A comparison of the effect of omega-3 alone versus omega-3/Vitamin D3 co-supplementation therapy on 25-hydroxyvitamin D levels in adults with vitamin D deficiency
Main Article Content
Keywords
vitamin d3, omega-3, vitamin d toxicity, cardiovascular disease, covid-19
Abstract
Background: Omega-3 fatty acid (n-3FA) supplementation may improve total hydroxyvitamin D (25OHD) levels in people with normal or low vitamin D levels. However, there was no agreement on the potential therapeutic benefit of n-3FA on vitamin D toxicity. Objective: The current randomized controlled clinical study (RCT) sought to determine if daily omega-3 fatty acid (n-3FA) supplementation affected 25-hydroxyvitamin D (25OHD) levels. Methods: One hundred and twenty Jordanians aged 22 to 55 were randomly allocated into three groups supplemented with the dose of 50,000 IU VD3 taken weekly (D3) alone, 300 mg n-3FA taken daily (n-3FA) alone, or their combination (50,000 IU VD3 taken weekly + 300 mg n-3FA taken daily (D+). In addition, fasting baseline and follow-up (ten weeks; eight weeks supplementation plus two weeks washout) of serum 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), calcium, and leptin were assayed. Results: The n-3FA supplementation significantly decreased mean serum 25OHD levels (11.97±4.6 vs 16.5±4.8, P<0.001) compared with their peers in the D3 group who showed a significant increase in 25OHD levels (41.15±11.7 vs 19.34±6.8, P<0.001). The follow-up PTH mean levels were proportionally accompanied by significant alterations of 25OHD levels in the two study groups. Conclusions: This novel RCT provides that eight weeks of n-3FA therapy significantly reduced 25OHD levels, which adverse effects may accompany vitamin D status and its health-related consequences, such as bone homeostasis, cardiovascular disease, and COVID-19 conditions.
References
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14. Binkley N, Gemar D, Engelke J, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011;96(4):981-8. https://doi.org/10.1210/jc.2010-0015
15. Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behaviour in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909. https://doi.org/10.1371/journal.pone.0043909
16. Barham A, Mohammad B, Hasoun L, et al. The combination of omega-3 fatty acids with high doses of vitamin D3 elevate A1c levels: A randomized Clinical Trial in people with vitamin D deficiency. Int J Clin Pract. 2021;75(11):e14779. https://doi.org/10.1111/ijcp.14779
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18. Malesa-Ciećwierz M, Usydus Z. Vitamin D: can fish food-based solutions be used for reduction of vitamin D deficiency in Poland? Nutrition. 2015;31(1):187-92. https://doi.org/10.1016/j.nut.2014.07.003
19. Jakobsen J, Smith C, Bysted A, Cashman KD. Vitamin D in Wild and Farmed Atlantic Salmon (Salmo Salar)-What Do We Know? Nutrients. 2019;11(5):982. https://doi.org/10.3390/nu11050982
20. Korkor AB, Bretzmann C. Effect of fish oil on vitamin D absorption. Am J Kidney Dis. 2009;53(2):356. https://doi.org/10.1053/j. ajkd.2008.11.010
21. Rapuri PB, Kinyamu HK, Gallagher JC, Haynatzka V. Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women. J Clin Endocrinol Metab. 2002;87(5):2024-32. https://doi.org/10.1210/jcem.87.5.8475
22. Björkman M, Sorva A, Tilvis R. Responses of parathyroid hormone to vitamin D supplementation: a systematic review of clinical trials. Arch Gerontol Geriatr. 2009;48(2):160-6. https://doi.org/10.1016/j.archger.2007.12.005
23. Smith LM, Gallagher JC. Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials. J Intern Med. 2019;286(6):651-9. https://doi.org/10.1111/joim.12950
24. Yakout SM, Al-Daghri NM, Bukhari I, et al. Vitamin D level and its relation to muscle and fat mass in adult male Arabs. Saudi J Biol Sci. 2020;27(9):2452-6. https://doi.org/10.1016/j.sjbs.2020.07.002
25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. Sep 2000;72(3):690-3. https://doi.org/10.1093/ajcn/72.3.690
26. Kim JH, Park H, Lee J, et al. Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age. J Epidemiol Community Health. 2016;70(5):466-72. https://doi.org/10.1136/jech-2015-206315
27. Manson JE, Cook NR, Lee IM, et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23-32. https://doi.org/10.1056/NEJMoa1811403
28. Abellán R, Mansego ML, Martínez-Hervás S, et al. Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations. Atherosclerosis. 2011;219(2):900-6. https://doi.org/10.1016/j.atherosclerosis.2011.09.018
29. Lupton JR, Faridi KF, Martin SS, et al. Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. J Clin Lipidol. 2016;10(1):72-81.e1. https://doi.org/10.1016/j.jacl.2015.09.006
