Optimizing Plant Nutrition for Human Health

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A Systems Approach to Optimizing Plant Nutrition for Human Health Ross M. Welch Robert W. Holley Center for Agriculture & Health at Cornell University

Why Should Plant Nutritionists Improve the Nutritional Quality of Plant Foods?

Why Does Agriculture Exist? To produce food and fiber and provide livelihoods to farmers and profits to the agricultural l and food industries alone? Why do we need Food? because we need Nutrients! Agriculture is the primary source of energy, protein and all essential minerals and vitamins required for human life! Farmers are nutrient providers! Nutrient security not food security should be our goal! If food systems, based in agriculture, cannot provide all the essential nutrients in adequate quantities to sustain human life during all seasons, diseases ensue, societies suffer and development efforts stagnate.

The Known 43 (51) Essential Nutrients for Sustaining Human Life * Air, Water & Protein Lipids-Fat Macro- Trace Vitamins Energy (amino acids) (fatty acids) Minerals Elements (3) (9) (2) (7) (9) (17) (13) Oxygen Water Carbohydrates Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine Linoleic acid Linolenic acid Na K Ca Mg S P Cl Fe Zn Cu Mn I F Se Mo Co (in B 12 ) Cr Si B Ni V As Li Sn A D E K C (Ascorbic acid) B 1 (Thiamin) B 2 (Riboflavin) B 3 (Niacin) B 5 (Pantothenic acid) B 6 (Pyroxidine) B 7 /H (Biotin) B 9 (Folic acid, folacin) B 12 (Cobalamin) *Numerous other beneficial substances in foods are also known to contribute to good health.

Some Major World Risk Factors Causing Deaths Some WHO Major Risk Factors Causing World Deaths in 2000 Occupational safety Risk Factor Unsafe water, sanitation, hygiene Alcohol Unsafe sex Tobacco Malnutrition 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 Number of Deaths (X1000) (World Health Report, 2002) Malnutrition accounts of 30 million deaths per year (about 1 death per second)

Food Systems, Diet and Disease Global food systems are failing to provide adequate quantities of essential nutrients and other factors needed for good health, productivity and well being for vast numbers of people in many developing nations. Green revolution cropping systems have resulted in reduced foodcrop diversity and decreased availability of many micronutrients. Nutrition transitions (double burden of malnutrition) are causing increased rates of chronic diseases (e.g., obesity, cancer, heart disease, stroke, diabetes, osteoporosis) in many nations. Holistic, sustainable improvements in the entire food system are required to solve the massive problem of malnutrition and increasing chronic disease rates in developed and developing countries. Agricultural systems are a major factor affecting human health

Global Food Systems Problems Agriculture s primary focus has been on production alone, with little concern for nutritional or health-promoting qualities of products Nutritionists tend to emphasize unsustainable medical approaches to solve malnutrition problems supplements food fortificants These strategies do not address the underlying causes of malnutrition - dysfunctional food systems based in agricultural systems that t do not have a goal of promoting human health Simplistic views are the norm looking for silver bullet approaches for solutions Agriculture and human health have never been generally recognized as closely linked disciplines

Micronutrient Malnutrition Causes. More severe illness More infant and maternal deaths Lower cognitive development Stunted growth Lower work productivity And ultimately - Lower GDP (e.g. an estimated >5% annual loss in Pakistan) Higher population growth rates

Global Micronutrient Deficiencies > 3 billion people afflicted (Map from USAID)

Worldwide Prevalence of Anemia in Pregnant Women (WHO, 2008)

Other Micronutrient Deficiency Problems Zn deficiency Se deficiency Scurvy (vitamin C) Beriberi (thiamine/b 1 ) Rickets (both vitamin D & Ca deficiencies) Pernicious Anemia (cobalamine/vitamin B 12 ) Folate Riboflavin

