Understanding T He Vitamin Supply Chain And Relative Risk .
Understanding the vitamin supply chainand relative risk of transmission offoreign animal diseasesDr. Jerry Shurson and Dr. Pedro UrriolaDepartment of Animal ScienceUniversity of Minnesota
Executive summary Vitamins are essential nutrients required by swine to optimize health, productivity andwell-beingThe U.S. pork industry is dependent on vitamins manufactured in China because there arelimited, and in some cases, there are no other country of origin options to meet industryvolume demands.Initial studies have provided emerging evidence that the African Swine Fever virus(ASFv) can survive in choline chloride, but not vitamin D3. However, it is unknown ifthis virus can survive in other vitamins.The risk of ASFv or other Foreign Animal Diseases (FAD) being introduced from Chinainto the U.S. through vitamin imports appears to be low, but the impact of introduction ishigh.o Vitamin manufacturing involves many highly technical chemical or fermentationprocesses that utilize commonly accepted quality control certification schemesand sanitary processes to meet human food grade, and often pharmaceuticalstandards in the U.S. and E.U. Vitamins imported for use in animal feeds in theU.S. are manufactured in the same facilities and under the same conditions.o There is no distinction between human (pharmaceutical) grade vitamin productionversus animal feed grade production, unlike some other feed additives and byproducts used in the feed industryo Although gelatin used in manufacturing vitamin A and D3 originates frompigskin, there appears to be sufficient thermal treatments used in extracting,concentrating, and sterilizing gelatin to inactivate pathogens.o Some vitamin suppliers visit and audit corn cob suppliers for choline chlorideproduction to verify that there is a killing step in corn cob carrier production.o Only clean, unused, sealed containers and materials (e.g. pallets) are used forpackaging and transporting vitamins to the U.S., usually under hazardousmaterials shipping standards due to high purity All damaged containers andpackages containing vitamins during transport are destroyed and not used inmanufacturing swine feeds.o Once purified vitamins arrive in the U.S., they are distributed to U.S. vitaminpremix manufacturers for blending with carriers. Only carriers produced in NorthAmerica are used by the U.S. vitamin premix manufacturers to minimize the riskof cross-contamination.o Vitamins are produced and transported to the U.S. at the highest purity possiblefor economic reasons. They are not blended with carriers at the locations ofproduction except for choline chloride. Finely ground corn cobs (60%) are addedto some choline chloride products after manufacturing and before transport, andyour supplier should give you information about the procurement and processingof this material to assess the impact on disease transmission.o The chain of custody from manufacturing to delivery to premix manufacturers isup to 120 days, with an additional up to 90 days holding time until premixes aremanufactured, and up to an additional 180 days until vitamin premixes are addedto complete swine feeds and delivered to commercial farms. This extremely longholding period from the time vitamins are manufactured in China until they are2
consumed by pigs greatly exceeds the required holding time for vitamins of up to39 days for 99.99% ASFv degradation inactivation that has been suggested basedon research to determine half-life of ASFv.o The majority of U.S. vitamin importers and premix manufacturers have processesand quality assurance programs in place to prevent the introduction of ASFv intoU.S. swine herds.o However, there are a few unconventional brokers and traders that may importvitamins from China and market them using limited if any biosecurity and qualityassurance control procedures. Obtaining vitamins and premixes from theseentities increases the risk of ASFv introduction.Pork producers are responsible for selecting reputable suppliers of all feed ingredients byasking appropriate questions to avoid potential suppliers that do not follow standards offeed safety.Cross-contamination of vitamin premixes from imported feed ingredients (especiallyporcine derived) and pet foods could occur in multi-species commercial feed mills ifprerequisite or food safety plans are not designed to prevent cross-contamination.The evaluation of the effectiveness of using various mitigation procedures such asthermal treatment, irradiation, pH