1. ingredients
2. potency
3. quality
4. manufacturing process

In general, however, basic mass-market multiples are often sold at a lower price because they are inferior in one or more of those four basic ways. Typically, they omit mixed carotenoids, bioflavonoids and smaller minerals and nutrients such as vitamin K, boron and iodine. Because they contain fewer ingredients, and often not some of the premier more costly ingredients such as CoQ10, they are less expensive. One of the most striking differences is the amount of individual ingredients. For instance, vitamin D may range from 100 IU to 400 IU; calcium may vary from 200 mg to 500 mg. Taking one capsule/tablet per day may be what is written on the label, but serving sizes may be 2 or 3 capsules in order to get the total on the label. The point is, read the label carefully so you are taking the number of capsules you need to take, in order to get the dose on the label. Many of the vitamins and minerals are available in more than one form and some are more bioavailable than others. Bioavailability is determined by absorption or more efficient use by the body. For instance, calcium carbonate is usually less expensive, but for some people it is constipating and they do better with calcium citrate - this is not necessarily more expensive, but it is a bulkier form of calcium with less elemental calcium per pill, so you have to take more pills to get the dose you have targeted. Many vitamins are synthetic and aren’t available in natural forms. Beta carotene for example comes in a natural or synthetic form and better yet, some multiples contain natural mixed carotenoids and the natural form of other vitamins, which provide additional more potent antioxidant effects. Processing methods also vary, and some of those methods expose the nutrients to greater heat less stable conditions, and use additives and dyes which can render them with less nutritional value.

One capsule/tablet per day mass market multis are usually very low potency, contain the less desired form of the nutrient, omit some important ingredients that would be optimal for a daily vitamin, and contain unnecessary additives. Look for multis where the serving size is 2 or 3 capsules per day, have mixed natural carotenoids, have some of the extras such as bioflavonoids, vitamin K, boron, iodine and then you have to be a bit studious in order to learn about the more bio-available forms of nutrients. The book, Encyclopedia of Nutritional Supplements by Michael Murray, N.D. is an excellent resource for this.

Vitamin D deficiency is associated with increased parathyroid secretion, increased bone turnover, osteoporosis, and increase risk of hip and other fractures. Lower levels of vitamin D as measured in the blood, is also associated with risks of cancers of the colon, breast and ovary in several observational studies. Vitamin D deficiency has other serious implications and has been associated with multiple sclerosis, type-1 diabetes, Chrohn’s disease , and even increases in the risk of hypertension and cardiovascular disease.
Causes of vitamin D deficiency include hereditary disorders, reduced skin synthesis and absorption of vitamin D, and acquired disorders of vitamin D absorption, metabolism and responsiveness.

We get our vitamin D from exposure to sunlight, from our diet and from supplementation. Vitamin D3 is produced in the skin on exposure to ultraviolet radiation, and vitamin D2 is derived from plants and enters our body only through the diet or supplementation. There are two major supplemental forms of vitamin D; vitamin D2 (ergocalciferol) and vitamin D3 (holecalciferol). Vitamin D2 is manufactured through the ultraviolet irradiation of ergosterol from yeast. Vitamin D3 is made through the ultraviolet irradiation of 7-dehydrocholesterol from lanolin. Vitamin D2 is considered to be vegetarian suitable, and vitamin D3 is animal derived, from the lanolin. Both forms are often added to foods such as milk, orange juices, infant formulas, cheeses and breakfast cereals. Natural food sources of vitamin D3 include salmon, sardines, mackerel, tuna, shiitake mushrooms, egg yolks, cod liver oil and exposure to sunlight. Both vitamin D2 and vitamin D3 are available in over the counter supplements, including low doses, and moderately higher doses, typically not more than 5,000 IU. High and higher doses of vitamin D2 are available by prescription.

The back story on whether or not vitamin D2 and vitamin D3 are equally effective, goes back to studies in the 1930s where they were assumed to be equally effective in humans. Over time, human studies comparing the increase in blood levels of vitamin D with the supplementation of vitamin D2 vs vitamin D3 have been inconsistent in their results and few in number. They have also been wrought with problems in small sample sizes, lack of vitamin D stability of the products used, wide variations in the seasons the blood was drawn (serum levels of vitamin D are naturally higher in the sunnier months), variable intestinal absorption amongst individuals, variable baseline serum levels of vitamin D, previous history of vitamin D supplementation and variations in age (older people have less vitamin D absorption). While common thought is that vitamin D2 is about 30% less potent than vitamin D3, these variables in the studies, make it extremely difficult to make comparisons and draw accurate conclusions. One small study done in 1998 did demonstrate that vitamin D3 yielded a small increase in serum 25-hydroxyvitamin D over the vitamin D2. A study of 30 men in 2004, between the ages of 20 and 61, demonstrated that the rise in blood levels within the first few days of receiving a single high dose was the same for both forms, indicating equivalent absorption. However, the vitamin D3 treated individuals had a continued rise over two weeks and peaked at 2 weeks, while the vitamin D2 treated men, had a decline to their baseline, by day 14. One might conclude from these two well designed studies, that the rise in serum levels with vitamin D3 might be only a very small amount, as in the first study. Or, rather than give one dose to last 2 or more weeks where there was a greater effect with vitamin D3, as in the second, this same study showed that within the first 3 days of either form, the rise in blood levels, was the same, indicating that a daily dose of either form of vitamin D would be equivalent.