% Changes in Cereal & Pulse Production & in Populations Between 1965 & 1999 250 Cereal Production Pulse Production Population 200 150 250 200 150 on (from 1965-1999) on (from 1965 to 1999) 100 50 0 100 50 0 Developing Nations Developing Nations World Developing Nations % Increase in Producti % Increasee in Populati (FAO data, 1999)

Tbl Table to Farm: AN New Agriculture Paradigm (National Academy of Sciences Workshop - Exploring a vision: Integrating knowledge for food and health, 2003) Rouse, T. I. & Davis, D. P. Exploring a vision: Integrating knowledge for food and health. A workshop summary. Board on Agriculture and Natural Resources, Division on Earth and Life Studies, National Research Council of the National Academies of Sciences. 1-88. 2004. Washington, D.C., The National Academies Press.

WHO Global Strategy on Diet, Physical Activity & Health 57 th th World Health Assembly 2004 Agricultural policy and production have great effects on national diets (i.e., health). Governments can influence agricultural production through many policy measures. As emphasis on health increases and consumption patterns change, Member States need to take healthy nutrition into account in their agricultural policies.

International Obesity Task Force, Global Prevention Alliance (2006) Nutrition criteria should be included in agricultural policy Agricultural policy should undergo health impact assessment Support should be provided for agricultural programs aimed at meeting WHO dietary guidelines

New 2006 Mandate for the Food & Agriculture Organization, UN Extended to encompass entire food chain from farm to plate food chain approaches Assistant Director-General, Louise Fresco We are witnessing a paradigm shift away from tonnes, calories and hectares towards issues of quality quality of life, quality of environment, quality of nutrition Puts improved nutrition & health goals into production agriculture goals

Routs to Better Nutrition (The World Bank) the HarvestPlus program is a promising initiative in which the international agricultural and research centers have begun to develop new breeds of staple foods that are rich in key vitamins and minerals using a new approach to fortification termed biofortification. The World Bank, Directions in Development. Repositioning Nutrition as Central to Development. A strategy for large scale action (2006)

Copenhagen Consensus 2008 Global Challenges Ranked Top Five Challenges

Linking Agriculture to Human Health: The Norway Example Necessary policy reorientation ti was made to increase available micronutrient-rich foods within local food systems Implemented agricultural and food production policies in a national nutrition plan of action Provided economic incentives for producer and consumer in support of healthful diets Resulted in sustained improvement in life expectancy and a reduction in deaths from cardiovascular disease and other chronic diseases From: FAO/WHO. Vitamin and mineral requirements in human nutrition, 2 nd ed. 2004

Some Ways Plant Nutrition Can Be Used to Improve Human Health Increase the availability to roots of essential micronutrient metals in the rhizosphere Use fertilizers in ways that increase micronutrients (essential trace elements and vitamins) in edible portions of food crops Design agronomic systems that maximize nutrient output t of farming systems to improve human health Decrease the available levels of toxic heavy metals in the rhizosphere h and translocation ti to edible plant parts

Soil-Plant Factors Effecting Nutrient Composition of Edible Parts Bioavailable content Diagram from Allaway, 1975

Soil-Plant Factors Effecting the Nutritional Quality of Plant Foods Factors effecting available essential element supplies in soils Soil type (ph, organic matter, parent material, subsoil, etc.) Root-soil interactions - rhizosphere effects Agronomic practices (fertilizers, amendments, organic matter, cropping systems, variety selection, etc.) The available supplies of essential minerals (as influenced by genetic & environmental variables) also affect the accumulation of numerous other nutrients (i.e., vitamins) and other health promoting factors accumulated in edible portions of plant foods

Food Systems Approach to IDD Before I After I Importantly also 30% increase in livestock productivity! Using iodized salt can not achieve this benefit. The root cause of I deficiency is not enough I in the soil! Data from Cao, et al., 1994

Se Map of 48 U.S. States Map developed by Drs. Joe Kubota & William H. Allaway

Decade-long, placebo-controlled, controlled double-blind clinical trial 1312 older Americans, 10 years +200 µg Se/day (Se-yeast) 35 placebo 30 Se 25 cases 20 15 10 5 0 31 17 35 12 19 8 lung colorectal prostate RR=.54, P=.082 RR=.36, P=.025 RR=.34, P=.0004 Slide from Gerald F. Combs, Jr.