adjustments, and feed additives for feed and feedingredients contaminated with ASFv is not complete. Most research has focused on theeffectiveness of additives added during complete feed processing with other types ofviruses which have very different characteristics compared with ASFv. However,vitamins are unique compared to other feed ingredients because they are sensitive to highheat treatment and pH, which can substantially reduce their nutritional value. Therefore,options for treating vitamins and vitamin premixes with these methods is likely not aviable option, and if used, vitamin stability evaluations should be conducted to confirmadequate stability or adjust dietary vitamin concentrations to compensate for potentiallosses.Summary of potential risk factors for ASF virus contamination/transmission in the vitaminsupply chain Purchasing vitamin products from unconventional brokers and traders that do not providenecessary documentation of country of origin, quality assurance, and sanitary transportprocedures.Cross-contamination of vitamin premixes from imported feed ingredients (especiallyporcine derived) and pet foods in multi-species commercial feed mills.Use of gelatin derived from pigskin when manufacturing vitamin A and D3.Use of ground corn cobs as a carrier during the choline chloride manufacturing process.3
Current situationExtensive interconnectedness of global trade and human mobility has dramatically increased therisk of transmitting foreign animal diseases (FAD) from endemic countries compared with thosethat do not have these diseases. Several FAD have been identified as potential threats to the U.S.pork industry, especially African Swine Fever (ASFv; Dee et al., 2018).Feed ingredients contaminated with viruses, which includes some vitamins, have been shown tomaintain active virus that could potentially serve as a means of transmission to pigs. Studies haveevaluated the survival of Porcine Epidemic Diarrhea Virus (PEDV), Porcine Delta Corona Virus(PDCoV), and Transmissible Gastroenteritis Virus (TGEV) in feed ingredients and showed nodifferences in survival of PEDV among complete feed, vitamin-trace mineral premix, and otherfeed ingredients tested (Trudeau et al., 2017). However, PDCoV and TGEV survived longer insoybean meal and corn compared to all other feed ingredients and (Trudeau et al., 2017). In arecent study by Dee et al. (2018), surrogate viruses for Foot and Mouth Disease virus (SenecaVirus A), Swine Vesicular Disease virus (Porcine Sapelovirus), PEDV, and Porcine CircovirusType 2 virus survived in vitamin D using the length of time in trans-Pacific and trans-Atlantictransport models. Although ASFv did not survive in vitamin D, it did survive in choline chloridealong with Seneca Virus A, PEDV, and Porcine Circovirus Type 2. These results have raisedquestions about the risk of ASF virus survival in other types of imported vitamins. However, it isimportant to acknowledge that many feed ingredients and pet food products are imported into theU.S. annually. The risk assessment of transmission of ASFv in these feed ingredients and petfood from China has not been determined, but they may pose a greater risk of ASFv and FADvirus transmission than imported vitamins due to less control of cross-contamination fromprocurement or manufacturing and transit to U.S. destinations (Table1).Table 1. Feed ingredients imported into the United States in 2018 (Source: United StatesInternational Trade Commission; https://dataweb.usitc.gov/)IngredientkgCorn grain794,874,396Pork and pork derived products512,302,065Soybeans507,524,609Animal feeds excluding pet food395,205,327Dog and cat food254,881,394Total vitamin imports for human and animal use128,453,000Vitamins represent a significant proportion of total feed ingredient imports (Table 1), and somevitamins (biotin, folic acid, pyridoxine, thiamin, and B12) are almost exclusively, or onlymanufactured in China (Table 2), which is endemic with ASFv. Therefore, U.S. pork producersand their feed suppliers have questioned the relative risk of importing vitamins from China forintroducing ASFv into North America.4
