Biofortification with Vitamin D - several studies

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The future is bright: Biofortification of common foods can improve vitamin D status - July 2023

Critical Reviews in Food Science and Nutrition Vol 63, 2023 - Issue 4 https://doi.org/10.1080/10408398.2021.1950609
Holly R. Neill ORCID Icon,Chris I. R. Gill ORCID Icon,Emma J. McDonald,W. Colin McRoberts &L. Kirsty P

Vitamin D deficiency is a global concern, linked to suboptimal musculoskeletal health and immune function, with status inadequacies owing to variations in UV dependent cutaneous synthesis and limited natural dietary sources. Endogenous biofortification, alongside traditional fortification and supplement usage is urgently needed to address this deficit. Evidence reviewed in the current article clearly demonstrates that feed modification and UV radiation, either independently or used in combination, effectively increases vitamin D content of primary produce or ingredients, albeit in the limited range of food vehicles tested to date (beef/pork/chicken/eggs/fish/bread/mushrooms). Fewer human trials have confirmed that consumption of these biofortified foods can increase circulating 25-hydroxyvitamin D [25(OH)D] concentrations (n = 10), which is of particular importance to avoid vitamin D status declining to nadir during wintertime. Meat is an unexplored yet plausible food vehicle for vitamin D biofortification, owing, at least in part, to its ubiquitous consumption pattern. Consumption of PUFA-enriched meat in human trials demonstrates efficacy (n = 4), lighting the way for exploration of vitamin D-biofortified meats to enhance consumer vitamin D status. Response to vitamin D-biofortified foods varies by food matrix, with vitamin D3-enriched animal-based foods observing the greatest effect in maintaining or elevating 25(OH)D concentrations. Generally, the efficacy of biofortification appears to vary dependent upon vitamer selected for animal feed supplementation (vitamin D2 or D3, or 25(OH)D), baseline participant status and the bioaccessibility from the food matrix. Further research in the form of robust human clinical trials are required to explore the contribution of biofortified foods to vitamin D status.
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Biofortification's contribution to mitigating micronutrient deficiencies (behind paywall) Jan 2024

Nat Food. 2024 Jan 2. doi: 10.1038/s43016-023-00905-8
Jie Li 1, Cathie Martin 2, Alisdair Fernie 3

Biofortification was first proposed in the early 1990s as a low-cost, sustainable strategy to enhance the mineral and vitamin contents of staple food crops to address micronutrient malnutrition. Since then, the concept and remit of biofortification has burgeoned beyond staples and solutions for low- and middle-income economies. Here we discuss what biofortification has achieved in its original manifestation and the main factors limiting the ability of biofortified crops to improve micronutrient status. We highlight the case for biofortified crops with key micronutrients, such as provitamin D3/vitamin D3, vitamin B12 and iron, for recognition of new demographics of need. Finally, we examine where and how biofortification can be integrated into the global food system to help overcome hidden hunger, improve nutrition and achieve sustainable agriculture.