The newest study addressing this question, challenges the long held belief that vitamin D2 is less potent or less effective than vitamin D3 in raising and maintaining blood levels. This was a randomized, placebo-controlled, double-blinded study of healthy individuals ages 18-84 years who received either placebo, 1,000 IU of vitamin D3, 1,000 IU of vitamin D2, or 500 IU of vitamin D2 plus 500 IU of vitamin D3 daily for 11 weeks at the end of the winter. Sixty percent of the study subjects were vitamin D deficient at the start of the study (< 20 ng/ml). This three month study of 68 individuals found that supplementation with both forms produced similar results. Neither 1,000 IU of vitamin D2 or vitamin D3 raised 25-hydroxyvitamin D levels in vitamin D deficient subjects to a level above 30 ng/ml. The authors concluded that vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

My main point in this article is not to prove that the vegetarian supplementation of vitamin D2 is as potent as the non-vegetarian supplement vitamin D3, but rather, that we cannot state with reasonable certainty that D3 is 30% more potent, as is generally thought. Vegetarians may find some comfort in this article about vitamin D2 and vitamin D3 yielding similar results, at least when taken daily. If not, then the most we could assert, is that we may need a one third higher dose of vitamin D2 to yield the same results.

References

• MacLaughlin J, Holick M. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985; 76: 1536-1538.
• Parfitt A. Osteomalacia nd related disorders. In: Avioli L, Krane S, eds. Metabolic bone disease and clinically related disorders. 2nd ed. Philadelphia: WB Saunders; 329-396.
• Trivedi D, Doll R, Khaw K. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ 2003; 326: 469- 474.
• Garland C, Garland F, Gorham E, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006; 96: 252-261.
• Cantorna M, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80: Suppl 6: 1717S-1720S.
• Ponsonby A-L, McMichael A, van der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological reearch. Toxicology 2002; 181-182:71-78.
• Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol 2006; 92: 39-48.
• Rostand S. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension 1997; 30: 150-6.
• Trang H, Cole D, Rubin L, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2.
• Armas L, Hollis B, Heaney R. Vitamin D2 ismuch less effective than vitamin D3 in humans. J Clinical Endocrinology and Metabolism. 2004;89(11): 5387-5391.
• Holick M, Biancuzzo R, Chen T, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 2007; Dec 18.

Fifty women developed cancers other than skin cancer. The risk for cancer in the calcium-plus vitamin-D group was less than half that in the placebo group (RR 0.4; P=0.013). The calcium only group had no statistically significant risk reduction. Researchers adjusted for the possibility that cancers detected during the first year of the study, had been present but silent at baseline, and analyzed these separately. Relative risk for cancer in the calcium/vitamin D group was lower than in the placebo control subjects 0.2 (P< 0.005), and the risk reduction for the calcium only group was not statistically significant.

Women in the calcium plus vitamin D group had higher serum vitamin D levels that correlated with lower cancer risk, both at baseline and at one year. Adherence to the study doses was 86%.

Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nut 2007; Jun;85(6):1586-1591

Commentary: The only other randomized trial of vitamin D and cancer was the Women’s Health Initiative, which used a lower dose of vitamin D (400 IU) and women with a lower baseline vitamin D status. The WHI reported no significant effect of the vitamin D intervention on colorectal cancer incidence but did observe a significant inverse relation between baseline vitamin D levels and cancer risk, as in this study. It’s reassuring to see that the benefits of higher than recommended dosing of vitamin D is catching on. It is estimated that about 60% of women in the U.S. are vitamin D deficient, no what part of the country they live in. The current adult daily recommendations for vitamin D in women 51 to 70 is
400 IU -800 IU per day. Supplement doses up to 2000 IU are considered safe and to be without significant risk for adverse events. Many practitioners are advising even higher doses, but I would recommend this only after assessment for medical need, serum testing, and evaluation for risk of side effects.

Calcium and Vitamin D Intake and Risk for Breast Cancer

The relationship between vitamin D and breast cancer was prospectively assessed among 10,000 premenopausal and 20,000 postmenopausal women who were enrolled in the Women’s Health Study. Intake of calcium and vitamin D was determined from self-reported questionnaires about diet and vitamin use.

During an average follow-up of 10 years, the overall incidence of invasive breast cancer was 2.6% among premenopausal women and 3.6% among postmenopausal women. Among premenopausal women, the hazard ratio for developing breast cancer was 0.61 for women in the highest versus lowest quintiles of calcium use and 0.65 for vitamin D intake. No benefit was seen for these nutrient intakes and breast cancer risk in postmenopausal women.

Lin J et al. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 2007, May 28; 167(10):1050-1059.

Commentary: This is a very large, prospective study, which once again demonstrates important findings for vitamin D, at least for premenopausal women. A higher intake of calcium and vitamin D was associated with a lower risk for breast cancer among premenopausal women, but not for postmenopausal women. While the hazard ratio was large, the absolute reduction in risk was small. Being a population based study using only self-reported questionnaires, the usefulness of the findings in this study are limited, especially since the amount of vitamin D and calcium was recorded only once at baseline. In addition, there could easily be other variables that explain the findings. Nonetheless, it supports the trend to advise women about adequate intakes of calcium and vitamin D, both in the diet and in supplement form.

Lappe J, et al. Â Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Â Am J Clin Nut 2007; une 85: 1586-1591

Lin J et al.  Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med 2007, May 28; 167:1050-1059.