Case 1: Vitamin D for Cardiovascular Health and Cancer Prevention 
Q: HT, a 45-year-old man, is seeking a recommendation for a vitamin D supplement. His brother was recently given a diagnosis of prostate cancer, and HT recalls hearing about the beneficial effects of vitamin D supplementation in preventing cancer, which he is interested in for himself. HT reports that he follows up routinely with his primary care provider and has undergone all appropriate age-related screenings. He is healthy and reports no allergies or use of chronic maintenance medications. What can you suggest regarding vitamin D supplementation?

A: In 2018, a landmark large-scale, placebo-controlled, randomized study seemed to shed additional light on the potential extraskeletal effects of vitamin D. In the VITAL trial, almost 26,000 middle-aged and older adults without a history of cardiovascular disease (CVD), cancer, or other serious conditions were randomized to receive vitamin D3 at a dose of 2000 IU per day and omega-3 fatty acids at a dose of 1000 IU per day for the prevention of cancer and CVD. After a median follow-up of 5 years, investigators found that the use of these supplements did not reduce the occurrence of major cardiovascular events or invasive cancers.1 For HT, this is an opportunity to emphasize and reiterate the importance of adhering to a healthy lifestyle, which includes eating healthy food, not drinking too much alcohol, and not smoking. Encourage him to continue following up with his provider and to undergo indicated health screenings to reduce his risk of cancer and other diseases. If HT is insistent on a recommendation for a supplement, encourage him to follow national dietary guidelines for his age and gender, including evaluating vitamin D intake from food sources, to ensure that he is receiving 600 IU per day.2


Case 2: Health Benefits of Omega-3 Fatty Acid Supplementation 
Q: FS, a 69-year-old woman, has a question about fish oil supplements. She has been taking an omega-3 fish oil supplement for several years, not at the advice of her physician but because she read that it may be beneficial for brain and heart health and could reduce cancer risk. FS has a significant family history for all these conditions, so she wants to make sure that she is doing everything possible to keep herself healthy. She recently came across a report that suggested there might be no benefit to supplementing with the product. FS denies allergies to medications and reports no other significant medical history. What counseling can you provide regarding the benefits of omega-3 fatty acid supplementation, in light of the findings of this recent study?

A: In the VITAL study, mentioned in the previous case, investigators evaluated the effects of omega-3 fatty acid supplements in preventing CVD.1 In the nearly 26,000 patients with an average age of 67 without known CVD enrolled in this study, randomized to receive either 1 g of fish oil (eicosapentaenoic acid plus docosahexaenoic acid) or a placebo daily, a similar number of major cardiovascular events, such as cardiovascular-related death, nonfatal myocardial infarction (MI), and stroke, occurred in patients receiving the supplement compared with the placebo at the mean follow-up of 5.3 years.1 There was a significantly lower incidence of MI in the group receiving the fish oil supplement, but the absolute difference between the groups was small (1.1% vs 1.5%) during the treatment period. Results of an additional trial in patients with diabetes but without CVD randomized to receive 1 g of fish oil capsules or a placebo showed similar outcomes.3 Given these emerging data, FS should be told that the evidence does not support the use of omega-3 fatty acid supplements for preventing cardiovascular events in patients without a history of CVD. Remind her about the importance of routine medical care, and encourage her to follow up with her primary care provider if she thinks that she is experiencing any changes in her health or has any medical complaints.


Case 3: Lung Cancer Risk with B Vitamin Supplementation 
Q: KW, a 62-year-old man, is seeking advice regarding the dietary supplements he takes. For years, at the advice of his wife, he has taken a B vitamin combination each day. KW recalls recently reading that there may be a relationship between B vitamins and the development of lung cancer in men, and he wants to know whether this is a warning he should consider or just media hype. He suffers from other chronic medical conditions and takes several medications and supplements each day, and he would be happy to discontinue this supplement if it is potentially harmful. What suggestions for use of this supplement can you provide?

A : An analysis of the data of more than 77,000 individuals aged 50 to 76 years participating in the previously mentioned VITAL cohort, a study conducted in Washington from 2000 to 2002, was conducted to evaluate the 10-year average daily doses from individual and multivitamin supplements to evaluate the correlation, if any, with development of primary, invasive lung cancer.4 Investigators concluded that although use of supplemental vitamins B6, B12, and folic acid was not associated with lung cancer risk among women, supplementing with vitamins B6 and B12 from individual supplements, not multivitamins, was associated with a 30% to 40% increase in lung cancer risk in men, with men who consume the highest amounts of daily intake of these nutrients having a nearly 2-fold increase in risk and higher risks observed in male smokers.4 Inquire about KW’s smoking history, and encourage him to discuss these findings and the use of the supplements findings with his physician if he has additional questions.


Case 4: Vitamin Supplements for CVD Prevention and Treatment 
Q: FM, a 64-year-old woman, wants to speak to a pharmacist about the use of vitamin supplements to reduce her risk of a heart attack. She has been managing dyslipidemia and hypertension for years but was recently admitted to a local hospital for evaluation of chest pain. After undergoing a cardiac catheterization, FM was instructed to remain compliant with her medications and encouraged to pursue lifestyle modification. However, she wants to know whether, in addition to losing weight and modifying her diet as instructed by her physician, a vitamin supplement can promote heart health. What information can you provide for the use of vitamin supplements to prevent and treat CVD?

A: A recent systematic review and meta-analysis of systematic reviews, meta-analyses, and randomized controlled trials concluded that of the 4 most commonly used supplements (multivitamins, vitamin D, calcium, and vitamin C), supplementation with none of these had a significant effect on cardiovascular outcomes of all-cause mortality.5 Reiterate FM’s physician’s recommendations for dietary modification and weight loss to lower her blood pressure and cholesterol levels, and remind her that dietary sources are best for ensuring optimal daily intake of nutrients and vitamins. For more information about the evidence for the use of supplements for reducing the risk of cardiovascular events, encourage her to speak with her cardiologist or primary care provider.
 
Mary Barna Bridgeman, PharmD, BCPS, BCGP, is a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers University in Piscataway, New Jersey, and an internal medicine clinical pharmacist at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.

Rupal Patel Mansukhani, PharmD, CTTS, FAPhA, is a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers University and a transitions-of-care clinical pharmacist at Morristown Medical Center in New Jersey.


References 
  1. Manson JE, Cook NR, Lee IM, et al; VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44. doi: 10.1056/NEJMoa1809944.
  2. Institute of Medicine, Food and Nutrition Board, Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds. Washington, DC: National Academies Press; 2010.
  3. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects on n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379(16):1540-1550. doi: 10.1056/NEJMoa1804989.
  4. Brasky TM, White E, Chen CL. Long-term, supplemental, one-carbon metabolism-related vitamin B use in relation to lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort. J Clin Oncol. 2017;35(30):3440-3448. doi: 10.1200/JCO.2017.72.7735.
  5. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol. 2018;71(22):2570-2584. doi:10.1016/j.jacc.2018.04.020.