.Circulates bound to albumin.The T1/2 is between 96 and 144 days.The T1/2 is between 96 and 144 days.Excreted in urine (14Excreted in urine (14--20%) and feces (3320%) and feces (33--

58%)58%)Plasma and Plasma and GSHPxGSHPx

levels are sensitive to levels are sensitive to

intake.intake.

SeleniumSelenium

Selenium content of wounds and pus may Selenium content of wounds and pus may be as high as 130 be as high as 130 ugug/L./L.

Fistula fluid 100Fistula fluid 100--380 380 ugug/L/L

SeleniumSelenium

Requirements:Requirements:Human metabolic studies suggest a minimal Human metabolic studies suggest a minimal intake of 20intake of 20--54 54 ug/dug/d

Deficiency causes:Deficiency causes:Muscle painMuscle painCardiomyopathyCardiomyopathy..

Vitamin Requirements in ICU

VITAMIN DOSEEFFECT OF CRITICAL ILLNESS

ICU DOSE

VITAMIN A 3300 IU/d LOW LEVELS UNKNOWN

VITAMIN D 250 IU/d PANCREATITIS NIL

VITAMIN E 10-50 mg/d INCREASED PEROXIDATION 100 mg/d-burns

VITAMIN K 10 mg/week INCREASED PROTIME

WITH ANTIBIOTICS

THIAMINE 3 mg/d LOW LEVELS 5 mg/day

RIBOFLAVINE 3.6 mg/d

NIACIN 40 mg/d

PYRIDOXINE 4 mg/d

VITAMIN C 100 mg/d LOW LEVELS 500 mg/d

ParenteralParenteral Vitamin and Vitamin and AdequacyAdequacy

K N K N JeejeebhoyJeejeebhoy

MBBS, PhD, FRCPCMBBS, PhD, FRCPCSt. MichaelSt. Michael’’s Hospitals HospitalToronto On CanadaToronto On Canada

DisclosuresDisclosures

Consultant:Consultant:NPS IncNPS IncSeaford IncSeaford Inc

Grant:Grant:NPS IncNPS Inc

SummarySummaryMultiMulti--vitamin preparation based on the AMAvitamin preparation based on the AMA--

FDA FDA fromulafromula

has been used for years (JPEN has been used for years (JPEN 1985).1985).This formula has been reformulated by the FDA.This formula has been reformulated by the FDA.The new formulation has increased the levels of The new formulation has increased the levels of Thiamin, Pyridoxine, Ascorbic Acid, Folic acid.Thiamin, Pyridoxine, Ascorbic Acid, Folic acid.Vitamin K has been added to the AMAVitamin K has been added to the AMA--FDA FDA formula.formula.The complex effects of such formulations will be The complex effects of such formulations will be discusseddiscussed

Learning ObjectivesLearning Objectives

Understand the Vitamin requirements for Understand the Vitamin requirements for parenteralparenteral

nutritionnutrition

The effects of illness on requirementsThe effects of illness on requirementsThe difference between the AMAThe difference between the AMA--FDA FDA formula and the new formulaformula and the new formulaThe pro and cons of such a a changeThe pro and cons of such a a changeThe direction for the futureThe direction for the future

Learning Assessment question Learning Assessment question 11

The difference between the old and new The difference between the old and new formulation are:formulation are:

1. Increased Thiamin levels1. Increased Thiamin levels2. Pyridoxine levels2. Pyridoxine levels3. 3. FolateFolate levelslevels4. All of the above4. All of the above

Learning Assessment question Learning Assessment question 22

The DRI for Vitamin A is:The DRI for Vitamin A is:1300 IU1300 IU550 IU550 IU3300 IU3300 IU5000 IU5000 IU

Learning Assessment question Learning Assessment question 33

The UL for Riboflavin is:The UL for Riboflavin is:10 mg10 mg20 mg20 mg100 mg100 mgUnknownUnknown

Learning Assessment AnswersLearning Assessment Answers

1. All of the above1. All of the above2. 33002. 33003. Unknown3. Unknown

Methods to evaluate AdequacyMethods to evaluate Adequacy

Does the formulation reduce risk of Does the formulation reduce risk of deficiency?deficiency?