Table 2. Estimates of the quantity and percentage of total vitamins imported into theUnited States from China in 2018 (Source: United States International Trade Commission;https://dataweb.usitc.gov/)Vitamin imports (human and animal use)kgEstimated % of total vitaminimportsTotal91,534,032Vitamin C36,435,93580Vitamin E and related27,689,71055Niacin (B3)9,891,19250Pantothenic acid (B5)4,781,25370Vitamin A2,257,38835Thiamin (B1)2,137,93490Riboflavin (B2)1,507,01650Pyridoxine (B6)1,367,48390Vitamin B12661,10790Folic acid337,10640Other unmixed vitamins and derivatives4,467,90870However, it is important to recognize that 5.1% of imported soybean meal, 11.7% of importedsoybeans, and 4.5% of brewery/distillery by-products are imported from ASFv-affected countries(USDA, 2019). These feed ingredients may be a risk factor for the transmission of ASFv andother foreign animal viruses, but there are no published data documenting the presence orprevalence of viruses in imported feed ingredients.Most vitamin manufacturers produce human and animal grade vitamins using the same qualityassurance and controls that meet human grade standards. Third party certification programs (e.g.GMA – Grocery Manufacturers Association; GMP - Good Manufacturing Practices; FAMI-QS– Feed Additive and preMixture System) are used in vitamin manufacturing facilities, whichlikely minimizes the risk of contamination of vitamin products with ASFv or other viruses(Figure 1). Therefore, the risk of ASFv introduction from vitamins is considered to be low, but ifcontaminated, vitamins can be a vehicle for virus introduction in the U.S.Figure 1. General description of the vitamin supply chain5
This means that sanitation practices must be in place after manufacturing and during transport tofurther minimize the risk of virus contamination. Once these highly concentrated, purifiedchemical forms of vitamins arrive in the U.S., they are blended with carriers (e.g. rice hulls, corncobs) to manufacture vitamin or vitamin-trace mineral premixes, which are added at lowinclusion rates (1 to 10 lbs/ton) to complete swine feeds. The countries of origin of these carriersare almost exclusively in North America, which pose minimal risk of ASFv contaminationbecause this virus is not present in North America.It is important to recognize that not all vitamin suppliers follow strict quality assurance andsanitary transport procedures. Unconventional, non-certified, or uninspected vitamin brokers andtraders exist in the vitamin supply chain, which may pose a greater risk of ASFv introduction.Therefore, pork producers should be diligent when selecting only vitamin suppliers and choosethose that adhere to the highest quality assurance and sanitary transport procedures. In addition,there is potential risk of cross-contamination in multi-species feed mills if other imported feedingredients from ASFv endemic countries are used in manufacturing complete feeds.Vitamins are essential nutrients in swine dietsIt is well established that vitamins are required nutrients in swine diets to avoid deficiencies andoptimize growth, reproduction, health and well-being of pigs (NRC, 2012; Barroeta et al., 2011).Although many commonly used feed ingredients, such as corn, soybean meal, dried distillersgrains with solubles, and wheat middlings contain vitamins, the concentrations, potency, andbioavailability are considered inadequate to meet the pig’s requirements. Therefore, vitaminrequirements are met in commercial swine diets by properly formulating vitamin and vitamintrace mineral premixes used as supplements in complete feeds. A list of required vitaminssupplemented in swine diets is shown in Table 3.Because vitamin supplementation is essential in swine diets, volumes of vitamins imported mustmatch industry needs, and the majority of vitamins used in swine premixes in the U.S. areimported from China, several questions about the potential risk of ASFv transmission at variousstages of the vitamin supply chain need to be answered:1.2.3.4.5.6.Where are vitamins manufactured?What are the processes used to manufacture vitamins?What are the quality control and biosecurity procedures used to manufacture vitamins?Are the processes and ingredients used to manufacture vitamins safe?Are the packaging materials safe?What is the typical length of time from vitamin manufacturing in China until vitamins areconsumed by pigs on commercial farms in the U.S.?7. What is the risk of cross-contamination of shipments of purified vitamins in the supplychain?8. How are vitamin premixes made?9. Are all vitamin product providers reputable?10. What is the additional risk of ASFv transmission in multi-species feed mills comparedwith single species feed mills?6