80 References

1. Healthy diet. WHO https://www.who.int/news-room/fact-sheets/detail/healthy-diet (2020).
2. Sendai Framework for Disaster Risk Reduction 2015–2030 (Asian Disaster Reduction Center, 2015).
3. Van Der Straeten, D. et al. Multiplying the efficiency and impact of biofortification through metabolic engineering. Nat. Commun. 11, 5203 (2020). - PubMed - PMC - DOI
4. Pingali, P. L. Green revolution: impacts, limits, and the path ahead. Proc. Natl Acad. Sci. USA 109, 12302–12308 (2012). - PubMed - PMC - DOI
5. Bouis, H. E., Hotz, C., McClafferty, B., Meenakshi, J. V. & Pfeiffer, W. H. Biofortification: a new tool to reduce micronutrient malnutrition. Food Nutr. Bull. 32, S31–S40 (2011). - PubMed - DOI
6. Siddique, K. H. M., Li, X. & Gruber, K. Rediscovering Asia’s forgotten crops to fight chronic and hidden hunger. Nat. Plants 7, 116–122 (2021). - PubMed - DOI
7. Qaim, M., Stein, A. J. & Meenakshi, J. Economics of biofortification. Agric. Econ. 37, 119–133 (2007). - DOI
8. Petry, N. et al. The proportion of anemia associated with iron deficiency in low, medium, and high human development index countries: a systematic analysis of national surveys. Nutrients 8, 693 (2016). - PubMed - PMC - DOI
9. Bourassa, M. W., Atkin, R., Gorstein, J. & Osendarp, S. Aligning the epidemiology of malnutrition with food fortification: grasp versus reach. Nutrients 15, 2021 (2023). - PubMed - PMC - DOI
10. Pfeiffer, W. H. & McClafferty, B. HarvestPlus: breeding crops for better nutrition. Crop Sci. 47, S-88–S-105 (2007). - DOI
11. Bhardwaj, A. K. et al. Agronomic biofortification of food crops: an emerging opportunity for global food and nutritional security. Front. Plant Sci. 13, 1055278 (2022). - PubMed - PMC - DOI
12. Kumar, S. et al. Breeding and adoption of biofortified crops and their nutritional impact on human health. Ann. N. Y. Acad. Sci. https://doi.org/10.1111/nyas.14936 (2022). - DOI - PubMed
13. Jiang, L., Strobbe, S., Van Der Straeten, D. & Zhang, C. Regulation of plant vitamin metabolism: backbone of biofortification for the alleviation of hidden hunger. Mol. Plant 14, 40–60 (2021). - PubMed - DOI
14. Strobbe, S. & Van Der Straeten, D. Toward eradication of B-vitamin deficiencies: considerations for crop biofortification. Front. Plant Sci. 9, 443 (2018). - PubMed - PMC - DOI
15. Beyer, P. Golden Rice and ‘Golden’ crops for human nutrition. New Biotechnol. 27, 478–481 (2010). - DOI
16. Harjes, C. E. et al. Natural genetic variation in lycopene epsilon cyclase tapped for maize biofortification. Science 319, 330–333 (2008). - PubMed - PMC - DOI
17. Zheng, X., Giuliano, G. & Al-Babili, S. Carotenoid biofortification in crop plants: citius, altius, fortius. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865, 158664 (2020). - PubMed - DOI
18. Bouis, H. E. & Saltzman, A. Improving nutrition through biofortification: a review of evidence from HarvestPlus, 2003 through 2016. Glob. Food Sec. 12, 49–58 (2017). - PubMed - PMC - DOI
19. Low, J. W., Mwanga, R. M., Andrade, M., Carey, E. & Ball, A.-M. Tackling vitamin A deficiency with biofortified sweetpotato in sub-Saharan Africa. Glob. Food Sec. https://doi.org/10.1016/j.gfs.2017.01.004 (2017).
20. Glahn, R. P., Wiesinger, J. A. & Lung’aho, M. G. Iron concentrations in biofortified beans and nonbiofortified marketplace varieties in East Africa are similar. J. Nutr. 150, 3013–3023 (2020). - PubMed - DOI
21. Zhao, T. et al. Global burden of vitamin A deficiency in 204 countries and territories from 1990–2019. Nutrients 14, 950 (2022). - PubMed - PMC - DOI
22. Lockyer, S., White, A. & Buttriss, J. Biofortified crops for tackling micronutrient deficiencies—what impact are these having in developing countries and could they be of relevance within Europe? Nutr. Bull. 43, 319–357 (2018). - DOI
23. Stevens, G. A. et al. Trends and mortality effects of vitamin A deficiency in children in 138 low-income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. Lancet Glob. Health 3, e528–e536 (2015). - PubMed - DOI
24. Martin, C. & Li, J. Medicine is not health care, food is health care: plant metabolic engineering, diet and human health. New Phytol. 216, 699–719 (2017). - PubMed - DOI
25. Martin, C., Zhang, Y., Tonelli, C. & Petroni, K. Plants, diet, and health. Ann. Rev. Plant Biol. 64, 19–46 (2013). - DOI
26. Titcomb, T. J. & Tanumihardjo, S. A. Global concerns with B vitamin statuses: biofortification, fortification, hidden hunger, interactions, and toxicity. Compr. Rev. Food Sci. Food Saf. 18, 1968–1984 (2019). - PubMed - DOI
27. Pollard, C. M. & Booth, S. Food insecurity and hunger in rich countries—it is time for action against inequality. Int. J. Environ. Res. Public Health 16, 1804 (2019). - PubMed - PMC - DOI