Grain-Se Level Using the Selenium Fertilizer Tool to Improve Sl Selenium Status Stt of fth the FiihP Finish People Se Eaten Daily Grain Se (µg kg -1 ) e intake (µg da aȳ 1 ) Daily S 300 200 100 0 150 100 50 0 Selenium added to NPK fertilizers for cereals 1984 (1984-2004) 84 86 88 90 92 94 96 98 00 02 04 Y E A R S 16 mg kg -1 6 mg kg -1 10 mg kg -1 Adding Se to fertilizers greatly > Se in cereal grain Adding Se to fertilizers greatly > Se eaten each day Resulted in a doubling of the blood-se levels in the whole Finish population From: Combs, 2005

Effects of Increasing Se Fertilizer Rates on Wheat-Grain Se Levels (From Lyons et al., 2004)

Link Between Zn-Deficient Soils & Zn Deficiency in Humans Wide Deficiency Medium deficiency Zn-Deficient Soils Zn-Deficient Humans Figure from A. Green, 2009

Effects of Zinc Fertilization on Wheat Yield & Grain Level Zn application Zn concentration Increases in yield by Zn Fertilizer methods Whole shoot Grain Whole shoot Grain (mg kḡ 1 ) (%) Control 10 10-100 Soil 19 18 109 265 Seed 12 10 79 204 Foliar 60 27 40 124 Soil + foliar 69 35 92 250 Seed + foliar 73 29 83 268 Using both soil and foliar Zn fertilizers can maximize grain yields and grain-zinc Yilmaz et al., 1997

Effects of Increasing Zn Fertilizer Rates on Wheat Grain-Zn Levels (From Genc et al., 1999)

N-Zn Relationships in Wheat Grain [Zn] (mg.kg -1 ) Grain 120 100 80 60 40 20 Low Soil Zn Supply No Foliar Application R 2 = 0.1214 01214 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Grain [N] (%) ) Grain [Zn] (mg.kg -1 ) 120 100 80 60 40 20 High Soil Zn Supply No Foliar Application R 2 = 0.7917 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Grain [N] (%) Grain [Zn] (mg.kg -1 ) 120 100 80 60 40 20 0 Low Soil Zn Supply Foliar Zn Application R 2 = 08948 0.8948 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Grain [N] (%) Grain [Z Zn] (mg.kg -1 ) 120 100 80 60 40 20 High Soil Zn Supply Foliar Zn Application R 2 = 0.826 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Grain [N] [](%) Kutman et al., 2009, in press

Effects of Crop Rotations on Wheat Grain-Cu (mg/kg, dry wt.) Wheat-G Grain Cu 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3 Crop Rotation Wheat-Wheat Lupin-Wheat Pea-Wheat Data from King et al., J. Agron. & Crop Sci. 169: 37-48 (1992)

Effects of Maize Intercropping on Fe Deficiency in Peanuts Mono-cropping Intercropping (Zuo et al., Plant and Soil, 2000)

Effect of Intercropping (Maize-Peanut) on Fe Levels in Peanuts ) kg DW) 250 200 150 100 (mg/k150 50 0 Mono Inter Shoot Root Seeds (Zuo et al., Plant and Soil, 2000)

Staple Food Crop Biofortification

HarvestPlus Biofortification Program Strategy Breed for micronutrient-dense staple food crops (using the best traditional breeding practices and modern biotechnology) to achieve provitamin A, iron, and zinc concentrations that can result in measurable improvements in the nutritional status of target populations

HarvestPlus Progress Shown the human efficacy of biofortified Orange-flesh sweet potatoes (also effectiveness shown) High-Fe rice Shown enough genetic diversity in bioavailable levels of Fe and/or Zn in Wheat Beans to have measurable effects in humans