11. Can additional biosecurity and sanitary practices and traceability be implemented in thevitamin supply chain to minimize risk of virus transmission?12. Are there effective mitigation treatment strategies that can be used to inactivate ASF if itis present?Table 3. Chemical and commercial synthetic forms of vitamins required by pigsVitamin1AD3EK (menadione)Biotin (B7)CholineFolacin (B9)Niacin (B3)Pantothenic acid (B5)Riboflavin (B2)Thiamin (B1)Pyridoxine (B6)Cyanocobalamin (B12)1Chemical forms1RetinolRetinalRetinoic acidCholecalciferolDL-α-tocopheryl acetateD-α-tocopheryl iotinCholine chlorideFolateFolic acidPteroylglutaminc acidNicotinic acidNicotinamideD-calcium pantothenateDL-calcium pantothenatecalcium chloride xamineCyanocobalaminCommercial forms of straights2Vitamin A beadlet – Cross-linkedVitamin A beadlet – Non S. Cong. noncross-linkedVitamin D3 beadlet (A/D3) Cross-linkedVitamin D3 S. Cong.Vitamin D3 SDVitamin D3 drum driedVitamin E acetate (50%)Vitamin E alcohol, naturalMenadione sodium bisulfate (MSB)MSB coatedMenadione dimethylpyriminol bisulfite(MPB)Menadione sodium bisulfate complex(MSBC)Menadione nicotinamide bisulfite MNBBiotinCholine chlorideFolic acidNiacinNiacinamideCalcium pantothenateRiboflavinThiamine HClThiamine MonoPyridoxineCyanocobalaminInformation from NRC (2012)2Information adapted from BASF, Animal Nutrition, 6th edition (2000) and DSM,Optimum Vitamin Nutrition for Pigs, 12th edition (2016)Where are vitamins manufactured?The majority of global vitamin production at needed volumes occurs in China. Given themagnitude of the ASFv epidemic in China, feed ingredients produced in China, including7
vitamins, have become a target for questioning their contribution to the potential risk oftransmission of FADs including ASFv. Table 4 provides estimates of the total production ofvarious vitamins produced in China. Note that with the exception of vitamin A, E, and niacin, 80to 100% of all other vitamins must be imported from China. For biotin, folic acid and vitaminB12, there are no other sources beyond China to acquire these vitamins. Therefore, there arelimited options for sourcing most vitamins from countries or regions outside of China in themarket today. In fact, compared with a previous survey of vitamin manufacturing companies andlocations in China (Enting et al., 2010), it appears that the contributions of Chinesemanufacturers to total global vitamin production has increased during the last 9 years. SeeAppendix 1 for a listing of the major vitamin manufacturers, vitamin products, andmanufacturing location.Table 4. Current estimates of the percentage of global vitamin production from Chinacompared with other countries and regions (data obtained from vitamin industry sources).VitaminChina, European Union, India,Korea,Uruguay,%%%%%A3565D3801010E5842K (MNB)781012Thiamine (B1)9010Riboflavin (B2)502525Niacin (B3)374320Calcium pantothenate (B5)8020Pyridoxine (B6)9010Biotin (B7)100Folic acid (B9)100B12100Vitamin C85What are the processes used to manufacture vitamins?Vitamins are manufactured using proprietary chemical or fermentation processes that involvetime, temperature, and pH conditions that are likely to inactivate viruses if they are present.Vitamin manufacturing is a highly technical, hygienic process suitable for achievingpharmaceutical grade products meeting current human health and safety standards (seeAppendix 2 for photos of vitamin production facilities in China). In fact, there is no distinctionbetween human (pharmaceutical) grade vitamin production versus animal feed grade production,unlike some other feed additives and by-products used in the feed industry. Purified forms ofvitamins are called “straights”, which is the form imported into the U.S. without blending withpremix carriers, except for choline chloride that is imported blended with corn cobs or othercarriers.For fat-soluble vitamins (A, D3, and E), examples of manufacturing processes are shown inFigures A3.1, A3.2, A3.3, and A3.4 in Appendix 3. Examples of raw materials used in8
manufacturing these vitamins and the origin is shown in Table 5, and the temperature andduration of heating processes for vitamins A, D3, and E are shown in Appendix 4. Themanufacturing process for these vitamins generally involves adding ingredients at various stages,dissolution and emulsification, spray granulation, drying, heating, drying, mixing, and sieving.Therefore, there is some thermal exposure during the production process that may be adequate toinactivate any virus if it is present. However, the necessary time and temperature of exposure toinactivate ASFv in vitamins has not yet been determined.The water-soluble vitamins (B vitamins) are produced using various proprietary fermentationand chemical processes. Examples of