30. Aydin E, Altin C, Özcan Söylev G, Tekindal MA, Ağildere M. Assessment of Subclinical Atherosclerosis in Vitamin D Deficiency. Ultrasound Q. 2019;35(2):142-146. https://doi.org/10.1097/ruq.0000000000000386
31. Playford MP, Dey AK, Zierold C, et al. Serum active 1,25(OH)(2)D, but not inactive 25(OH)D vitamin D levels are associated with cardiometabolic and cardiovascular disease risk in psoriasis. Atherosclerosis. 2019;289:44-50. https://doi.org/10.1016/j.atherosclerosis.2019.08.006
32. Hafez M, Musa N, Abdel Atty S, Ibrahem M, Abdel Wahab N. Effect of Vitamin D Supplementation on Lipid Profile in Vitamin D-Deficient Children with Type 1 Diabetes and Dyslipidemia. Horm Res Paediatr. 2019;91(5):311-318. https://doi.org/10.1159/000500829
33. Dastorani M, Aghadavod E, Mirhosseini N, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reprod Biol Endocrinol. 2018;16(1):94. https://doi.org/10.1186/s12958-018-0413-3
34. Mehdawi A, Mohammad BA, Mosleh I, et al. The combined effect of omega-3 fatty acid and vitamin D3 on oxidized LDL-C and non-HDL-C levels in people with vitamin D deficiency: A randomized controlled trial. J Cardiovasc Pharmacol. 2023; ;81(4):251-8. https://doi.org/10.1097/fjc.0000000000001398
35. Habash M, Al-Shakhshir S, Abusamak M, Mohammad MY, AbuSamak M. The association of coffee consumption rate with serum 25-hydroxyvitamin D, non-HDL levels, and TC/HDL ratio in females with vitamin D deficiency. Womens Health (Lond). Jan-Dec 2022;18:17455057221112268. https://doi.org/10.1177/17455057221112268
2. Al-Shaer AH, Abu-Samak MS, Hasoun LZ, Mohammad BA, Basheti IA. Assessing the effect of omega-3 fatty acid combined with vitamin D3 versus vitamin D3 alone on estradiol levels: a randomized, placebo-controlled trial in females with vitamin D deficiency. Clin Pharmacol. 2019;11:25-37. https://doi.org/10.2147/cpaa.s182927
3. Abu-Samak MS, Hasoun LZ, Barham A, et al. The supplementary effects of omega-3 fatty acid alone and in a combination with vitamin D3 on serum leptin levels: A randomized clinical trial on men and women with vitamin D deficiency. Pharmacia. 2021;68(3):517-25.
4. Bader DA, Abed A, Mohammad BA, et al. The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency. Nutrients. 2023;15(5):1188.
5. Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. Jama. 2019;322(8):736-45. https://doi.org/10.1001/ jama.2019.11889
6. Dudenkov DV, Yawn BP, Oberhelman SS, et al. Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year Population-Based Study. Mayo Clin Proc. 2015;90(5):577-86. https://doi.org/10.1016/j.mayocp.2015.02.012
7. Hassler A, Lamy O, Rossier A, Sartori C, Gachoud D. Severe hypercalcemia after a single high dose of vitamin D in a patient with sarcoidosis. Rheumatol Int. 2013;33(11):2955-6. https://doi.org/10.1007/s00296-012-2523-0
8. Jain AP, Aggarwal KK, Zhang PY. Omega-3 fatty acids and cardiovascular disease. Eur Rev Med Pharmacol Sci. 2015;19(3):441-5.
9. Brennan Laing B, Cavadino A, Ellett S, Ferguson LR. Effects of an Omega-3 and Vitamin D Supplement on Fatty Acids and Vitamin D Serum Levels in Double-Blinded, Randomized, Controlled Trials in Healthy and Crohn’s Disease Populations. Nutrients. 2020;12(4):1139. https://doi.org/10.3390/nu12041139
10. Lee SM, Son YK, Kim SE, An WS. The effects of omega-3 fatty acid on vitamin D activation in hemodialysis patients: a pilot study. Mar Drugs. 2015;13(2):741-55. https://doi.org/10.3390/md13020741
11. Jordan RE, Adab P, Cheng KK. Covid-19: risk factors for severe disease and death. Bmj. 2020;368:m1198. https://doi.org/10.1136/bmj.m1198
12. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr. 2020;74(11):1498-1513. https://doi.org/10.1038/s41430-020-0558-y
13. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30. https://doi.org/10.1210/jc.2011-0385
14. Binkley N, Gemar D, Engelke J, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011;96(4):981-8. https://doi.org/10.1210/jc.2010-0015
15. Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P. Docosahexaenoic acid for reading, cognition and behaviour in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909. https://doi.org/10.1371/journal.pone.0043909
16. Barham A, Mohammad B, Hasoun L, et al. The combination of omega-3 fatty acids with high doses of vitamin D3 elevate A1c levels: A randomized Clinical Trial in people with vitamin D deficiency. Int J Clin Pract. 2021;75(11):e14779. https://doi.org/10.1111/ijcp.14779
17. Alhabeeb H, Kord-Varkaneh H, Tan SC, et al. The influence of omega-3 supplementation on vitamin D levels in humans: a systematic review and dose-response meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2022;62(11):3116-23. https://doi.org/10.1080/10408398.2020.1863905
