Essential Nutrients PDF

Essential (=Indispensable) Nutrient 1) Performs an identifiable biological function 2) “Abnormality” results if omitted from diet, which is corrected when added back to diet 3) Required in the diet because the body cannot make it at all, or cannot make it fast enough to satisfy the need for it Dieta...

Essential (=Indispensable) Nutrient 1) Performs an identifiable biological function 2) “Abnormality” results if omitted from diet, which is corrected when added back to diet 3) Required in the diet because the body cannot make it at all, or cannot make it fast enough to satisfy the need for it Dietary essentiality is different than Metabolic Essentiality Historically… A nutritionally indispensable AA cannot be synthesized by the animal organism out of materials ordinarily available to the cells at a speed commensurate with the demands for normal growth. Borman et al 1946 Metabolic vs Nutritional Definition ... out of materials ordinarily available … In a strictly metabolic sense (i.e., with appropriate precursors available), only LYS, THR and TRP cannot be synthesized other aa: can provide a precursors Leucine can be produced by it’s keto acid as long as there is an amino group that can have an amino group transfer to it from another molecule Keto acid AA transamination Arginine can be synthesized if there is extra citrulline (urea cycle, rare in the diet) in the body Amino group bc it was expensive The chicken that laid the golden egg… 13CO 2 algae fed to the chicken for a month 13C-chicken 13C-algal Eggs fed to human tests 13C-test subjects protein No C12 in the algae Chicken egg with C13 Berthold, H K et al. “Uniformly 13C-labeled algal protein used to determine amino acid essentiality in vivo.” Proceedings of the National Academy of Sciences of the United States of America vol. 88,18 (1991): 8091-5. doi:10.1073/pnas.88.18.8091 PHE – An indispensable AA Chicken synthesized the protein from the algal protein The Egg protein synthesis and turnover in liver was higher than in muscle The Chicken at Day 28 deepest part M: all of them are C12 day 0 all of them are C13 Increase in the proportion of egg protein that contains phelylalanine from the algal protein No phenylalanine with some that are labeled and some not —> no endogenous synthesis of phenylalanine M + 9: phelylalanine from the algae Berthold et al 1991 GLX (GLU + GLN) – A dispensable AA Lower proportion of glutamate: regular one glutamate is extensively metabolized and not phenylalanine 5C hardly any glutamate from the algal protein —> all got metabolized Berthold et al 1991 AA requirement The minimal intake level which represents a single point on a dose-response curve, and that is sufficient to maintain a specific criterion of nutritional adequacy look at oxidation • • • • • • • Phenylalanine growth increases when it’s low Growth and at some point, no increase in growth Reponse breakdown which will increase Plasma AA response protein aa concentration as growth but at some point, a little Nitrogen balance same decrease Direct AA oxidation Indicator AA oxidation 24h AA balance or measure of organ or system function Dose human nutrition should go in the direction of system function bc not a simple model Wolfe RR, Kim IY, Park S, Ferrando A. Tracing metabolic flux to assess optimal dietary protein and amino acid consumption. Exp Mol Med. 2022 Sep;54(9):1323-1331. doi: 10.1038/s12276-022-00817-w. Epub 2022 Sep 8. PMID: 36075948; PMCID: PMC9534933. Experimental approaches General Aspects • All methods should give the same answer but it doesn’t • Subjects should be studied at ≥6 test AA intake levels above and below reqt • Endpoint should show a clear response to change in test AA intake • Question of adaptation to test AA intake • N: 7-10 days for urea pool • CO2: hours to a couple of days Intake 1-13C-AA by IV TEST AA AA Oxidation Label cleaves off before being catabolized and is exhaled in breath (phenylalanine and leucine) Labeled CO2:normal —> tells us if oxidation is higher or lower Special Products nibbling: constant feeding state so flow is constant and pool is homogeneous Synthesis Free AA Pool Feces Urinary Nitrogen into protein to be catabolized Breakdown 13CO 2, H2O Body Protein If we are measuring phenylalaline oxidation: When intake is low=limited aa=limit protein synthesis, so oxidation will be really low and when requirement is reached and there is some excess phenylalanine: oxidation will increase