processes used to produce riboflavin, calcium pantothenicacid, and choline chloride are shown in Figures A3.5, A3.6, and A3.7, respectively inAppendix 3. Additional descriptions of main ingredients and general production processes forvarious forms of vitamin K and other B vitamins are shown in Table A3.1 of Appendix 3. Thetemperature and duration of heating processes for biotin is shown in Appendix 4.Table 5. Examples of composition and origin of raw materials used to manufacture selectedvitamin products produced by Zhejiang Medicine Co., Ltd. in ChinaVitamin productCompositionManufacturing locationVitamin A 650, feed gradeVitamin A acetateGelatinCorn starchGlucoseEthoxyquin/BHTVitamin A 1000, feed gradeSilicon dioxideVitamin A acetateGelatinCorn starchGlucoseEthoxyquin/BHTVitamin D3 500, feed gradeSilicon dioxideVitamin D3 oil(Cholecalciferol)GelatinCorn starchSugarBHTVitamin E – all-rac-alpha-tocopheryl acetate50% feed gradeSilicon dioxideVitamin E acetateSilicon dioxideShaoxing, Zhejiang ProvinceWenzhou, Zhejiang ProvinceXiangyin, Hunan ProvinceHaiyan, Jiaxing ProvinceHohhot, Inner MongoliaYixing, Jiangshu ProvinceNanjing, Jiangshu ProvinceTaiwanShaoxing, Zhejiang ProvinceWenzhou, Zhejiang ProvinceXiangyin, Hunan ProvinceHaiyan, Jiaxing ProvinceHohhot, Inner MongoliaYixing, Jiangshu ProvinceNanjing, Jiangshu ProvinceTaiwanShaoxing, Zhejiang ProvinceWenzhou, Zhejiang ProvinceXiangyin, Hunan ProvinceHaiyan, Jiaxing ProvinceLiuzhou, Guangxi ProvinceYixing, Jiangshu ProvinceNanjing, Jiangshu ProvinceTaiwanShaoxing, Zhejiang ProvinceWuxi, Jiangshu ProvinceQihe, Shangdong ProvinceAlthough vitamin manufacturing facilities are located in Chinese provinces that are endemic withASFv, the
Understanding t he vitamin supply chain and relative risk of transmission of . your supplier should give you information about the procurement and processing of this material to assess the impact on disease transmission. . introducing ASFv into North America. 5 .
Konsumsi asam folat, vitamin B12 dan vitamin C pada ibu hamil tergolong masih rendah, sehingga konsumsi sumber vitamin perlu ditingkatkan untuk mencegah masalah selama kehamilan, seperti anemia, prematur, dan kematian ibu dan anak. Kata kunci: asam folat, ibu hamil, vitamin B12, vitamin C *Korespondensi: Telp: 628129192259, Surel: hardinsyah2010@gmail.com J. Gizi Pangan, Volume 12, Nomor 1 .
Milk Thistle Red Clover Rhodiola St. John’s Wort Soy Bean Tomato Tribulus Terrestris Willow Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Vitamin C Vitamin D3 Vitamin E MISCELLANEOUS Alpha Lipoic Acid Beta Carotene Caffeine Choline Bitartrate Chond. Sulphate Bovine Chond. Sulphate Porcine Ch
Normal vitamin D 36% 9% 55% Vitamin D deficiency* Severe vitamin D deficiency** Normal vitamin D Camargo CA, Jr., Ingham T, Wickens K, et al. Vitamin D status of newborns in New Zealand. Br J Nutr 2010;104:1051 -7. Grant CC, Wall CR, Crengle S, Scragg R. Vitamin D deficiency in early childhood Public Health Nutr. 2009;12(10):1893-1901
25-OH Vitamin D levels* To determine vitamin D status * Only measure if patient is symptomatic and has risk factors for Vitamin D deficiency. Measurement, status and management (see Appendix 1 for flowchart) Vitamin D level Vitamin D status Health effect Management 30 nmol/L Defi
VITAMIN A This vitamin helps your body maintain healthy eyes and skin. VITAMIN C This vitamin helps the body heal cuts and wounds and maintain healthy gums. VITAMIN E This vitamin helps maintain healthy cells throughout your body. WATER Water makes up more than half of your body weight. Your
important.1 But the form of the vitamin D in it is. Look for supplements that contain: Vitamin D3, which is superior at optimizing and maintaining vitamin D levels long-term2 3 Or, if you prefer a plant-based option: Vitamin D2, which is derived from yeast or mushrooms For best absorption, take vitamin D with a meal, especially one that .
vitamin D stores that are further depleted by the lack of vitamin D in maternal breastmilk. These children are at high risk of childhood rickets. Key aims of Vitamin D supplementation To ensure: 1. Maternal Vitamin D levels are replete to avoid neonatal rickets. 2. Vitamin D deficiency is reversed in a timely manner. 3.
VITAMIN D3 VITAMIN D2 Ergosterol Not produced in humans 1/3 activity D3 7-dehydrocholesterol Produced by skin by UVB Fully active 16 VITAMIN D3 1,25(OH) 2VITAMIN D 3 VITAMIN D3 Biologically inactive Does not bind to VDR Nutritional substance 1,25(OH) 2 D 3 Steroid hormone Acts through Vitamin D Receptor (VDR) 17
