“Multivitamins”. What are they?

August 5. 2024

“Multivitamins have no effect”, “Multivitamins do not prolong life”, Multivitamins are a waste of money” and other similar headlines we have now seen in the past weeks in various
Danish newspapers and other media.

The observational study
All these headlines are based on an observational study from the United States that has been published June 26. this year.

An observational study is a study in which researchers “observe” different data, such as cohort studies and cross-sectional studies.

Observational studies are a relatively cheap research method because they do not require an intervention into the behavior of an experimental group. More simply, they involve observing how the selected data are distributed in relation to a certain behaviour such as taking a supplement and a certain outcome such as quality of life or mortality.

In the current study (Multivitamin use and mortality risk in 3 prospective US cohorts, JAMA Network Open. 2024;7(6):e2418729), data from three such observational studies were used. From the data, it was concluded that there is no significant effect of multivitamin use on life expectancy, which is the factor that has been focused on in the study.

Strangely enough, the focus is on life expectancy even though the authors themselves write in the introduction that the population’s motivation for taking multivitamins is to prevent disease.

But the incidence of disease does not appear in the data we see presented in the article in JAMA (Journal of the American Medical Association). The authors focus only on the length of life. They actually use the word mortality, but it is rather meaningless, since the mortality is approx.100% for us humans.

The investigation has been heavily hyped by the mainstream media, so we have to take it seriously., We need to clear away the worst misunderstandings.

The strange thing is that if this study had shown that multivitamins were healthy and good for us, it would not have been accepted for publication precisely because it was an observational study. Because such observational studies rank low on the scale of evidence in scientific studies.

The reason is that observational studies have quite a few sources of error, sources of bias. The data in the study come from people themselves, who have answered the questions that the researchers have asked. Moreover, the study is neither half, nor fully or double blinded, so it requires extreme objectivity from researchers. But for now, let’s ignore study quality, bias and the usual researcher bias when we talk about vitamins.

Let’s look at what these “multivitamin pills” really are.

When I write like that, it’s because these standard multivitamin pills from the supermarket are also not my cup of tea. Most multivitamin pills contain a wide range of vitamins and minerals, typically 100% of the recommended daily dose, in Denmark also called the RI (reference intake). This RI dose is far too small for some substances (vitamin C, vitamin D, selenium, etc.), while, especially for iron, it is far too large. Other ”multivitamins contain largely unabsorbable salts of some of the substances (magnesium, selenium etc.)

Briefly about iron
Those who have heard my lectures for the past 30 years also know that you should not buy vitamin pills with iron, unless you have been diagnosed with iron deficiency or are pregnant in the last trimester.

The body normally loses about 2 mg of iron per day. Since most multivitamin pills contain about 14 mg of iron, there is a theoretical net surplus of 12 mg of iron each day. And this iron accumulates in a protein, the phase reactant ferritin.

In this way, over the years, simply by taking multivitamin pills, you can build up a supply of iron in this ferritin. Iron is one of the most powerful catalysts for the formation of free radicals (ROS), which, in excess, can cause great damage to cell membranes and DNA in particular.

If a small child is brought to the emergency room because he has eaten a whole jar of ordinary multivitamin pills from the supermarket, then the doctor worries primarily about one thing; it is the intake of the large amount of iron.

Iron is easy and quick to raise the level in the body if you lack it, but incredibly difficult to get rid of if you have have too much. It must be done with intravenous treatment with substances such as Desferoxamine or EDTA, both of which bind iron. But it is difficult and slow. The age-old bloodletting method is almost faster.

Serum Ferritin is an important marker, and if it is above 200 µg/l, there is an increased risk of cardiac vascular diseases and cancer. So you have to be careful with iron. It is a double-edged sword.

Summa summarum: Never take multivitamin pills with iron, unless you have been diagnosed with iron deficiency in the form of low S-Ferritin.

Back to the study
When you consider that a cohort of people has been taking these multivitamin pills for years, then you suspect that they have obtained both good and bad ingredients. Honestly, it is completely impossible to come up with a qualified assessment when you (and the researchers) really have no idea what the people answering questionnaires have consumed.

I could easily formulate a multivitamin pill that mainly has a negative effect on the body. The pill will be cheap. With sufficient advertising money, it would probably be sold by the large supermarket chains, which look at price, discounts and shelf life.

I could use sodium selenite as the selenium. It is quite cheap, and I could declare it as selenium. It just that it’s hardly absorbed into the body. So the effect that can halve the incidence of heart disease and death, well, it will not occur.

I could use chromium chloride as chromium. It is quite cheap, but it is also quite inactive in comparison to chromium yeast, in which chromium chloride is converted to GTF chromium (glucose tolerance factor), which stabilizes blood sugar. Chromium chloride does not have this effect, but can be declared as chromium on the packaging, and then most people think that they get enough.

Every single one of the ingredients found in multivitamin pills can be declared in this way, even if the ingredient is in a (often cheap) form that has no positive biological effect. As I wrote above, you can easily construct a very cheap pill with a fine declaration, but without any kind of positive effect.