28. Fortenberry, M., Rucker, H. & Gaines, K. Pediatric scurvy: how an old disease is becoming a new problem. J. Pediatric Pharmacol. Ther. 25, 735–741 (2020).
29. Willett, W. et al. Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems. Lancet 393, 447–492 (2019). - PubMed - DOI
30. McCollum, E. V., Simmonds, N., Becker, J. E. & Shipley, P. Studies on experimental rickets: XXI. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J. Biol. Chem. 53, 293–312 (1922). - DOI
31. Holick, M. F. et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210, 203–205 (1980). - PubMed - DOI
32. Jäpelt, R. B. & Jakobsen, J. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Front. Plant Sci. 4, 136 (2013). - PubMed - PMC - DOI
33. van Schoor, N. M. & Lips, P. Worldwide vitamin D status. Best Pract. Res. Clin. Endocrinol. Metab. 25, 671–680 (2011). - PubMed - DOI
34. Li, J. et al. Biofortified tomatoes provide a new route to vitamin D sufficiency. Nat. Plants 8, 611–616 (2022). - PubMed - PMC - DOI
35. Simkin, A. J. Genetic engineering for global food security: photosynthesis and biofortification. Plants 8, 586 (2019). - PubMed - PMC - DOI
36. Kumari, M. et al. Vitamin B12 biofortification of soymilk through optimized fermentation with extracellular B12 producing Lactobacillus isolates of human fecal origin. Curr. Res. Food Sci. 4, 646–654 (2021). - PubMed - PMC - DOI
37. Hurrell, R. & Egli, I. Iron bioavailability and dietary reference values. Am. J. Clin. Nutr. 91, 1461S–1467S (2010). - PubMed - DOI
38. Lockyer, S., White, A., Walton, J. & Buttriss, J. Proceedings of the ‘Working together to consider the role of biofortification in the global food chain’ workshop. Nutr. Bull. 43, 416–427 (2018). - DOI
39. Gupta, R. K., Gangoliya, S. S. & Singh, N. K. Reduction of phytic acid and enhancement of bioavailable micronutrients in food grains. J. Food Sci. Technol. 52, 676–684 (2015). - PubMed - DOI
40. Campion, B. et al. Isolation and characterisation of an lpa (low phytic acid) mutant in common bean (Phaseolus vulgaris L.). Theor. Appl. Genet. 118, 1211–1221 (2009). - PubMed - DOI
41. Campion, B. et al. Genetic reduction of antinutrients in common bean (Phaseolus vulgaris L.) seed, increases nutrients and in vitro iron bioavailability without depressing main agronomic traits. Field Crops Res. 141, 27–37 (2013). - DOI
42. Petry, N., Egli, I., Campion, B., Nielsen, E. & Hurrell, R. Genetic reduction of phytate in common bean (Phaseolus vulgaris L.) seeds increases iron absorption in young women. J. Nutr. 143, 1219–1224 (2013). - PubMed - DOI
43. Wiesinger, J. A., Osorno, J. M., McClean, P. E., Hart, J. J. & Glahn, R. P. Faster cooking times and improved iron bioavailability are associated with the down regulation of procyanidin synthesis in slow-darkening pinto beans (Phaseolus vulgaris L.). J. Funct. Foods 82, 104444 (2021). - DOI
44. Sharma, D. C. & Mathur, R. Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid. Indian J. Physiol. Pharmacol. 39, 403–406 (1995). - PubMed
45. Macknight, R. C. et al. Increasing ascorbate levels in crops to enhance human nutrition and plant abiotic stress tolerance. Curr. Opin. Biotechnol. 44, 153–160 (2017). - PubMed - DOI
46. Zhang, H. et al. Genome editing of upstream open reading frames enables translational control in plants. Nat. Biotechnol. 36, 894–898 (2018). - PubMed - DOI
47. Waltz, E. GABA-enriched tomato is first CRISPR-edited food to enter market. Nat. Biotechnol. 40, 9–11 (2022). - PubMed - DOI
48. Nagamine, A., Takayama, M. & Ezura, H. Genetic improvement of tomato using gene editing technologies. J. Hortic. Sci. Biotechnol. 98, 1–9 (2023). - DOI
49. Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on the production and marketing of plant reproductive material in the Union, amending Regulations (EU) 2016/2031, 2017/625 and 2018/848 of the European Parliament and of the Council, and repealing Council Directives 66/401/EEC, 66/402/EEC, 68/193/EEC, 2002/53/EC, 2002/54/EC, 2002/55/EC, 2002/56/EC, 2002/57/EC, 2008/72/EC and 2008/90/EC (Regulation on plant reproductive material) (European Commission, 2023); https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2023:414:FIN
50. Sashidhar, N., Harloff, H. J., Potgieter, L. & Jung, C. Gene editing of three BnITPK genes in tetraploid oilseed rape leads to significant reduction of phytic acid in seeds. Plant Biotechnol. J. 18, 2241–2250 (2020). - PubMed - PMC - DOI
51. Ibrahim, S. et al. CRISPR/Cas9 mediated disruption of inositol pentakisphosphate 2-kinase 1 (TaIPK1) reduces phytic acid and improves iron and zinc accumulation in wheat grains. J. Adv. Res. 37, 33–41 (2022). - PubMed - DOI
