There are many interactions between nutrients which can affect their absorption and impact on your health. Many manufacturers and consumers do not realize that improper mixtures of ingredients can have serious hazards. For instance, calcium supplements may lead to zinc deficiency as calcium can block absorption of zinc. Does the form of a nutrient matter, such as chelated minerals, or a particular form of calcium or vitamin C? What about time release pills?

Nutrient Interactions, edited by C.E. Bodwell and J. W. Erdman, Jr., (Marcel Dekker, Inc., New York, 1988) is an excellent book reviewing scientific studies of interactions between vitamins and minerals, of which most people, including professionals, are unaware. However, it should be noted that only a few of the numerous studies are cited below! The purpose here is to demonstrate that it is important to carefully consider any supplement formulation. Anyone can mix nutrients and sell you a pill, and you can buy a variety of vitamins and minerals in the store and take them - but getting the scientifically justified combination is much more challenging.

See the appropriate numbered statement below for references and details. For interactions related to specific medications, please click here.

1. Calcium supplements interfere with absorption of zinc.

2. High levels of phosphate in the U.S. diet interfere with calcium metabolism and contribute to osteoporosis.

3. Vitamins C and E act synergistically with other antioxidants like selenium, beta- carotene, zinc, and copper. It is likely that taking high dosages of these two antioxidants will spare the need for any intake above the Daily Values which should be obtained from a healthy diet.

4. High doses of zinc (on the order of 50 mg/day) can interfere with the absorption of a variety of other important minerals.

5. Other interactions are possible when nutrients are taken in concentrated supplement dosages, which is why it is desirable to obtain the Daily Values for nutrients through a well- balanced diet.

6. The form of a micronutrient usually does not have a significant effect on absorption.

7. Medications can affect your requirement for vitamins and minerals.

1. Calcium supplements interfere with absorption of zinc.

Wood, R.J., and Zheng, J.J., "High dietary calcium intakes reduce zinc absorption and balance in humans", Am J Clin Nutr. 65: 1803-9 (1997)

quantitative report confirming that anyone taking calcium supplements should take an appropriate amount of zinc at the same time or risk zinc deficiency - I believe ours is the only product which has this proper formulation and ratio of zinc and calicum! "Our findings suggest that high-calcium diets [or supplements] can reduce net zinc absorption and balance and may increase the zinc requirement in adult humans." "Zinc deficiency has many untoward effects, including loss of appetite, growth retardation, skin changes, and immunologic abnormalities."

Harvard Women's Health Watch 5 (Jan, 98), In "Zooming in on zinc", pg 6

"researchers found that in women and men who took a 600-mg calcium pill with a meal containing about 7 mg of zinc, zinc absorption was reduced by 50%. However, adding about 8 mg of zinc to the calcium supplement offset the decline." "Zinc supplements of 50 mg per day can cause a decrease in the important enzyme superoxide dismutase..Excessive intakes of zinc have also caused low levels of high-density lipoproteins, increasing the effects of low-density lipoproteins that in theory contribute to atherosclerosis and heart disease." The RDA is 12 mg, but most women get less than 10, with elderly getting about 9.

2. High levels of phosphate in the U.S. diet interfere with calcium metabolism and contribute to osteoporosis.

PHOSPHORUS/CALCIUM - Phosphorus intake can interfere with calcium absorption, and cause elevated calcium excretion and bone mineral loss. This is of particular concern for those who consume high quantities of soft drinks, many of which contain high levels of phosphate.

Winick, M., Nutrition in Health and Disease, John Wiley & Sons, New York, 1980, pg. 179

"There is no question that the kind of calcium:phosphorus ratio consumed by many people will promote bone resorption in ...humans." [people generally should get more calcium and less phosphorus - soda is high in phosphorus]

3. Vitamins C and E act synergistically with other antioxidants like selenium, beta-carotene, zinc, and copper. It is likely that taking high dosages of these two antioxidants will spare the need for any intake above the Daily Values which should be obtained from a healthy diet.

The vitamin C/Vitamin E/Vitamin A/Beta-carotene interaction is particularly important for those concerned about anitoxidants and age-associated disease. Major antioxidant micronutrients include vitamin C, vitamin E, beta-carotene, zinc, and selenium. As all are involved in certain ways in trapping free radicals, it is useful to learn how these interact. High dosages of vitamin E and beta-carotene have been shown to have "pro-oxidant" activity, just the opposite of an antioxidant, while high dosages of zinc and selenium are also known to be hazardous. However, because these all appear to trap free radicals, the levels can be adjusted to optimize protection. Two very exciting studies below demonstrate that vitamins C and E, the safest antioxidants at high dosages, are also the two most likely to trap free radicals. Those with elevated levels of vitamins C and E appear to need much lower, safer levels of beta- carotene, selenium and zinc which can be readily obtained from a good diet.

