What is the role of multivitamins (MVs) in medical treatment?

Role of Multivitamins in Medicine

Multivitamins should NOT be routinely recommended for the primary prevention of cardiovascular disease or cancer in healthy adults, as they provide no mortality benefit and no consistent cardiovascular or cancer prevention benefit in the general population. 1, 2

General Population: No Routine Recommendation

The U.S. Preventive Services Task Force concludes there is insufficient evidence to determine any balance of benefits and harms of multivitamin supplementation for preventing cardiovascular disease or cancer in healthy adults. 1, 2

Key Evidence Against Routine Use:

• No mortality benefit: Multiple randomized controlled trials found no effect on all-cause mortality with multivitamin supplementation. 1, 2

• No cardiovascular benefit: Studies consistently showed no effect on cardiovascular disease incidence or events. 1, 2

• Minimal cancer benefit: Two trials (Physicians' Health Study II and SU.VI.MAX) showed a modest decrease in cancer incidence in men only (pooled relative risk 0.93,95% CI 0.87-0.99), but not in women, and these findings are not generalizable due to homogeneous study populations (primarily older white male physicians). 1, 2

• Better alternatives exist: Adequate nutrition through a diet rich in fruits, vegetables, whole grains, fat-free and low-fat dairy products, and seafood has been associated with reduced risk for cardiovascular disease and cancer. 1

Specific Vitamins to AVOID

β-carotene and vitamin E should NOT be used for disease prevention in healthy adults. 2

β-Carotene (Grade D Recommendation - Recommend Against):

• Increases lung cancer risk in smokers and those with asbestos exposure, with increased lung cancer mortality demonstrated in the ATBC and CARET trials. 1, 2
• This represents one of the few clear harms documented with vitamin supplementation. 1

Vitamin E:

• Provides no net benefit for cardiovascular disease or cancer prevention. 1, 2
• One trial found increased risk for hemorrhagic stroke in the intervention group. 1
• Mixed results for prostate cancer, with SELECT trial showing increased risk after extended follow-up. 1

Vitamin A:

• High-dose vitamin A can reduce bone mineral density at moderate doses and is hepatotoxic and teratogenic at high doses. 2
• Increased risk for hip fractures observed in postmenopausal women. 1

Populations That MAY Benefit from Supplementation

Older Adults:

A daily multivitamin may be appropriate for older adults, particularly those with reduced energy intake. 2

Specific recommendations for older adults include:

• Vitamin D: 15 μg (600 IU) daily supplementation recommended. 2
• Calcium: At least 1,200 mg daily from diet or supplements. 2
• Vitamin B12: 4-6 μg/day due to high prevalence of deficiency in this population. 2

Cancer Patients:

For cancer patients, multivitamin-multimineral supplements in physiological doses (approximately equal to the RDA) are useful and safe, including during chemo- and radiation therapy. 1

• This recommendation applies specifically to cancer patients with restricted dietary patterns who are at risk for micronutrient deficiency. 1
• High-dose micronutrients should be avoided in the absence of specific deficiencies. 1
• Vitamin D deficiency is frequently observed in cancer patients and has been associated with cancer incidence and prognosis, though supplementation to normalize levels has not been proven to improve prognosis. 1

Pregnant Women:

Women who are planning to or may become pregnant should receive daily folic acid supplementation to help prevent neural tube defects. 1

Older Persons at Risk for Falls:

Vitamin D supplements are recommended for older persons at risk for falling. 1

Important Safety Considerations and Pitfalls

Fat-Soluble Vitamin Accumulation:

• Fat-soluble vitamins (A, D, E, K) accumulate over time, and lifetime effects of high doses must be considered. 2
• Exceeding upper intake levels of vitamins A and D can have known harms above tolerable upper limits. 2

Long-Term Safety:

• Long-term use of multivitamins not exceeding the upper limit of recommended intakes has been determined to be safe in healthy adults. 3
• No consistent adverse effects of multivitamin and mineral supplements were evident in systematic reviews. 4

Common Pitfall - Assuming Supplements Replace Diet:

• Multivitamins should never be considered a substitute for a balanced diet emphasizing fruits, vegetables, and whole grains. 5
• Individuals who use dietary supplements generally report higher dietary nutrient intakes and healthier diets, making it difficult to attribute health benefits solely to supplementation. 6

Clinical Approach Algorithm

Step 1: Assess Risk Factors for Deficiency

Screen for specific deficiency risk factors:

• Age >65 years 2
• Restrictive diets 2
• Malabsorption conditions 2
• Medications like proton pump inhibitors 2
• Pregnancy or planning pregnancy 1
• Cancer diagnosis with restricted dietary intake 1

Step 2: Emphasize Dietary Sources First

• Recommend nutrients come primarily from foods rich in fruits, vegetables, whole grains, fat-free and low-fat dairy products, and seafood. 1
• Explain that adequate nutrition through diet has been associated with reduced risk for cardiovascular disease and cancer. 1

Step 3: If Supplementation is Chosen

For patients who choose to take multivitamins despite lack of evidence:

• There is little reason to discourage use, except for β-carotene in smokers. 2
• Recommend adherence to Dietary Reference Intakes and avoid doses greatly exceeding Recommended Dietary Allowance. 2
• Ensure formulations do not exceed upper intake levels for fat-soluble vitamins. 2

Step 4: Target Specific Populations

For older adults with reduced energy intake:

• Consider multivitamin with vitamin D (600 IU), calcium (1,200 mg), and vitamin B12 (4-6 μg/day). 2

For cancer patients with restricted dietary patterns:

• Recommend multivitamin-multimineral supplement in physiological doses approximately equal to RDA. 1
• Avoid high-dose micronutrients unless specific deficiency documented. 1

For pregnant women or those planning pregnancy:

• Prescribe daily folic acid supplementation. 1

Nuances in the Evidence

Divergent Findings by Sex:

The cancer prevention benefit observed in two trials (Physicians' Health Study II and SU.VI.MAX) was limited to men only, with no effect in women. 1 This sex-specific finding, combined with the homogeneous study populations, makes extrapolating these findings to the general population difficult and does not support routine recommendation. 1

Quality of Evidence:

The USPSTF notes that the paucity of studies and general lack of effect of any single nutrient or nutrient pair makes it difficult to draw meaningful conclusions without a coordinated research effort. 1 There is a general lack of standardized methods to determine relevant serum nutrient levels or agreement on thresholds for sufficiency and insufficiency. 1

Consensus Among Major Organizations:

• The American Cancer Society found that current evidence does not support the use of dietary supplements for the prevention of cancer. 1
• The American Heart Association recommends that healthy persons receive adequate nutrients by eating a variety of foods rather than supplementation. 1
• The Academy of Nutrition and Dietetics noted that although multivitamin supplements may be useful in meeting recommended levels of some nutrients, there is no evidence that they are effective in preventing chronic disease. 1