Stable Stable ““normalnormal”” patientspatientsPatients with Clinical IllnessPatients with Clinical Illness

Maintenance of Normal Blood LevelsMaintenance of Normal Blood LevelsMaintenance of Biochemical FunctionMaintenance of Biochemical Function

Composition of ReformulationComposition of Reformulation

Adequacy of Multivitamin Adequacy of Multivitamin Formulation Formulation

Does it meet the needs of Normal Does it meet the needs of Normal Humans?Humans?

Comparison with DRIComparison with DRILevels in Home Levels in Home ParenteralParenteral Nutrition PatientsNutrition Patients

Does it meet the needs of critically ill Does it meet the needs of critically ill patients?patients?

Risk assessment of DeficiencyRisk assessment of Deficiency•DRIs are reference values that are quantitative estimates of nutrient intakes to be used for planning and assessing diets for healthy people and include:

•Recommended Dietary Allowances (RDAs) as goals for intake.•Estimated Average Requirement (EAR)•Adequate Intake (AI)•Tolerable Upper Level (UL).

Vitamin KVitamin KPhylloquinonesPhylloquinones

are the main dietary source are the main dietary source

of this vitamin.of this vitamin.Small pool size and rapid turnoverSmall pool size and rapid turnoverOnly 10% of liver pool of Vitamin KOnly 10% of liver pool of Vitamin K

MenaquinonesMenaquinones

produced by B. produced by B. Fragilis,EFragilis,E. . coli, coli, EubacteriumEubacterium, , PropinibactirumPropinibactirum

Most in liver with slow turnoverMost in liver with slow turnoverClinically significant deficiency rare with Clinically significant deficiency rare with dietary restrictionsdietary restrictions

Vitamin KVitamin KProteins containing Proteins containing γγ--carboxycarboxy--glutamicglutamic

acid acid

residues (residues (GlaGla) depend upon Vitamin K for ) depend upon Vitamin K for synthesis.synthesis.They are:They are:

Coagulation factorsCoagulation factorsAnticoagulant factors protein C and SAnticoagulant factors protein C and SBone proteins:Bone proteins:

OsteocalcinOsteocalcinMatrix Matrix GlaGla

ProteinProtein

Vitamin KVitamin KIt is unclear if the action of Vitamin K on It is unclear if the action of Vitamin K on bone has a clinically significant role.bone has a clinically significant role.Anticoagulants depress Anticoagulants depress OsteocalcinOsteocalcin

production. No effect on bone in animalsproduction. No effect on bone in animalsMatrix Matrix GlaGla

protein knockout causes protein knockout causes

calcification of arteries.calcification of arteries.MetaMeta--analysis of patients on anticoagulants analysis of patients on anticoagulants show no effect on Bone (show no effect on Bone (OstoporosisOstoporosis

IntInt

1999;9:4411999;9:441--448)448)

Vitamin KVitamin K

020406080

100120140160

Vitamin K ug/day

Vitamin K

RDIRDADRIMVI-12AMA-FDA

Vitamin K: Source in TPNVitamin K: Source in TPNLipid emulsions Lipid emulsions

10% contain 30.8 10% contain 30.8 ugug Phylloquinone/100 Phylloquinone/100 mLmL20% contain 67.5 20% contain 67.5 ugug Phylloquinone/100 Phylloquinone/100 mLmL(JPEN 1993;17:142(JPEN 1993;17:142--44)44)

The The phylloquinonephylloquinone

in lipid is biologically in lipid is biologically available (Am J available (Am J ClinClin

NutrNutr

1998;68:7161998;68:716--21)21)

Patients receiving 25Patients receiving 25--35% of calories as 35% of calories as lipid did not require additional Vitamin K lipid did not require additional Vitamin K over 4 weeks if infusion (JPEN 2004; over 4 weeks if infusion (JPEN 2004; 28:3028:30--3).3).