This is not to say that there are only such “junk pills” in the study. I just want to illustrate that when you have not defined the quality or content of what the study participants have actually eaten, it is more than difficult to form an overview of something as varied as the term “multivitamin pills”.

And when the product being studied is not a well-defined product, it is, to put it mildly, frivolous to conclude anything health related from the given data, and the authors are content with concluding, that they saw no difference in mortality risk in the two groups.

Let me end by saying that vitamins and minerals rarely help anything.
– You just mustn’t lack them.

The most important thing is, of course, a healthy diet, and where this fails in terms of content, you should supplement with vitamins and minerals of good quality.

Take care of yourself and others.

Claus Hancke
Specialist in general medicine

Iron, Research references

  1. Allen, LH. Pregnancy and iron deficiency. Unresolved issues. Nutr Rev 1997; 55: 91-100.
  2. Anonymous. Vitamin A deficiency and anemia. Nutr Rev 1979; 37: 38-40.
  3. Anonymous. Vitamin A deficiency and iron nutriture. Nutr Rev 1984; 42: 167-168.
  4. Ballin A, Berar M, Rubinstein U, et al. Iron state in female adolescents. Am J Dis Child 146(7): 803-5, 1992.
  5. Ballott DE, MacPhail AP, Bothwell TH et al. Fortification of curry powder with NaFe(111) EDTA in an iron-deficient population. Initial survey of iron status. Am J Clin Nutr 1989; 49: 156-161.
  6. Bates CJ et al. Vitamins, iron, and physical work. Lancet ii: 313-14, 1989.
  7. Beard, JL, Dawson H, Pinero, DJ. Iron metabolism. A comprehensive review. Nutr Rev 1996; 54: 295-317.
  8. Beutler E, Larsh SE, Gurney CW. Iron therapy in chronically fatigued, nonanemic women; a double-blind study. Ann Intern Med 1960; 52: 378-394.
  9. Blake DR et al. The importance of iron in rheumatoid disease. Lancet ii: 1142-4, 1981.
  10. Blake DR et al. Effect of intravenous iron dextran on rheumatoid synovitis. Ann Rheum Dis 44: 183-8, 1985.
  11. Buetler E, Larsh SE, Gurney CW. Iron therapy in chronically fatigued non-anemic women: A double blind study. Ann Intern Med 52: 378-94, 1960.
  12. Chua ACG, Morgan EH. Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat. Biol Trace Elem Res 1996; 55: 39-54.
  13. Cook J, Dassenko S, Whittaker P. Calcium supplementation. Effect on iron absorption. Am J Clin Nutr 1991; 53: 106-111.
  14. Dallman PR, Beutler E, Finch CA. Effects of Iron deficiency exclusive of anaemia Br J Haematol 1978; 40: 179-184.
  15. Dallman, PR. Iron. In: Present knowledge in nutrition. 6th edn. Washington DC: Nutrition Foundation. 1990: p 241-250.
  16. Dalton MA et al. Calcium and phosphorous supplementation of iron-fortified infant formula. No effect on iron status of healthy full-term infants. Am J Clin Nutr 1997; 65: 921-926.
  17. Edgerton VR, Ohira Y et al. Toleration of hemoglobin and work tolerance in iron deficient subjects. J Nutr Sci Vitaminol 1981; 27: 77-86.
  18. Fairweather Tait SJ, Minihane AM, Eagles J et al. Rare earth elements as nonabsorable fecal markers in studies of iron absorption. Am J Clin Nutr 1997; 65: 970-976.
  19. Dabbagh AJ. Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis 52:67-73, 1993.
  20. Dabbagh AJ. Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis 52:67-73, 1993.
  21. Davidson A et al. Red cell ferritin content: A re-evaluation of indices for iron deficiency in the anaemia of rheumatoid arthritis. Br Med J 289: 648-50, 1984.
  22. Gardner GW et al. Physical work capacity and metabolic stress in subjects with iron deficiency anemia. Am J Clin Nutr 30; 6: 910-17, 1977.
  23. Gleerup A, Rossander-Hulthen L, Gramatkovski E et al. Iron absorption from the whole diet: comparison of the effect of two different distributions of daily calcium intake. Am J Clin Nutr 1995; 61: 97-104.
  24. Green R, Charlton R et al. Body iron excretion in man; a collaborative study. Am J Med 1968; 45: 336-353.
  25. Hallber L. Bioavailability of dietary iron in man. Ann Rev Nutr 1981; 1: 123-147.
  26. Hallberg L, Nilsson L. Constancy of individual menstrual blood loss. Acta Obstet Gynecol Scand 1964; 43: 352-359.
  27. Hallberg L, Rossander L, Persson H. Deleterious effects of prolonged warming of meals on ascorbic acid content and iron absorption. Am J Clin Nutr 1982; 36: 846-850.
  28. Hallberg L, Brune M, Erlandsson M et al. Calcium. Effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr 1991; 53: 112-119.