18. Malesa-Ciećwierz M, Usydus Z. Vitamin D: can fish food-based solutions be used for reduction of vitamin D deficiency in Poland? Nutrition. 2015;31(1):187-92. https://doi.org/10.1016/j.nut.2014.07.003
19. Jakobsen J, Smith C, Bysted A, Cashman KD. Vitamin D in Wild and Farmed Atlantic Salmon (Salmo Salar)-What Do We Know? Nutrients. 2019;11(5):982. https://doi.org/10.3390/nu11050982
20. Korkor AB, Bretzmann C. Effect of fish oil on vitamin D absorption. Am J Kidney Dis. 2009;53(2):356. https://doi.org/10.1053/j. ajkd.2008.11.010
21. Rapuri PB, Kinyamu HK, Gallagher JC, Haynatzka V. Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women. J Clin Endocrinol Metab. 2002;87(5):2024-32. https://doi.org/10.1210/jcem.87.5.8475
22. Björkman M, Sorva A, Tilvis R. Responses of parathyroid hormone to vitamin D supplementation: a systematic review of clinical trials. Arch Gerontol Geriatr. 2009;48(2):160-6. https://doi.org/10.1016/j.archger.2007.12.005
23. Smith LM, Gallagher JC. Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials. J Intern Med. 2019;286(6):651-9. https://doi.org/10.1111/joim.12950
24. Yakout SM, Al-Daghri NM, Bukhari I, et al. Vitamin D level and its relation to muscle and fat mass in adult male Arabs. Saudi J Biol Sci. 2020;27(9):2452-6. https://doi.org/10.1016/j.sjbs.2020.07.002
25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. Sep 2000;72(3):690-3. https://doi.org/10.1093/ajcn/72.3.690
26. Kim JH, Park H, Lee J, et al. Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age. J Epidemiol Community Health. 2016;70(5):466-72. https://doi.org/10.1136/jech-2015-206315
27. Manson JE, Cook NR, Lee IM, et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23-32. https://doi.org/10.1056/NEJMoa1811403
28. Abellán R, Mansego ML, Martínez-Hervás S, et al. Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations. Atherosclerosis. 2011;219(2):900-6. https://doi.org/10.1016/j.atherosclerosis.2011.09.018
29. Lupton JR, Faridi KF, Martin SS, et al. Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. J Clin Lipidol. 2016;10(1):72-81.e1. https://doi.org/10.1016/j.jacl.2015.09.006
30. Aydin E, Altin C, Özcan Söylev G, Tekindal MA, Ağildere M. Assessment of Subclinical Atherosclerosis in Vitamin D Deficiency. Ultrasound Q. 2019;35(2):142-146. https://doi.org/10.1097/ruq.0000000000000386
31. Playford MP, Dey AK, Zierold C, et al. Serum active 1,25(OH)(2)D, but not inactive 25(OH)D vitamin D levels are associated with cardiometabolic and cardiovascular disease risk in psoriasis. Atherosclerosis. 2019;289:44-50. https://doi.org/10.1016/j.atherosclerosis.2019.08.006
32. Hafez M, Musa N, Abdel Atty S, Ibrahem M, Abdel Wahab N. Effect of Vitamin D Supplementation on Lipid Profile in Vitamin D-Deficient Children with Type 1 Diabetes and Dyslipidemia. Horm Res Paediatr. 2019;91(5):311-318. https://doi.org/10.1159/000500829
33. Dastorani M, Aghadavod E, Mirhosseini N, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reprod Biol Endocrinol. 2018;16(1):94. https://doi.org/10.1186/s12958-018-0413-3
34. Mehdawi A, Mohammad BA, Mosleh I, et al. The combined effect of omega-3 fatty acid and vitamin D3 on oxidized LDL-C and non-HDL-C levels in people with vitamin D deficiency: A randomized controlled trial. J Cardiovasc Pharmacol. 2023; ;81(4):251-8. https://doi.org/10.1097/fjc.0000000000001398
35. Habash M, Al-Shakhshir S, Abusamak M, Mohammad MY, AbuSamak M. The association of coffee consumption rate with serum 25-hydroxyvitamin D, non-HDL levels, and TC/HDL ratio in females with vitamin D deficiency. Womens Health (Lond). Jan-Dec 2022;18:17455057221112268. https://doi.org/10.1177/17455057221112268
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Mar 26, 2025
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A comparison of the effect of omega-3 alone versus omega-3/Vitamin D3 co-supplementation therapy on 25-hydroxyvitamin D levels in adults with vitamin D deficiency. Pharm Pract (Granada) [Internet]. 2025 Mar. 26 [cited 2025 Apr. 21];23(1):1-9. Available from: https://pharmacypractice.org/index.php/pp/article/view/3050
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How to Cite
1.
A comparison of the effect of omega-3 alone versus omega-3/Vitamin D3 co-supplementation therapy on 25-hydroxyvitamin D levels in adults with vitamin D deficiency. Pharm Pract (Granada) [Internet]. 2025 Mar. 26 [cited 2025 Apr. 21];23(1):1-9. Available from: https://pharmacypractice.org/index.php/pp/article/view/3050