The Importance of Bioavailability Bioavailable amount of a trace element in a meal, not the total amount, is the critical factor for human health Most staple plant foods (cereal grains and legume seeds) fed alone contain very low levels of bioavailable Fe (e.g., about 5%) because of the antinutrients they contain (phytate, polyphenols, etc.) Increasing the bioavailability of Fe from 5% to 30% would have the same effect as increasing total amounts of Fe in staples by 6 fold

Some Ways to Improve Fe and Zn Bioavailability Increase promoter substances Ascorbic acid (vitamin C) Meat factor(s) () Sulfur-containing amino acids (e.g., cysteine) Provitamin A carotinoids (vitamin A) Prebiotics (e.g., inulin) Certain fibers (e.g., sugar beet fiber) Decrease D antinutrients t i t Phytic acid (myo-inositolhexaphosphoric acid) Certain polyphenolics, fibers, etc. Increase / introduce other micronutrient-rich compounds (phytoferritin, hemoglobin, etc.)

The Phytate Conundrum to Decrease or Not to Decrease in Staple Plant Foods Phytate is a known antinutrient that has been shown to inhibit the bioavailability of Fe, Zn, Ca and other polyvalent cations (e.g., Cd, Pb) in humans fed staple plant foods Phytate has also been shown to provide health benefits (e.g., colon cancer prevention) Phytate plays essential roles for all life including higher plants (essential for i-rna editing enzyme; storage site for seed-p, -Fe, -Mg, etc.)

Flavonoid Fe(III)-binding Sites R 1 HO 3' 2' B 8 O 2 1' 7 6' A C 5' 4' OH H 6 5 4 3 R 2 OH O Kaempferol R 1 = H, R 2 = OH Astragalin R 1 =H,R 2 = O-glucoside (kaempferol-3-o-glucoside) Quercetin R 1 = OH, R 2 = H Quercitrin R 1 = OH, R 2 = O-rhamnoside

Structure of Ferritin

Bioavailable Fe in Intrinsically 55 Fe-labeled Soybeans (Tokyo cv.) Fed to Fe-depleted Women Feeding day Soy soup Soy muffin (% absorbed) a (% absorbed) a Day 14 25.9 28.7 Day 28 24.5 27.0 a Mean of 18 subjects with depleted Fe stores Tokyo soybeans contained 30-50% of their total Fe as phytoferritin and 2.1% phytic acid ( 30:1 phytate to Fe molar ratio). Data from Murray-Kolb et al., 2002

The Role of Beneficial Hind Gut Microorganisms on Human Health Beneficial Bacteria

The Human Body & Microbiota: the Superorganism Human body contains 10 trillion (10 13 ) cells Intestine contains 100 trillion (10 15 ) microbes (60% of fecal dry weight) Metabolic activity of these microbes is equal to that of the vital organs in the body Microbes perform a host of functions both mutualistic and symbiotic.

Intestinal Microflora Interactions Some beneficial roles of healthful gut bacteria Non-digestible carbohydrates SCFA gene induction, > Mineral absorption Bound phytonutrients available phytonutrients, > Health Lignans Phytoestrogens < Cancers Antioxidants Available antioxidants Epithelial protection, > Gut health Sphingolipids Sphingosine > Cell growth

Prebiotic Oligosaccharides Lactulose Fructo-oligosaccharides (inulin, levan, etc.) Galacto-oligosaccharides Soybean oligosaccharides Lactosucrose Isomalto-oligosaccharidesoligosaccharides Gluco-oligosaccharides Xylo-oligosaccharidesoligosaccharides Palatinose (isomaltulose) Resistant starch

β(2-1) 1)-linked Inulin Type Fructans (Prebiotics) β(2-1)-bond 1-ketose From: S. van Zanten s Honors Thesis, 2008