  29. Hansen TM et al. Serum ferritin and the assessment of iron deficiency in rheumatoid arthritis. Scand J Rheumatol 12; 4: 353-9, 1983.
  30. Hansen TM, Hansen NE. Serum ferritin as indicator of iron responsive anemia in patients with rheumatoid arthritis. Ann Rheum Dis 45: 569, 1986.
  31. Hunt, JR, Gallagher, SK, Johnson, LK. Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 1994; 59: 1381-1385.
  32. Kent S, Weinberg E. Hypoferremia. Adaptation to disease? New Eng J Med 1989; 320: 672.
  33. Kies C, ed. Nutritional bioavailability of iron. Washington, DC: American Chemical Society. 1982.
  34. Kies, C, Bylund, DM. Iron status of adolescent boys and girls as influenced by variations in dietary ascorbic acid and iron intakes. Nutr Rep Intl 1989; 40: 43-51.
  35. Li R, Chen X, Yan H, et al. Functional consequences of Iron Supplementation in iron-deficient female cotton mill workers in Beijing, China. Am J Clin Nutr 59: 908-13, 1994.
  36. Lynch, SR. Interaction of iron with other nutrients. Nutr Rev 1997; 55: 102-110.
  37. Magnusson B, Bjorn-Rasmussen E, Hallberg L et al. Iron absorption in relation to iron status. Model proposed to express results of food iron absorption measurements. Scand J Haematol 1981; 27: 201-208.
  38. McCord, JM. Effects of positive iron status at a cellular level. Nutr Rev 1996; 54: 85-88.
  39. Muirden KD, Senator GB. Iron in the synovial membrane in rheumatoid arthritis and other joint diseases. Ann Rheum Dis 27: 38-48, 1968.
  40. Ohira Y, Edgerton VR, Gardner GW et al. Work capacity after iron treatment as a function of hemoglobin and iron deficiency. J Nutr Sci Vitaminol 1981; 27: 87-96.
  41. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 1983; 71: 877-880.
  42. Oski FA, Honig AS. The effects of therapy on the developmental scores of iron deficient infants. J Pediatr 1978; 92: 21-25.
  43. Pollitt E, Leibel RL. Iron deficiency and behavior. J Pediatr 1976; 88: 372-381.
  44. Pollitt E, Leibel RL, Greenfield DB. Iron deficiency and cognitive test performance in preschool children. Nutr Behavior 1983; 1: 137-146.
  45. Pollitt E, Soemantri AG, Yunis F, Scrimshaw NS. Cognitive effects of iron-deficiency anaemia. Lancet 1985; 1: 158.
  46. Prasad MK, Pratt CA. The effects of exercise and two levels of dietary iron on iron status. Nutr Res 1990; 10: 1273-1283.
  47. Rothwell RS, Davis P. Relationship between serum ferritin, anemia, and disease activity in acute and chronic rheumatoid arthritis. Rheumatol Int 1; (2): 65-7, 1981.
  48. Scrimshaw NS. Functional consequences of iron deficiency in human populations. J Nutr Sci Vitaminol 1984; 30: 47-63.
  49. Sempos, CT, Looker, AC, Gillum, RF. Iron and heart disease. The epidemiologic data. Nutr Rev 1996; 54: 73-88.
  50. Sheard, NF. Iron deficiency and infant development. Nutr Rev 1994; 52: 137-140.
  51. Stãhlberg MR, Savilahti E, Siimes MA. Iron deficiency in coeliac disease is mild and it is detected and corrected by gluten-free diet. Acta Paediatr Scand 80; (2):190-3, 1991.
  52. Tucker DM, Sandstead HH, Penland JG et al. Iron status and brain function: serum ferritin levels associated with asymmetries of cortical electrophysiology and cognitive performance. Am J Clin Nutr 1984; 39: 105-113.
  53. Voorhees ML, Stuart MJ et al. Iron deficiency anemia and increased urinary norepinephrine. J Pediatr 1g74; 86: 542-547.
  54. Vreugdenhil G et al. Efficacy and safety of oral iron chelator L1 in anaemic rheumatoid arthritis patients. Letter. Lancet ii: 1398-9, 1989.
  55. Walter T, Olivares M, Pizarro F et al. Iron, anemia, and infection. Nutr Rev 1997; 55: 111-124.
  56. Webb TE, Oski FA. Iron deficiency anemia and scholastic achievement in young adolescents. J Pediatr 1973; 82: 827-830.
  57. Webb TE, Oski FA. Behavioral status of young adolescents with iron deficiency anemia. J Spec Educ 1974; 8: 153-156.
  58. Willis WT et al. Iron deficiency: Improved exercise performance within 15 hours of iron treatment in rats. J Nutr 120; 8: 909-16, 1990.
  59. Yip, R, Dallman, PR. Iron. In: Present knowledge in nutrition. 7th edn. Washington, DC: Nutrition Foundation. 1996: p 277-292.
  60. Zittoun J, Blot 1, Hill C et al. Iron supplements versus placebo in pregnancy. Its effects on iron and folate status on mothers and newborns. Ann Nutr Metabol 1983; 27: 320-327.

Sources:
Joseph E. Pizzorno Jr., Michael T. Murrey & Melvyn R. Werbach.