Vitamin K: Source in TPNVitamin K: Source in TPN

HPN patients (7HPN patients (7--144 months duration)144 months duration)On lipids 1.45 On lipids 1.45 -- ~4.4 g/kg/WEEK~4.4 g/kg/WEEKPhylloquinonePhylloquinone intake from lipid intake from lipid

80.5580.55--~472 ~472 ugug/WEEK (DRI 840 /WEEK (DRI 840 ugug/WEEK)/WEEK)

Vitamin K:TPNVitamin K:TPNThere is no evidence that patients on TPN There is no evidence that patients on TPN need additional Vitamin K if on lipidneed additional Vitamin K if on lipidHPN patients receiving as little 1.46 HPN patients receiving as little 1.46 g/kg/WEEK (~500 g/kg/WEEK (~500 mLmL

20% lipid/WEEK)20% lipid/WEEK)

did not have low levels of vitamin K did not have low levels of vitamin K Hence minimal lipid intake to prevent EFA Hence minimal lipid intake to prevent EFA deficiency will provide enough vitamin Kdeficiency will provide enough vitamin KNew formulation is unnecessary and New formulation is unnecessary and complicates anticoagulation therapy complicates anticoagulation therapy

Vitamin AVitamin A

0100020003000400050006000700080009000

10000

Vitamin A

RDIRDADRIMVI-12AMA-FDA UL

Vitamin AVitamin AAMAAMA--FDA Formula (JPEN 1985;9:179FDA Formula (JPEN 1985;9:179--188)188)

High normal levels of blood retinolHigh normal levels of blood retinolForbes et al. (1997;13:941Forbes et al. (1997;13:941--944)944)

High in 50%High in 50%Low in 1 patientLow in 1 patientClinical deficiency after 30 months of withdrawing Clinical deficiency after 30 months of withdrawing vitamin A in infusionvitamin A in infusion

Mikalunas

et al (J clin

gastroenterol

2001;33:393–396)50% of patients had low levels when infused 3 days/wkDaily infusion restored normal levels

Vitamin A and Acute Vitamin A and Acute PancreatitisPancreatitis

Brit J Brit J SurgSurg

2000;87:3012000;87:301--55

00.20.40.60.8

11.21.41.61.8

2

RETINOL (umol/L)

Admission Trough Discharge

ControlMild PancreatitisSevere Pncreatitis

FDA FDA formulation:Vitaminformulation:Vitamin

A A The formula meets normal DRIThe formula meets normal DRIAdequate for HPN patients if given dailyAdequate for HPN patients if given dailyInadequate if given 3 times a weekInadequate if given 3 times a week

Therefore just adequateTherefore just adequateUpper safe level is 3 times greater than the Upper safe level is 3 times greater than the formulationformulationSevere Severe PancreatitisPancreatitis

patients have low levelspatients have low levels

Critical illness increases oxidative stressCritical illness increases oxidative stressIs the formulation adequate for critically ill Is the formulation adequate for critically ill patients with oxidative stress?patients with oxidative stress?

Vitamin DVitamin D

0200400600800

100012001400160018002000

Vitamin D IU

RDIRDADRIMVI-12FDA-AMAUL

All these recommendations are based not lack of sunlight exposure

Agents causing metabolic bone Agents causing metabolic bone diseasedisease

Toxins: Aluminium, Cadmium, Strontium, Silicon

Drugs: Furosemide, Heparin, Acetate

Deficiency of: Calcium, Phosphorus, MagnesiumVitamin C, Copper, Boron

Excess of:Vitamin

D, Vitamin D, Fluoride

Increase in lumbar spine bone mineral content in patients on long term parenteral

nutrition without

vitamin D supplementation

Verhage

A, Allard JP, Jeejeebhoy

KN

Effect of withdrawing Vitamin DFrom HPN for 4.5+0.2 years

Effect of Vitamin D withdrawal for 4.5 years

Parameter Baseline End1,25(OHD)2 22.8+7.9 61.3+23.1 pmol/L

PTH 0.2+0.1 4.9+1.7 pmol/L

BMC L2-4 0.79+0.06 0.93+0.07 g/cm.sq

AdynamicAdynamic

bone in renal dialysisbone in renal dialysis

AdynamicAdynamic

bone disease (ABD) is increasingly recognized, especially in bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin Ddialysis patients treated with oral calcium carbonate, vitamin D

supplements. (supplements. (Kidney IntKidney Int. 2006 ;70:931. 2006 ;70:931--7).7).

