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Woman showing fish oil that is linked to reducing disease risks

Update on Vitamin D and Fish Oil Supplementation

Higher potencies of omega-3s and vitamin D, combined with blood testing, are demonstrating remarkable health benefits.

Scientifically reviewed by:  Julia Dosik, MPH, in October 2024. Written by: Harry Fulton.

Vitamin D and fish oil are some of today’s most popular dietary supplements.

One reason many people take them is widespread news coverage showing marked reductions of degenerative disorders in response to higher intake of these nutrients.

Since it is no longer “news” that fish oil and vitamin D favorably influence human health, some media sources run tabloid-like headlines that often misinterpret findings from clinical trials.

A clinical trial called VITAL used modest potencies of EPA/DHA from fish oil and vitamin D3 that did not meet challenging primary clinical endpoints. This caused many media sources to proclaim there to be no value in supplementing with these low-cost nutrients.

That’s regrettable because people who need them the most, i.e. those living in difficult socioeconomic circumstances, are often more adversely impacted by a lack of these kinds of protective nutrients.

This article describes studies in which higher potencies of omega-3s or vitamin D have demonstrated remarkable health benefits.

Vitamin D and Cancer

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An explosion of research in recent decades has demonstrated that vitamin D impacts almost every aspect of health, including protection from cancer and cardiovascular disease.

As new studies have been published, many experts have revised their recommendations upward for daily vitamin D intake and blood levels.

Many now suggest that a target 25-hydroxyvitamin D blood level of 50 ng/mL to 80 ng/mL is ideal for optimal protection from cancer. This level is far above what aging individuals obtain from sun exposure and dietary sources.

Recommendations for higher vitamin D target levels are based on a growing body of evidence that individuals with low levels of vitamin D are at the greatest risk of developing cancer and dying from the disease—while those with the highest levels have reduced cancer incidence.

Vitamin D deficient women have been found to have greater odds of developing breast cancer and a 253% increase in risk for colon cancer, compared to those with the highest vitamin D levels.1,2 One study found that higher levels of vitamin D in men prior to a prostate cancer diagnosis were associated with improved survival rates.3

Another study evaluated individuals being treated for advanced colorectal cancer.4 During chemotherapy treatment, these patients were randomized to either receive a low (standard) dose of vitamin D (400 IU per day) or a high dose (starting at 8,000 IU per day and later decreasing to 4,000 IU per day).

The higher dose resulted in better outcomes. During the follow-up period, the individuals receiving higher doses were 36% less likely to suffer from cancer progression or to die, than those given the lower (400 IU/day) dose.

These studies and others suggest a dose-response relationship: The higher the level of vitamin D, the lower the risk of cancer or dying from cancer.

One study found a 12% reduction in mortality from breast cancer for every 8 ng/mL increase in vitamin D blood level.5

Other studies have estimated a 10% decrease in death due to colon cancer for every 8 ng/mL increase in vitamin D. Overall risk of cancer was as much as 35% lower in those with 25-hydroxyvitamin D levels of 55 ng/mL or higher.6,7

Several types of studies, including geographical ecological studies, observational studies, laboratory studies of mechanisms, and clinical trials have tested the vitamin D and cancer-prevention connection.

Some clinical trials reveal that even low-dose vitamin D3 may reduce cancer risk.

One study published in The American Journal of Clinical Nutrition evaluated the impact of vitamin D3 and calcium supplementation on cancer risk reduction in postmenopausal women.

The study found that improving calcium and vitamin D status by supplementation of 1,100 IU/day of vitamin D3 plus 1,450 mg/day of calcium reduced all-cancer risk.8

Another study involving more than 36,000 postmenopausal women found that supplementation with 1,000 mg/day of calcium and 400 IU/day of vitamin D significantly decreased the risk of total, breast, and invasive cancers by 14% to 20%.9

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What You Need to Know

Vitamin D and Fish Oil Update

  • The health benefits of omega-3s and vitamin D supplementation are well documented.

  • Research shows that vitamin D and omega-3s offer protection against cancer and cardiovascular disease.

  • Life Extension recommends doses of 5,000 IU to 8,000 IU of vitamin D and 2,400 mg of EPA/DHA from fish oil daily to maintain optimal levels. Regular blood testing is important to guide adjustments to these doses to achieve the maximum benefits.

  • Experts suggest maintaining blood levels between 50 ng/mL and 80 ng/mL for vitamin D and an omega-3 index of 8% to 12%.

Vitamin D and Cardiovascular Disease

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A similar link between vitamin D levels and cardiovascular disease has been demonstrated in medical research.