52. Zheng, Z. et al. Editing sterol side chain reductase 2 gene (StSSR2) via CRISPR/Cas9 reduces the total steroidal glycoalkaloids in potato. All Life 14, 401–413 (2021). - DOI
53. Zheng, X., Kuijer, H. N. J. & Al-Babili, S. Carotenoid biofortification of crops in the CRISPR era. Trends Biotechnol. 39, 857–860 (2021). - PubMed - DOI
54. Sun, Y. et al. Generation of high-amylose rice through CRISPR/Cas9-mediated targeted mutagenesis of starch branching enzymes. Fronti. Plant Scie. 8, 298 (2017).
55. Zeng, Z. et al. Functional dissection of HGGT and HPT in barley vitamin E biosynthesis via CRISPR/Cas9-enabled genome editing. Ann. Bot. 126, 929–942 (2020). - PubMed - PMC - DOI
56. Nakayasu, M. et al. Generation of α-solanine-free hairy roots of potato by CRISPR/Cas9 mediated genome editing of the St16DOX gene. Plant Physiol. Biochem. 131, 70–77 (2018). - PubMed - DOI
57. Molla, K. A., Sretenovic, S., Bansal, K. C. & Qi, Y. Precise plant genome editing using base editors and prime editors. Nat. Plants 7, 1166–1187 (2021). - PubMed - DOI
58. Food as medicine: translating the evidence. Nat. Med. 29, 753–754 (2023).
59. Department of Economic and Social Affairs, Population Division World Population Prospects: The 2022 Revision (United Nations, 2022).
60. Lips, P. et al. Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur. J. Endocrinol. 180, P23–P54 (2019). - PubMed - DOI
61. van Schoor, N. & Lips, P. Global overview of vitamin D status. Endocrinol. Metab. Clin. North Am. 46, 845–870 (2017). - PubMed - DOI
62. Siddiqee, M. H., Bhattacharjee, B., Siddiqi, U. R. & MeshbahurRahman, M. High prevalence of vitamin D deficiency among the South Asian adults: a systematic review and meta-analysis. BMC Public Health 21, 1823 (2021). - PubMed - PMC - DOI
63. Brito, A. et al. Less than adequate vitamin D status and intake in Latin America and the Caribbean:a problem of unknown magnitude. Food Nutr. Bull. 34, 52–64 (2013). - PubMed - DOI
64. Hussein, D. A. et al. Pattern of vitamin D deficiency in a Middle Eastern population: a crosssectional study. Int. J. Funct. Nutr. 3, 7 (2022). - DOI
65. Zhumina, A. G. et al. Plasma 25-hydroxyvitamin D levels and VDR gene expression in peripheral blood mononuclear cells of leukemia patients and healthy subjects in central Kazakhstan. Nutrients 12, 1229 (2020). - PubMed - PMC - DOI
66. Mogire, R. M. et al. Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis. Lancet Glob. Health 8, e134–e142 (2020). - PubMed - DOI
67. Bi, X., Tey, S. L., Leong, C., Quek, R. & Henry, C. J. Prevalence of vitamin D deficiency in Singapore: its implications to cardiovascular risk factors. PLoS ONE 11, e0147616 (2016). - PubMed - PMC - DOI
68. Otani, S. et al. Spatial epidemiology of vitamin D status in Mongolia. Environ. Epidemiol. 3, 298 (2019). - DOI
69. Hilger, J. et al. A systematic review of vitamin D status in populations worldwide. Br. J. Nutr. 111, 23–45 (2014). - PubMed - DOI
70. Hernando, V. U., Andry, M. M., María Virginia, P. F. & Valentina, A. Vitamin D nutritional status in the adult population in Colombia—an analytical cross-sectional study. Heliyon 6, e03479 (2020). - PubMed - PMC - DOI
71. Shchubelka, K. Vitamin D status in adults and children in Transcarpathia, Ukraine in 2019. BMC Nutr. 6, 48 (2020). - PubMed - PMC - DOI
72. Angeles-Agdeppa, I., Perlas, L. A. & Capanzana, M. V. Vitamin D status of Filipino adults: evidence from the 8th National Nutrition Survey 2013. Mal. J. Nutr. 24, 395–406 (2018).
73. Vitamin D status of New Zealand Adults: Findings from the 2008/09 New Zealand Adult Nutrition Survey (Ministry of Health, 2012).
74. Daniels, L. UK Food Standard Agency Example Menus for Care Homes Contract Reference NUB 246 (2007).
75. Minimum Expenditure Basket (MEB) Analysis (World Food Programme, 2020).
76. McCance, R. A. & Widdowson, E. M. McCance and Widdowson’s The Composition of Foods 7th summary edn (Royal Society of Chemistry, 2015).
77. Government Dietary Recommendations. Government Recommendations for Energy and Nutrients for Males and Females Aged 1–18 Years and 19+ Years. (Public Health England, 2016).
78. Vitamin and Mineral Nutrition Information System (VMNIS) (WHO, 2023); https://www.who.int/teams/nutrition-and-food-safety/databases/vitamin-an...
79. Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements: Vitamin and Mineral Requirements for Human Nutrition (WHO, 2004).
80. Allen, L., De Benoist, B., Dary, O. & Hurrell, R. World Health Organization Guidelines on Food Fortification with Micronutrients (ed. Allen, A.) (WHO, 2006).