Recently, several reports have suggested that there is a higher Recently, several reports have suggested that there is a higher incidence of low turnover bone in the absence of incidence of low turnover bone in the absence of aluminiumaluminium

exposure in peritoneal dialysis patients than in exposure in peritoneal dialysis patients than in hemodialysishemodialysis

patients. (Adv patients. (Adv PeritPerit

Dial. 1996;12:250Dial. 1996;12:250--6).6).Relative Relative hypoparathyroidismhypoparathyroidism

with mild with mild hypercalcemiahypercalcemia, induced by a , induced by a positive calcium balance, is considered to be one of the major positive calcium balance, is considered to be one of the major causes of this disorder (Adv causes of this disorder (Adv PeritPerit

Dial. 1996;12:250Dial. 1996;12:250--6).6).

AdynamicAdynamic

bone in renal dialysisbone in renal dialysis

9 CAPD patients were treated with low 9 CAPD patients were treated with low calcium and no Vitamin D for 9 months calcium and no Vitamin D for 9 months (Adv (Adv PeritPerit

Dial. 1996;12:250Dial. 1996;12:250--6).6).

ParameterParameter BaselineBaseline PostPost--TreatmentTreatment NormalNormalOsteocalcinOsteocalcin 6.7 6.7 ng/mLng/mL 22.0 22.0 ng/mLng/mL 10+10+iPTHiPTH 21 pg/21 pg/mLmL 129 pg/129 pg/mLmL 50+50+Serum CaSerum Ca +0.25 +0.25 mmolmmol/L/L

Vitamin D in HPNVitamin D in HPN

Patients with osteoporosis should be Patients with osteoporosis should be considered for withdrawal of:considered for withdrawal of:

PTH monitoring if low:PTH monitoring if low:Withdraw Ca and Vitamin D in TPN solutionsWithdraw Ca and Vitamin D in TPN solutions

MVIMVI--12 without Vitamin D should be 12 without Vitamin D should be considered for these patientsconsidered for these patients

OsteoclasitcOsteoclasitc

activity activity markedly increased.markedly increased.OstobalsticOstobalstic

activity like activity like

PagetsPagets

disease:disease:Immature Immature osteoblastsosteoblastsincreasedincreasedMature Mature osteobalstsosteobalstsdecreaseddecreasedPTH normalPTH normalCalcium lowCalcium low

Vitamin EVitamin E

1

10

100

1000

Vitamin E (Log IU)

RDIRDADRIMVI-12FDA-AMAUL

Vitamin E in HPNVitamin E in HPN Average intake 1.5 mg/day (Nutrition 1997; 13:941Average intake 1.5 mg/day (Nutrition 1997; 13:941--44)44)

Vitamin E and HPNVitamin E and HPN Am J Am J ClinClin

NutrNutr

1988;48:13101988;48:1310--55

02468

1012141618

alpha-Tocopherol (umol/L)

ControlHPN

Vitamin E negatively correlated with breath Vitamin E negatively correlated with breath Pentane (P<0.01)Pentane (P<0.01)

P<0.001

CriticaLCriticaL

illness and Antioxidantsillness and Antioxidants Intensive Care Medicine 2005;31:327Intensive Care Medicine 2005;31:327--3737

Antioxidant supplementationAntioxidant supplementation11 articles were analyzed11 articles were analyzedAggregated data:Aggregated data:

Mortality reduced (RR 0.65 CI 0.44Mortality reduced (RR 0.65 CI 0.44--0.97 0.97 P=0.03)P=0.03)Infectious complications not alteredInfectious complications not altered

ThiaminThiamin

0

1

2

3

4

5

6

Thiamin mg/d

RDIRDADRIMVI-12FDA-AMA

ThiaminThiaminThiamin 5 mg/day safe intake in TPN Thiamin 5 mg/day safe intake in TPN

((Am J Am J ClinClin NutrNutr. 1979;32:332. 1979;32:332--8)8)Thiamin levels low normal in HPN patients Thiamin levels low normal in HPN patients (JPEN 1985;9:179(JPEN 1985;9:179--188)188)Thiamin pyrophosphate and Thiamin pyrophosphate and TransketolaseTransketolase

levels normal in HPN patients on Thiamin 3 levels normal in HPN patients on Thiamin 3 g/day (g/day (Am J Am J GastroenterolGastroenterol. 1996;91:2555. 1996;91:2555--99

))

Beriberi and WE described patients not Beriberi and WE described patients not supplemented or orally supplemented.supplemented or orally supplemented.