Several studies have shown that lower vitamin D levels are associated with high blood pressure, elevated blood glucose, atherosclerotic plaque in blood vessels, arterial stiffness, and higher rates of cardiovascular events.10-19

In humans, vitamin D supplementation can reduce some of these markers of blood vessel disease. For example, 4,000 IU daily was shown to reduce arterial stiffness.15,19

One study evaluated the association of vitamin D and strokes, which often result from cardiovascular disease. Vitamin D status was measured in 3,316 patients with evidence of blood vessel disease who were followed for almost eight years. What scientists found was a dramatic increase in the number of fatal strokes for every incremental decrease in vitamin D blood level.20

Omega-3 Fatty Acids and Cardiovascular Disease

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Several studies have shown a close link between high levels of omega-3 fatty acids from fish oil and protection from aspects of cardiovascular disease.

Like vitamin D, the highest blood levels of omega-3s have been shown to be the most protective. For example, individuals with the highest omega-3 blood levels are 50% less likely to suffer from congestive heart failure than those with low levels.21 Overall survival in patients with existing heart failure is 35% better in those with higher omega-3 levels.22

A study in Atherosclerosis found that an omega-3 index of 8% or higher, far above the 4% achieved by the dosing in the VITAL trial, was protective against fatal heart disease.23 Compared to those with an index below 4%, these optimal levels (8% and higher) reduced risk of death from coronary heart disease by about 30%.

Another study, published in the journal Preventive Medicine, found that the greatest protection from death by cardiovascular causes was found in individuals with an omega-3 index greater than or equal to 8%.24

Moreover, studies with long follow-up periods have found that an omega-3 index of 8% or higher reduces the risk of death from any cause, with a 7% lower overall risk of dying gained by each additional 200 mg of fish oil consumed per day.25,26

In one study, researchers enrolled patients at high risk of experiencing cardiovascular events. Those who were randomized to receive 2,000 mg of a supplement containing 930 mg of EPA and 750 mg of DHA (two omega-3 fatty acids) had a 70% reduction in heart attacks, and a 60% decrease in other coronary events.27

Several other studies using daily doses of 2,000 mg to 4,000 mg of fish oil have also shown benefits for various cardiovascular disease outcomes.28-30

It is important to note that comprehensive management of cardiovascular disease risk requires a comprehensive assessment of risk factors beyond cholesterol and blood pressure.

A paradigm shift is crucially needed to move away from focusing on a single number for LDL-cholesterol to focusing on the complete patient, by taking into account a range of biomarkers that can yield additional insight.

Although lowering low-density lipoprotein cholesterol (LDL-C) is a primary target for cardiovascular disease risk reduction, lifestyle related factors, such as tobacco use, obesity and sedentary routines, are also very important.31

In addition, many other risk factors, such as insulin resistance, hormonal imbalances, hypercoagulable states, hyperhomocysteinemia, vascular inflammation, hyperglycemia, and others also play important roles.32

Nutrients like magnesium, CoQ10, fish oil omega-3s, vitamin K2, and others also play an important, underappreciated role in cardiovascular health.30,33-48

Further, advanced testing of lipoprotein fractionation identifies the full spectrum of lipoprotein particles, along with direct quantification of particles in each lipoprotein subclass fraction.

The sub-particles of LDL have a set of distinct properties including size and density. The small LDL particles are much more strongly related to risk than the larger LDL particles. Advanced lipoprotein subclass testing (such as the NMR blood test) provides additional information not otherwise identified through routine lipid testing for total cholesterol, LDL, HDL and triglycerides.

Omega-3 Fatty Acids and Cancer

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Fish oil consumption, both from the diet and supplementation, has a profound effect on cancer. It appears to reduce the abnormal changes in cells that can lead to tumors, and to reduce the growth and aggressiveness of existing cancers.

Research has even found that factors which predispose cells to tumor growth are reduced with omega-3 supplementation. In one trial, 4,000 mg of an omega-3 supplement each day protected the skin from the harmful effects of solar radiation.49 The damage caused by sun exposure was reduced, including a 36% improvement in sunburn protection and significant reduction of DNA damage, which can contribute to skin cancer.

In another study, 2,000 mg of omega-3s daily reduced the number of precancerous cells on colonoscopy inspection.50 This indicates a minimized risk for colon cancer.

Another clinical trial used a dose of 5,000 mg of fish oil daily in men with prostate cancer, leading up to surgery.51 When the patients underwent surgery, pathologists found that those men who received fish oil supplementation demonstrated a significant reduction in proliferation of cancer cells. Less aggressive tumors typically equate to better control with treatment—and better long-term survival.