Kohlmeier, L. and Hastings, S. B. , "Epidemiological Evidence Of A Role Of Carotenoids In Cardiovascular Disease Prevention", Am J Clin Nutr 62(suppl): 1370S-6S (1995)

"findings from the first single intervention trial conducted on a large free-living population casts doubt on the utility of beta-carotene for all high-risk populations." "In vitro studies have shown that first alpha-tocopherol, then gamma-tocopherol, and then lycopene are consumed before beta-carotene is utilized as an antioxidant in LDL", therefore, with an adequate supply of vitamin E, there is no need for b-carotene supplement which has risks associated with it.

Thomas, S.R., Neuzil, J., Mohr, D. and Stocker, R., "Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein", Am. J. Clin. Nutr. 62: 1357S-64S (1995)

"The oxidation of low-density lipoproteins (LDLs) is now commonly implicated as an important early event in atherogenesis. The resulting interest in LDL antioxidation has focused on alpha- tocopherol...We review...how the vitamin's antioxidant activity is enhanced or even dependent on the presence of suitable reducing species [especially vitamin C]". "alpha-tocopherol itself does not act as a chain-breaking antioxidant but rather facilitates the transfer of radical reactions from the aqueous phase into LDL" [Table 1 shows composition of LDL (molecules/LDL particle), including alpha-(6-12) and gamma-(0.5) tocopherol, ubiquinol-1(0.5-0.8), lycopene(0.2-0.7), and beta-carotene(0.1-0.4). All of these facilitate radical trapping, and any reduces free radical damage.]

4. High doses of zinc (on the order of 50 mg/day) can interfere with the absorption of a variety of other important minerals.

ZINC/COPPER - "feeding zinc levels out of proportion to copper has important biological consequences" (pg. 132). "Pharmacological doses of zinc can produce human copper deficiency" (pg 134). At a zinc dosage of 150 mg/day, copper deficiency anemia was described in patients with sickle cell disease. Interactions like this are the basis for concern with people taking 50 mg zinc/day common in many supplements.

COPPER WITH ZINC, MOLYBDENUM, VITAMIN C: zinc decreases absorption, molybdenum increases excretion, vitamin C has no effect:

Turnlund, JR, "Copper nutriture, bioavailability, and the influence of dietary factors", J Am Diet Assoc 88:303-8 (1988)

"The range for copper, 2 to 3 mg/day, is higher than the usual dietary copper intake of many individuals in this country. On the basis of balance studies, a requirement of 1.3 mg/day has been suggested...Copper deficiency symptoms have seldom been observed in human beings."

Ages 60-60 men women ESADDI

Intake 1.17 mg 0.86 mg 2-3 mg

Interactions: "Serum copper was not affected by the ascorbic acid level [up to 600 mg]." [but was affected by 1,500 mg/day] " "In the presence of excessive zinc, copper bioavailability is impaired...This has led to concern about the effect of zinc intake slightly above the RDA of 15 mg/day on copper status." "One balance study in human beings provided evidence that dietary molybdenum slightly above the RDA of 0.15 to 0.50 mg/day increased urinary copper significantly."

ZINC/IRON - Zinc and iron compete with each other for absorption, so that taking a zinc supplement may lower iron absorption, and vice-versa (pg 127-9). Five young men and five young women were supplemented for 14 days with 100 mg of iron daily. When then given 50 mg of zinc, they absorbed 50% less than prior to the iron treatment.

ZINC/FOLATE - Folate supplements are reported to exert a negative effect on zinc absorption. (Pg 178). In particular, one study showed that 150 mcg of folacin/day decreased zinc absorption at levels of 3.5 or 7.5 mg/day. It appears that folate intake must be balanced with supplemental zinc.

5. Other interactions are possible when nutrients are taken in concentrated supplement dosages, which is why it is desirable to obtain the Daily Values for nutrients through a well-balanced diet. For instance, on MEDLINE, no research could be found to indicate that the micronutrients in any multivitamin formulation are actually absorbed into one's body. Most products claim to dissolve in a glass of water, but we all know that our digestive tracts are not a glass of water.