Vitamin CVitamin C

1

10

100

1000

10000

Vitamin C mg/d

RDIRDADRIMVI-12FDA-AMAUL

Vitamin C: LevelsVitamin C: Levels

AMAAMA--FDA formula: Low levels seen in few patients FDA formula: Low levels seen in few patients (JPEN 1985;9:179(JPEN 1985;9:179--188)188)

Vitamin C and Urine OxalateVitamin C and Urine OxalateAscorbic acid Dehydroascorbic acid

Diketogluconic acid

Threonic acid

Oxalic acid

35-50% of urine oxalate may be from ascorbate metabolismAnn Nutr Metab 1997;41:269-82

Vitamin C and Urine OxalateVitamin C and Urine Oxalate

Vitamin C 500 mg/day

Vitamin C 100 mg/day

595 patients randomized to:595 patients randomized to:Standard careStandard careStandard care+3000 IU E and 3000 mg C/dayStandard care+3000 IU E and 3000 mg C/day

Plasma Vitamin C in Critical illnessPlasma Vitamin C in Critical illness J J SurgSurg ResRes. 2003 ;109:144. 2003 ;109:144--88. .

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Plasma levels

Plasma Vitamin C

mg/dL

0300 mg/day1000 mg/day3000 mg/day

PyridoxinePyridoxine

1

10

100

Vitamin C mg/d

RDIRDADRIMVI-12FDA-AMAUL

PyridoxinePyridoxine

1

10

100

1000

Vitamin C mg/d

Riboflavin Niacin Folate

RDIRDADRIMVI-12FDA-AMAUL

Vitamin BVitamin B

Deficiency of Riboflavin, Pyridoxine, Deficiency of Riboflavin, Pyridoxine, Niacin, Biotin, Niacin, Biotin, FolateFolate

and B12 does not and B12 does not

occur with FDAoccur with FDA--AMA formula when added AMA formula when added daily (JPEN 1985;9:179daily (JPEN 1985;9:179--88)88)MVIMVI--12 given three times a week resulted 12 given three times a week resulted in low levels of Niacin, pyridoxine and in low levels of Niacin, pyridoxine and Riboflavin 1/5 patients on HPN (J Riboflavin 1/5 patients on HPN (J clinclin

GastroenterolGastroenterol

2001;33:3932001;33:393--96) 96)

Vitamin BVitamin B

The daily intake of Riboflavin, Pyridoxine, The daily intake of Riboflavin, Pyridoxine, Niacin and Niacin and FolateFolate

in MVIin MVI--12 is required.12 is required.

The recent increase in the provision of The recent increase in the provision of FolateFolate

is consistent with DRI for women of is consistent with DRI for women of

childbearing age.childbearing age.Increased Pyridoxine has less justification Increased Pyridoxine has less justification but may improve immune response? but may improve immune response?

ConclusionConclusionVitamins are essential and intakes to match DRI Vitamins are essential and intakes to match DRI are justified in stable HPN patients.are justified in stable HPN patients.Higher levels may benefit ICU patients.Higher levels may benefit ICU patients.Inclusion of Vitamin K is of doubtful benefitInclusion of Vitamin K is of doubtful benefitThe complex interactions of Vitamin D, Calcium The complex interactions of Vitamin D, Calcium by the intravenous route and modulation of PTH by the intravenous route and modulation of PTH needs more study.needs more study.Patients with suppressed PTH, Patients with suppressed PTH, adynamicadynamic

bone bone

may benefit from withdrawal of Vitamin D and a may benefit from withdrawal of Vitamin D and a low calcium level in the low calcium level in the infusateinfusate..