Metabolic response to intake of an essential AA: Direct oxidation Limiting Reqt Excess Elango, Rajavel et al. “Recent advances in determining protein and amino acid requirements in humans.” The British journal of nutrition vol. 108 Suppl 2 (2012): S22-30. doi:10.1017/S0007114512002504 Direct oxidation Clinical/Metabolic • Restricted choice of test AAs (branched chain AA, LYS, PHE). Carboxyl C released when irreversibly committed to oxidation metabolically: when the test aa goes up, the of the free pool goes up —> changing • Free pool changes with changing test AA intake size the volume • Non-negligible tracer – can’t study very low intakes Analytical • Breath collection • Isotope ratio MS (IRMS) for CO2 enrichment, calorimeter for CO2 production • Blood samples • GCMS for AA enrichment Modelling not how we eat but makes the math • Steady state “nibbling” = 24-h / meal feeding that’s possible • Breakpoint increase in oxidation with increasing intake Indicator AA oxidation (IAAO) Test aa isolated from the tracer aa —> gives more flexibility, not limited to the aa producing CO2 • Concept: when a indispensable AA is limiting, then all other indispensable AA will be oxidized (remember that AAs cannot be stored) Lysine Best indicator: phenylalanine Measuring phenylalanine depending on lysine intake • Increasing intake of limiting amino acid will decrease IAAO Oxidation of phenylalanine nutrient requirement Dose of lysine IAAO Elango, Rajavel et al. “Recent advances in determining protein and amino acid requirements in humans.” The British journal of nutrition vol. 108 Suppl 2 (2012): S22-30. doi:10.1017/S0007114512002504 Indicator AA oxidation (IAAO) Boot strap: statistical model to determine breakpoint Clinical/Metabolic • Free choice of test AA, can study zero intake • Tracer AA pool not perturbed with changing test AA intake • PHE, LYS, LEU indicator AAs standard one: phenylalanine Analytical • Breath Collection • IRMS for CO2 enrichment, Calorimeter for CO2 production • Blood samples; Urine samples (non-invasive) • GCMS for AA enrichment Modelling • Steady state “nibbling” = 24-h / meal feeding • Breakpoint decrease in oxidation with increasing intake Integrate concepts of determining AA requirement need to understand what is happening in the graph • Based on what common key principle? • Ethical, compliance, statistical and technological issues • What is the key endpoint for each method? is different for each method • Nitrogen balance • Direct oxidation • Indicator oxidation • Review each and talk through the story to build each graph Summary of all the graphs All of those techniques give the same answer: inflexion point is the requirement Metabolic response to intake of an essential AA: Indicator oxidation Limiting Reqt Elango, Excess Rajavel et al. “Recent advances in determining protein and amino acid requirements in humans.” The British journal of nutrition vol. 108 Suppl 2 (2012): S22-30. doi:10.1017/S0007114512002504 EAR vs. RDA EAR AA intake RDA Estimates of LYS Reqt (mg/kg/d) Meredith et al 1986 Direct Ox’n re-analysed Zello et al 1993 Indicator oxidation Rand and Young 1999 N Balance re-analysed Kriengsinyos et al 2002 Indicator oxidation Kurpad et al 2001 24-h Indicator balance Kurpad et al 2002 24-h Indicator balance 27 37 30 35 29 29 formerly 12 mg/kg/d now EAR = 31 mg/kg/d now -RDA = 38 mg/kg/d (EAR + 2 x cv) 2007: more similar to the DRI Elango, Rajavel et al. “Recent advances in determining protein and amino acid requirements in humans.” The British journal of nutrition vol. 108 Suppl 2 (2012): S22-30. doi:10.1017/S0007114512002504 Re-analysis of N balance data Dose response curve No data 0 nitrogen balance Proposed that it cross the 0 line at 12 mg/kg/d From Jones et al 1956, reanalyzed by Rand and Young 1999 Indispensable AAs in Protein requirement of aa per gram of protein intake 60 mg AA/g protein 50 40 Total IAAs 25% of aa have to be from the 9 essential aa don’t have to have extremely high protein quality • WHO 2002 = 277 mg/g protein vs. • WHO 1985 = 111 mg/g protein 30 20 10 • Adult = Children >1 yo diet of ppl —> we Potentially limiting AAs inconsume low diversity of protein 0 Trp: low requirement, but in real life, can become deficient like lysine with its high requirement So what? • Omnivores with average protein intake – not an issue • Vegans with lower protein intake and lower protein quality – limiting AA is significant issue especially for children bc children