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Biofortified tomatoes provide a new route to vitamin D sufficiency - May 2022

Nature Plants volume 8, pages6 11–616 (2022)
Jie Li, Aurelia Scarano, Nestor Mora Gonzalez, Fabio D’Orso, Yajuan Yue, Krisztian Nemeth, Gerhard Saalbach, Lionel Hill, Carlo de Oliveira Martins, Rolando Moran, Angelo Santino & Cathie Martin

Poor vitamin D status is a global health problem; insufficiency underpins higher risk of cancer, neurocognitive decline and all-cause mortality. Most foods contain little vitamin D and plants are very poor sources. We have engineered the accumulation of provitamin D3 in tomato by genome editing, modifying a duplicated section of phytosterol biosynthesis in Solanaceous plants, to provide a biofortified food with the added possibility of supplement production from waste material.
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Biofortification of meat with vitamin D - Jan 2019

CABI Reviews 2018 https://doi.org/10.1079/PAVSNNR201813045 PDF behind paywall
S. K. Duffy, A. K. Kelly, Gaurav Rajauria, J. V. O'Doherty

Vitamin D deficiency in humans is a major health concern and is very much to the forefront of public health policy, particularly in Europe and northern latitudes where sufficient synthesis of vitamin D through sunlight is limited. Therefore, increased importance of dietary vitamin D intake now applies to these problematic areas. Food sources containing natural vitamin D are limiting and traditional measures such as supplements and exogenous fortification are not effective at a population level as general intakes are low and will only meet the needs of those who consume. Therefore, there is a demand for more effective food-based strategic approaches to increase vitamin D intakes, one of which is biofortification of animal feeds to produce a much wider range of sustainable natural vitamin D-enriched foods. Meat is among the few foods that contain natural occurring vitamin D, which makes it an excellent target food for biofortification. Additionally, meat contains the 25-hydroxyvitamin D (25-OH-D) metabolite, which has been shown to have a quicker absorption and is subsequently more effective at raising serum 25-OH-D in humans in comparison with other vitamin D metabolites. This review will discuss the development of vitamin D bio-fortification of animal diets with different vitamin D sources and their potential to produce vitamin D enriched meat including beef and pork meat. Biofortification of meat could contribute up to 25% of individuals estimated average requirement of vitamin D. Additionally, it will also discuss how vitamin D biofortification of animal diets improves product quality.

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Improving vitamin D content in pork meat by UVB biofortification - May 2023

Meat Science Volume 199, May 2023, https://doi.org/10.1016/j.meatsci.2023.109115
H.R. Neill a, C.I.R. Gill a, E.J. McDonald b, R. McMurray b, W.C. McRoberts c, R. Loy c, A. White c, R. Little d, R. Muns d, E.J. Rosbotham a, U. O'Neill e, S. Smyth f, L.K. Pourshahidi a

Highlights

• Food-based strategies are warranted to address suboptimal vitamin D intakes.
• Daily UVB exposure over 9 weeks doubled vitamin D3 concentrations in pork loin.
• UV pigs which stood more during exposure had higher loin vitamin D3 concentrations.

Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 μg/kg), 25(OH)D3 (2.09 vs. 1.65 μg/kg) and total vitamin D activity (22.88 vs. 14.50 μg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementation.
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All 112 Food Source articles

Note: in some cases the animal naturally has vitamin D (much less if indoors or in pond)

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