Some Inulin Effects on Mineral Bioavailability Stimulates bifidobacteria and lactobacilli growth in the hind gut increases colon acetate, propionate and butyrate levels through fermentation lowers the ph within the lumen of the colon stimulates proliferation of epithelial intestinal cells in the colon induces increased mineral absorption in the colon Increases metal solubility and paracellular uptake from large intestine Induces Calbindin-D9k gene expression in plasma membrane of mucosa cells in the colon Induces mrnas expression that code for Fe transport proteins by mucosal cells in both the colon and duodenum Increases deposition of Ca into bones in post-menopausal women Stimulates true Ca absorption in adolescents Increases Fe bioavailability from maize-soy diets in pigs Stimulates apparent absorption of Fe, Zn, and Cu in monogastric animals Stimulates phytate degradation in the gut Increases Cu absorption in post-menopausal women

Effects of Dietary Inulin on Iron Bioavailability in Pigs (i.e e., Bioav vailable Fe) etion ) n Repl ncy (% Hem moglobi Efficie 35 33 31 29 27 25 23 21 19 17 15 a a b 5 week study n = 7-8 0% Inulin 2% Inulin 4% Inulin Maize-soybean-based diet containing 0.8 % phytate Yasuda et al. J. Nutr. 136:3033-3038 (2006)

Effects of 4% Dietary Inulin on Bacterial Populations in the Pig Cecum Inulin + Inulin Tako et al., British J. Nutr. (2007)

Pig Duodenal Mucosal Cell mrna Expression i (+/- Inulin Diets) t ) Con (0% Inulin) Trt (4% Inulin) 15 12 a 9 AU b 6 a a a a 3 b a b b b a a a b 0 Ferritin DMT1 TfR Dcytb HFE Mucin Ferroportin Tako et al., British J. Nutr. (2007)

Increasing Available Fe Supplies What Needs to be Done? Increase crop productivity Making more land available for diversifying food crops Increase Fe density in edible parts Supply more available Fe to the plant (soil fertilizers/foliar spays?) Increase Fe uptake efficiency Increase Fe translocation rates (xylem & phloem) Increase Fe accumulation in edible parts (e.g., seed & grain) Avoid Fe toxicity in the plant Increase bioavailable Fe level in edible plant parts Accumulate Fe in bioavailable forms Increase promoters (i.e., enhancer substances) Decrease inhibitors (i.e., antinutrients); use caution Increase Zn, provitamin A carotenoids, etc. Using: conventional breeding (short term) transgenic approaches (longer term) Use in combination with complementary foods containing promoter substances (livestock & fish meats, foods high in ascorbic acid, etc.) Re-diversify farming systems to assure sustainability

Agriculture s Agenda For Better Health Item 1: Declare a goal of agriculture to produce high h quality food that promotes human health and well-being in sustainable ab ways. Item 2: Design seeds, cropping & livestock systems that help achieve primary goal design for maximum nutrient output of farming systems. Item 3: Genetically modify food crops, increasing nutritional and health while promoting crop productivity. Item 4: Use agronomic practices (e.g., cropping systems and fertilizers) to improve nutrient output of farming systems. Item 5: Define sustainable agriculture, as agriculture that yields healthy foods for healthy and productive people!

Sir Albert Howard related subjects as agriculture, food, nutrition and health have become split up into innumerable rigid and self-contained little units, each in the hands of some group of specialists. The experts, as their studies become concentrated on smaller and smaller fragments, soon find themselves wasting their lives in learning more and more about less and less. The result is the confusion and chaos now such a feature of the work of experiment stations and teaching centers devoted to agriculture and gardening. Everywhere knowledge increases at the expense of understanding. The remedy is to look at the whole field covered by crop production, animal husbandry, food, nutrition, and health as one related subject, and then to realize the great principle that the birthright of every crop, every animal, and every human being is health. March, 1945 In: Rodale, J.I. 1945. Pay Dirt, Farming & Gardening with Composts. Rodale Books, Inc., Emmaus, Penn. p. vii. Western civilisation is suffering from a subtle form of famine a famine of quality. November, 1947