Omega-3 fatty acids also help support treatment for cancer. Studies of lung cancer patients found that supplementation with fish oil prevented some adverse effects associated with cancer treatment, such as weight loss, and boosted the response of the cancer to chemotherapy.52,53

Various animal and human studies show that omega-3s are protective against cancer, improve response to cancer treatment, and even reduce cancer relapse after treatment.54-56

The benefits of vitamin D and omega-3 fatty acids discussed are just a sampling of those related to cardiovascular disease and cancer. Additionally, these nutrients are beneficial for brain health and cognition, eyesight, metabolic health, overall longevity, and more.

Summary

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Research has shown that vitamin D and omega-3s impact almost every aspect of health, including protection from cancer and cardiovascular disease.

Life Extension recommends doses of 5,000 IU to 8,000 IU of vitamin D and 2,400 mg of EPA/DHA from fish oil daily to maintain optimal levels. Regular blood testing is important to guide adjustments to these doses to achieve the maximum benefits.

Experts suggest maintaining blood levels between 50 ng/mL and 80 ng/mL for vitamin D and an omega-3 index of 8% to 12%.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Abbas S, Linseisen J, Slanger T, et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer--results of a large case-control study. Carcinogenesis. 2008 Jan;29(1):93-9.
  2. Holick MF. Vitamin D and sunlight: strategies for cancer prevention and other health benefits. Clin J Am Soc Nephrol. 2008 Sep;3(5):1548-54.
  3. Li H, Stampfer MJ, Hollis JB, et al. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007 Mar;4(3):e103.
  4. Ng K, Nimeiri HS, McCleary NJ, et al. Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial. JAMA. 2019 Apr 9;321(14):1370-9.
  5. Hu K, Callen DF, Li J, et al. Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies. Integr Cancer Ther. 2018 Jun;17(2):217-25.
  6. Ekmekcioglu C, Haluza D, Kundi M. 25-Hydroxyvitamin D Status and Risk for Colorectal Cancer and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Epidemiological Studies. Int J Environ Res Public Health. 2017 Jan 28;14(2).
  7. Maalmi H, Ordonez-Mena JM, Schottker B, et al. Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies. Eur J Cancer. 2014 May;50(8):1510-21.
  8. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91.
  9. Bolland MJ, Grey A, Gamble GD, et al. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011 Oct;94(4):1144-9.
  10. Bennett AL, Lavie CJ. Vitamin D Metabolism and the Implications for Atherosclerosis. Adv Exp Med Biol. 2017;996:185-92.
  11. Chen FH, Liu T, Xu L, et al. Association of Serum Vitamin D Level and Carotid Atherosclerosis: A Systematic Review and Meta-analysis. J Ultrasound Med. 2018 Jun;37(6):1293-303.
  12. Fondjo LA, Sakyi SA, Owiredu W, et al. Evaluating Vitamin D Status in Pre- and Postmenopausal Type 2 Diabetics and Its Association with Glucose Homeostasis. Biomed Res Int. 2018;2018:9369282.
  13. Grubler MR, Marz W, Pilz S, et al. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Rev Endocr Metab Disord. 2017 Jun;18(2):259-72.
  14. McGreevy C, Barry M, Davenport C, et al. The effect of vitamin D supplementation on arterial stiffness in an elderly community-based population. J Am Soc Hypertens. 2015 Mar;9(3):176-83.
  15. Raed A, Bhagatwala J, Zhu H, et al. Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial. PLoS One. 2017;12(12):e0188424.
  16. Schottker B, Haug U, Schomburg L, et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr. 2013 Apr;97(4):782-93.
  17. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014 Sep;2(9):719-29.
  18. Weng S, Sprague JE, Oh J, et al. Vitamin D deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One. 2013;8(1):e54625.
  19. Zaleski A, Panza G, Swales H, et al. High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency. Dis Markers. 2015;2015:918968.
  20. Pilz S, Dobnig H, Fischer JE, et al. Low vitamin d levels predict stroke in patients referred to coronary angiography. Stroke. 2008 Sep;39(9):2611-3.
  21. Mozaffarian D, Lemaitre RN, King IB, et al. Circulating long-chain omega-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study: a cohort study. Ann Intern Med. 2011 Aug 2;155(3):160-70.
  22. Jiang W, Oken H, Fiuzat M, et al. Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart failure and major depressive disorder. J Cardiovasc Transl Res. 2012 Feb;5(1):92-9.