CALCIUM/VITAMIN D- Combs, Jr., G.F. The Vitamins: Fundamental Aspects in Nutrition and Health, Academic Press, New York, 1992

pg 349 - Vitamin D - "the body can synthesize vitamin D with the help of sunlight...These discoveries suggest that vitamin D may have numerous functions, including regulation of the immune system...Whereas vitamin D deficiency depresses calcium absorption and produces low blood calcium and abnormal bone minerilization, an excess of the vitamin does the opposite." [Thus, Personal Health Corporation has only the trace required for mature women who are less likely to get sufficient sunlight.]

CALCIUM/MAGNESIUM - High dosages of calcium, especially in supplement form may interfere with the absorption of magnesium (pg. 125). For instance, there was a significant reduction in magnesium absorption when dietary calcium was increased from 800 to 2,400 mg/day in young, healthy volunteers.

VITAMIN INTERACTIONS: (taken from Table 12.1 pg 288)

One vitamin needed for optimum absorption of another

Vitamin B6/vitamin B12; Folate/Thiamin

One vitamin may interfere with the other

Vitamin E/vitamin K; vitamin B6/niacin; thiamin/riboflavin

One vitamin can protect against destruction of the other

Vitamin E/vitamin A

Vitamin C/Vitamin E

6. The form of a micronutrient usually does not have a significant effect on absorption.

A. According to the scientific and medical reports found in a survey of MEDLINE, calcium is absorbed approximately as readily whether it is in the form of calcium carbonate, calcium chloride, calcium phosphate, or any other form.

B. According to the scientific and medical reports found in a survey of MEDLINE, vitamin C is absorbed at about the same rate whether it is in the form of vitamin C or other forms. The makers of Ester-C in particular claim that it is absorbed better - but how much better? At a significantly higher cost, studies indicate that it is absorbed perhaps 5% better. At Walmart in April, 1998, the price of a 500 mg tablet of Ester-C was 8.27 cents vs. 1.79 cents for generic vitamin C. That's 5% better absorption for 460% more money - not a very worthwhile investment to my mind.

C. Chelated minerals and chelated trace minerals cost considerably more than simple trace minerals, and there is no evidence which could be found to indicate any advantage of these more expensive products except marketing claims by the vendor.

D. Natural versus synthetic vitamins - There is absolutlely no physical or chemical difference between a molecule of vitamin C purified from a natural source, or chemically synthesized from atoms of carbon, oxygen, and hydrogen. In fact, as I discovered when we began exploring labelling of vitamins, legally the term "natural" on vitamins is meaningless. For instance, the method to chemically synthesize vitamin C is to take sugar from corn, and chemically convert it into vitamin C. This is synthetic vitamin C. But it is also legal to label it natural vitamin C - it came from corn after all.

The one possible exception to this rule is vitamin E. Synthetic vitamin E is pure alpha-tocopherol, one of 4 isomers (variations in structure) of the vitamin E structure. Natural vitamin E occurs in alpha-, beta-, gamma-, and delta-tocopherol forms. Most natural vitamin E tablets consists of pure alpha-tocopherol. However, it is possible to get "mixed tocopherols", and this natural mixture of forms is likely to be better for you than pure natural or synthetic alpha-tocopherol. But in general, when you pay for an all natural nutritional supplement, you are probably paying for the word on the label, not for any difference in the product. Marketing experts know that consumers will pay more for the word "natural" on the label, whatever is inside.

7. Drug interactions

Bigaouette, J, Timchalk, MA, and Kremer, J., "Nutritional adequacy of diet and supplements in patients with rheumatoid arthritis who take medications", J Am Diet Assoc 87: 1687-9 (1987)

52 patients; "Dietary intake of folic acid, pyridoxine, zinc and magnesium was 60% to 80% of the RDA" "The medications taken by the patients have known interactions with nutrients. D-penicillamine chelates zinc, copper, cobalt, and magnesium and inactivates pyridoxine. Prednisone increases urinary excretion of zinc, calcium, and nitrogen. Methotrexate interferes with folic acid metabolism and was reported to reduce hepatic stores by more than 80%. Aminosalicylic acid and nonsteroidal anti-inflammatory medications decrease iron stores through gastronintestinal erosion and chronic blood loss."