have a higher protein requirement per kg than adults do naturally in many cultures, relies • Complementary proteins comes on having diverse protein sources complementary protein: something that • Beans and rice go together • Legumes and grains makes a more complete protein when you mix both • International – food security and diet diversity – very important especially for children Joint FAO/WHO/UNU Expert Consultation on Protein and Amino Acid Requirements in Human Nutrition (2007) https://apps.who.int/iris/handle/10665/43411 AA requirements (EAR mg/kg/d) The science was a really good quality, but we have more advanced statistical methods and curves data, so changes in the requirements FAO/WHO 1985 14 12 10 14 10 7 3 13 FNB/IOM 2003 Phe+Tyr Lys Val Leu Ile Thr Trp Met+Cys His Before thought that histidine was only essential for kids but now know it’s for both 27 doubled 31 19 34 15 16 4 Didn’t double, 13 was the suggested EAR, 15 not it was the DRI (typo) 11 Function: Histidine requirement HIS-free diet for 48 days, followed by repletion • No effect on nitrogen balance suggests that it’s not essential • Decreased protein turnover, PHE oxidation (IAAO) slowing down of protein • • • • • • in HIS (umol/L) concentration plasma did go down Hct Hb (g/L) Ferritin Transferrin (umol/L) Albumin (g/L) PHE oxidation didn’t fit the model Day 0 Day 24 87a 0.49a 165a 76a 36a 47a 45b 0.43b 148b 112b 30b 41b Day 48 34b 0.43b 143b 129ab 30b 41b Accommodation Kriengsinyos, Wantanee et al. “Long-term effects of histidine depletion on whole-body protein metabolism in healthy adults.” The Journal of nutrition vol. 132,11 (2002): 3340-8. doi:10.1093/jn/132.11.3340 Anemia: problem could be low histidine, not necessarily low iron Function: Histidine requirement This is not a deficiency of iron: iron stores increase despite having anemia which suggests the functional effect of histidine —> adaptation of nutrition deficiency —> accommodation HIS-free diet for 48 days, followed by repletion • No effect on nitrogen balance • Decreased protein turnover, PHE oxidation Focused on RBC metabolism bc Hb is high in histidine and is a key aa to heme-gr to bind iron and oxygen • • • • • • HIS (umol/L) (fraction of blood volume Hct hematocrit occupied by RBC) Hb (g/L) that there is Ferritinsuggests more iron stores Transferrin (umol/L) Albumin (g/L) transport iron from intestine to other cells in the body if somebody is iron deficient: transferrin goes up —> but here, transferrin goes down —> suggests that there is an excess of iron despite that anemia (low Hb) Day 0 87a 0.49a 165a 76a 36a 47a Day 24 45b 0.43b 148b 112b 30b 41b Day 48 34b suggests that volume 0.43b lower of RBC 143b suggests anemia ab 129 30b 41b Accommodation Kriengsinyos et al, J Nutr 2002 DRI Report: Status of knowledge of AA requirements Sex and Age “Separate requirements could not be determined for women versus men, or for older adults and the elderly.” Looked at the influence of sex for lysine requirement LYS Reqt – Sex 70 mg/kg BW mg/kg LBM 60 50 40 a b a 30 20 10 0 Men Follicular Luteal Kriengsinyos, Wantanee et al. “Phase of menstrual cycle affects lysine requirement in healthy women.” American journal of physiology. Endocrinology and metabolism vol. 287,3 (2004): E489-96. doi:10.1152/ajpendo.00262.2003 LYS Reqt - Sex 70 body weight mg/kg BW mg/kg LBM Lean body mass b 60 50 a a 40 30 20 10 0 Men Follicular Luteal Kriengsinyos et al, EB abstract 2003 DRI Report: Status of knowledge of AA requirements more data on premature infants bc they are in the hospital • “Separate requirements could not be determined for women versus men, or for older adults and the elderly.” • Pregnancy: “Essentially, there are no data” • Lactation: “Essentially, there are no data” • Data in children based on factorial analysis • Data in infants based on intake of breast milk (AI not EAR/RDA) DRI Report: Status of knowledge of AA requirements Physical Activity “In view of lack of compelling evidence to the contrary, no additional dietary protein is suggested for healthy adults undertaking resistance of endurance exercise” AA requirements We have in hand: We need studies on: • Methods developed • Age groups • Systematic evaluation in DRI • Females Report • Physiological conditions • • • • • • • Prematurity Healthy infants!!! Intravenous feeding Inborn errors Metabolic stress Liver disease Exercise • Functional criteria of adequacy • Conditionally indispensable AAs and special products