  23. Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies. Atherosclerosis. 2017 Jul;262:51-4.
  24. Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004 Jul;39(1):212-20.
  25. Harris WS, Luo J, Pottala JV, et al. Red blood cell polyunsaturated fatty acids and mortality in the Women’s Health Initiative Memory Study. J Clin Lipidol. 2017 Jan - Feb;11(1):250-9 e5.
  26. Wan Y, Zheng J, Wang F, et al. Fish, long chain omega-3 polyunsaturated fatty acids consumption, and risk of all-cause mortality: a systematic review and dose-response meta-analysis from 23 independent prospective cohort studies. Asia Pac J Clin Nutr. 2017 20170813;26(5):939-56.
  27. Svensson M, Schmidt EB, Jorgensen KA, et al. N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin J Am Soc Nephrol. 2006 Jul;1(4):780-6.
  28. Koh KK, Quon MJ, Shin KC, et al. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis. 2012 Feb;220(2):537-44.
  29. Nodari S, Triggiani M, Campia U, et al. n-3 polyunsaturated fatty acids in the prevention of atrial fibrillation recurrences after electrical cardioversion: a prospective, randomized study. Circulation. 2011 Sep 6;124(10):1100-6.
  30. Moertl D, Hammer A, Steiner S, et al. Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study. Am Heart J. 2011 May;161(5):915 e1-9.
  31. Available at: https://emedicine.medscape.com/article/2500031-overview#showall. Accessed August 28, 2019.
  32. Fonseca V, Desouza C, Asnani S, et al. Nontraditional risk factors for cardiovascular disease in diabetes. Endocr Rev. 2004 Feb;25(1):153-75.
  33. Knapen MH, Braam LA, Drummen NE, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44.
  34. Baggio E, Gandini R, Plancher AC, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med. 1994;15 Suppl:s287-94.
  35. Langsjoen PH, Langsjoen AM. Coenzyme Q10 in cardiovascular disease with emphasis on heart failure and myocardial ischaemia. The Asia Pacific Heart Journal. 1998 1998/12/01/;7(3):160-8.
  36. Langsjoen PH, Langsjoen AM. Supplemental ubiquinol in patients with advanced congestive heart failure. Biofactors. 2008;32(1-4):119-28.
  37. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014 Dec;2(6):641-9.
  38. Pepe S, Marasco SF, Haas SJ, et al. Coenzyme Q10 in cardiovascular disease. Mitochondrion. 2007 Jun;7 Suppl:S154-67.
  39. Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006 Aug;12(6):464-72.
  40. Singh RB, Wander GS, Rastogi A, et al. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998 Sep;12(4):347-53.
  41. Douban S, Brodsky MA, Whang DD, et al. Significance of magnesium in congestive heart failure. Am Heart J. 1996 Sep;132(3):664-71.
  42. Grober U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226.
  43. Shechter M. Magnesium and cardiovascular system. Magnes Res. 2010 Jun;23(2):60-72.
  44. Heydari B, Abdullah S, Pottala JV, et al. Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial. Circulation. 2016 Aug 2;134(5):378-91.
  45. Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol. 2009 Jul;32(7):365-72.
  46. Nodari S, Triggiani M, Campia U, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011 Feb 15;57(7):870-9.
  47. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q(1)(0) supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013 Feb;97(2):268-75.
  48. Belardinelli R, Mucaj A, Lacalaprice F, et al. Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure. Biofactors. 2005;25(1-4):137-45.
  49. Rhodes LE, Shahbakhti H, Azurdia RM, et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis. 2003 May;24(5):919-25.
  50. Courtney ED, Matthews S, Finlayson C, et al. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis. 2007 Jul;22(7):765-76.
  51. Aronson WJ, Kobayashi N, Barnard RJ, et al. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (Phila). 2011 Dec;4(12):2062-71.
  52. Murphy RA, Mourtzakis M, Chu QS, et al. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011 Apr 15;117(8):1775-82.
  53. Murphy RA, Mourtzakis M, Chu QS, et al. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011 Aug 15;117(16):3774-80.
  54. Chagas TR, Borges DS, de Oliveira PF, et al. Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial. J Hum Nutr Diet. 2017 Dec;30(6):681-92.
  55. Molfino A, Amabile MI, Monti M, et al. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer. Int J Mol Sci. 2016 Apr 5;17(4):505.
  56. Park M, Kim H. Anti-cancer Mechanism of Docosahexaenoic Acid in Pancreatic Carcinogenesis: A Mini-review. J Cancer Prev. 2017 Mar;22(1):1-5.