LOTS MORE: Possible Hazards of Supplements including Vitamins

Found in a variety of sources
Use the find command on your computer to search items you consider taking. Note this is a list that includes speculation by various authors and many of these hazards may never have been observed clinically.
1. "Total Nutrition: The Only Guide You Will Ever Need", V. Herbert and G. J. Subak-Sharpe, St. Martin's Press, NY, 1995.
See pages 101-104.
2. August 1998, Berkeley Wellness Letter, Echinacea - "benefits unproven. Little known about toxicity. Prescribed in Germany for colds and flu. Little known about toxicity." It is speculated that Echinacea may cause allergies or immune hyperactivity.
3. Complete Guide to Vitamins, Minerals, and Supplements, H. Winter Griffith, MD, Fisher Books, AZ, 1988

B-vitamins

B1-
Precautions: Don't take if you are allergic
Adverse reactions: (rare) Skin rash or wheezing
B2-
Precautions: Don't take if you are allergic or have kidney failure
Adverse reactions:
B3-
Precautions: Don't take if you have allergy to vitamin B3, impaired liver function, active peptic ulcer, diabetes, gout, gallbladder disease
Adverse reactions: diarrhea, abdominal pain, faintness, headache, jaundice, nausea, skin dryness, vomiting
B5-
Precautions: Don't take if you are allergic or are taking levodopa for Parkinson's disease
Adverse reactions: none
B6-
Precautions: Don't take if you are allergic or are taking levodopa for Parkinson's disease
Adverse reactions: none

B9 -
Precautions: Don't take if you have pernicious anemia, or take anticonvulsant medicine
Adverse reactions: diarrhea, fever, skin rash

B12 -
Precautions: don't take if you are allergic to vitamin B12 or have Leber's disease.
Adverse reactions: Diarrhea (rare)

Vitamin C
Precautions: Don't take if you are allergic or have gout, kidney stones, or sickle cell anemia
Adverse reactions: anemia, flushed face, headache, increased urination, lower abdominal cramps, diarrhea, nausea, vomiting

Vitamin E
Precautions: Don't take if you are allergic to vitamin E, liver disease, cystic fibrosis, overactive thyroid, bleeding or clotting problems, iron-deficiency anemia
Adverse reactions: (all rare) Abdominal pain, breast enlargement, diarrhea, dizziness, flu-like symptoms, headache, nausea, fatigue, blurred vision.

Zinc-
Precautions: Don't take if you have ulcers
Adverse reactions: abdominal pain, abnormal bleeding, burning pain in upper chest relieved by food or antacid, mild diarrhea, nausea, vomiting

Alpha-lipoic acid -is a normal metabolic intermediate
" Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA, which is the same as lipoic acid), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. .... As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound." Jacob S; Henriksen EJ; Tritschler HJ; Augustin HJ; Dietze GJ, "Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid" [note thioctic acid is lipoic acid], Exp Clin Endocrinol Diabetes 1996;104(3):284-8
" To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability. (HRV). ..In a randomized, double-blind placebo-controlled multicenter trial ... patients ...were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months... Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). .. These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve ...patients" Ziegler D; Schatz H; Conrad F; Gries FA; Ulrich H; Reichel G, "Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie", Diabetes Care 1997 Mar;20(3):369-73
 
Conjugated linolenic acids - is found in large quantities in whole milk.
" One three-month preliminary study with 20 healthy volunteers showed that 3.6 grams of CLA a day decreased body fat from 21.3% to 17%. Atkinson described a longer study with more subjects which he is undertaking to determine if this reduction in fat is repeatable" INFORM, Vol 9 pg 69-72 (1998), "Scientific Forum Explores CLA Knowledge"

N-Acetyl-Carnitine - is a normal metabolic intermediate
" A rapidly growing body of evidence suggests that the apparent age-related deficits in mitochondrial functtion can be slowed or reversed by acetyl-L-carnitine (ALCAR), a normal component of the inner mitochondrial membrane...ALCAR has been shown to reverse the age- related decrease in [important mitochondrial functions]...Chronic administration of this compound to rats is associated with a reduction in the accumulation of lipofuscin...It has also been shown to attenuate the age-related decrements in active avoidance learning" Shigenaga, MK and Ames, BN, "Oxidants and mitochondrial decay in aging", pg 63-106, in Natural Oxidants in Human Health and Disease, B. Frei, ed., Academic Press, NY, 1994
" A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the
efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with
probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. ... Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints.... The study suggests that a subgroup of AD
patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly..." "A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease", Thal LJ; Carta A; Clarke WR; Ferris SH; Friedland RP; Petersen RC; Pettegrew JW; Pfeiffer E; Raskind MA; Sano M; Tuszynski MH; Woolson RF, Neurology 1996 Sep;47(3):705-11