vitamin and mineral interactions: the complex relationship of essential nutrients

 

Deanna Minich, PhD, CNS, IFMCP explains how essential nutrients can both help or hinder each other and our health. Reprinted with permission. Originally posted on Jan 2, 2018 at deannaminich.com.  See her bio below.

The essential vitamins and minerals share a delicate dance in the body. For many body processes to function optimally, you must have the right balance of the nutrients. Many nutrients work synergistically, so a deficiency in one might appear as or exacerbate a deficiency in another and vice versa.
Other nutrients are antagonists, so care must be taken when supplementing with one so it does not negatively impact the absorption, uptake, or metabolism of the other. For some nutrient pairs, the balance is delicate, with the pairs in certain situations enhancing the work of the other, and in other situations, they antagonize one another.
The following is a brief overview of the relationships and interactions between the essential nutrients. As you will see, some vitamins and minerals have a relationship with several other essential nutrients, while some have few if any known synergistic or antagonistic interactions.

VITAMINS

​Vitamin A

​Synergistic Nutrients:
Vitamin E

• Vitamin E enhances vitamin A intestinal absorption at medium to high concentrations, up to 40 percent.
• Vitamin A and E together lead to increased antioxidant capabilities, protect against some forms of cancer, and support a healthier gut.
• They work synergistically to prevent or support obesity, metabolic syndrome, inflammation, immune response, brain health, hearing loss.

Iodine

• Retinoic acid is involved in iodine uptake.
• Severe vitamin A deficiency decreases the uptake of iodine and impacts thyroid metabolism.
• Iodine deficiency and vitamin A deficiency leads to a more severe case of primary hypothyroidism compared to iodine deficiency alone.

Iron

• Iron is required for converting beta-carotene into retinol.
• Vitamin A increases iron absorption, especially non-heme iron.
• Iron increases the bioavailability of pro-vitamin A carotenoids, including alpha-carotene, beta-carotene, and beta-cryptoxanthin.
• Supplementing with vitamin A might help reverse iron deficiency anemia in children, and vitamin A deficiency might contribute to anemia.

Zinc

• Zinc is required for vitamin A transport.
• Supplementing with vitamin A and zinc in children led to a reduced risk of infection and increased linear growth.
• Zinc along with vitamin A helps maintain eye health.

 
Antagonistic Nutrients:
Vitamin E

• High levels of beta carotene might decrease serum levels of vitamin E.

Vitamin K

• Vitamin A toxicity inhibits the synthesis of vitamin K2 by intestinal bacteria and interferes with hepatic actions of vitamin K.
• Vitamin A interferes with absorption of vitamin K.

Vitamin B1 (Thiamin)

Synergistic Nutrients
 Magnesium

• Magnesium is required to convert thiamin to its biologically active form and is also required for certain thiamin-dependent enzymes.
• Overcoming thiamin deficiency might not occur if magnesium deficiency is not co-treated.

Antagonistic Nutrients
Vitamin B6

• Vitamin B6 can inhibit the biosynthesis of thiamin.

Vitamin B2 (Riboflavin)

Antagonistic Nutrients:
Calcium

• Calcium might form a chelate with riboflavin, decreasing riboflavin absorption.

Vitamin B3 (Niacin)

Synergistic Nutrients:
Zinc

• Supplementing with nicotinic acid might provide a dose-dependent improvement in hepatic zinc levels and better antioxidant markers, including less lipid peroxidation, reduced glutathione levels.

Vitamin B5 (Pantothenic Acid)

Antagonistic Nutrients:
Copper

• Copper deficiency increases vitamin B5 requirements.

Vitamin B6 (Pyridoxine)

Synergistic Nutrients:
 Magnesium

• Magnesium enhances the uptake of vitamin B6 and vice versa.
• Co-supplementing with vitamin B6 and magnesium helps PMS symptoms and possibly autism.

 
Antagonistic Nutrients:
 Vitamin B1

• Vitamin B6 can inhibit the biosynthesis of thiamin.

Vitamin B9

• Vitamin B6 increases folate requirements and possibly vice versa.
• Along with vitamin B12, co-supplementation with vitamins B9 and B6 improves homocysteine levels, of which high levels have been linked to cardiovascular disease, thrombin generation, and neurodegeneration.

Zinc

• High levels of vitamin B6 might increase the need for zinc.
• Chronic and acute vitamin B6 deficiency increases intestinal uptake of zinc but serum zinc levels decrease, demonstrating an impairment in zinc utilization.

 
Vitamin B9 (Folate)

Antagonistic Nutrients
Vitamin B6

• Vitamin B6 increases folate requirements and possibly vice versa.

Vitamin B12

• Supplementing with B9 increases the need for B12 and vice versa because both play key roles in the methylation cycle.
• Deficiency or insufficiency can increase homocysteine levels, which are connected to a higher risk of dementia, Alzheimer’s disease, and cardiovascular disease.
• Deficiency can also cause megaloblastic anemia.

Zinc

• Supplementation with folic acid, especially in a state of zinc deficiency, might reduce absorption of zinc through forming a chelate, but there are mixed results.

Vitamin B12 (Cobalamin)

Antagonistic Nutrients
Vitamin C

• In aqueous solution, vitamin C might degrade B12 especially when B1 and copper are also present.

Vitamin B9

• Supplementing with B9 increases the need for B12 and vice versa because both play key roles in the methylation cycle.
• Deficiency or insufficiency can increase homocysteine levels, which are connected to a higher risk of dementia, Alzheimer’s disease, and cardiovascular disease.
• Deficiency can also cause megaloblastic anemia.

 
Vitamin C (Ascorbic Acid)

Synergistic Nutrients
Vitamin E

• Vitamins C and E work synergistically for antioxidant defense, with vitamin C regenerating vitamin E.
• Works in synergy, so large supplementation of one needs large supplement of other.

Copper

• Post-absorptive, vitamin C can stimulate uptake and metabolism of copper.
• Vitamin C deficiency could lead to symptoms of copper deficiency.

Iron

• Increases absorption of non-heme iron, even in the presence of inhibitory substances; vitamin C also regulates uptake and metabolism of iron.

Selenium

• A diet high in vitamin C led to increased percent of absorption of sodium selenite and retention of the absorbed selenium.

Antagonistic Nutrients
Vitamin B12

• In aqueous solution, vitamin C might degrade B12, especially with B1 and copper also present.

Copper

• High levels of vitamin C inhibits absorption of copper, possibly through increasing iron absorption, which is a copper antagonist.

Iron

• Excess vitamin C could increase iron overload risk.

Selenium

• Converts sodium selenite to elemental selenium which inhibits absorption but only when supplements are taken on an empty stomach.

Vitamin D

Synergistic Nutrients
Vitamin K

• Optimal levels of vitamin K prevents some of the problems of excess vitamin D and leads to better outcomes.
• Sufficient levels of vitamins D and K lead to reduced risk of hip fractures and an increase in BMD and other markers of bone health.
• Sufficient vitamin K and D also improves insulin levels and blood pressure while reducing the risk of arthrosclerosis.

Calcium

• Vitamin D increases calcium absorption.
• Along with vitamin K, supplementing with calcium and vitamin D leads to improved bone, heart, and metabolic health.
• Calcium and vitamin D also work synergistically for skeletal muscle function.
• Co-supplementation of vitamin D and calcium led to an improved response to children with rickets.

Magnesium

• Supplementing with vitamin D improves serum levels of magnesium especially in obese individuals.
• Magnesium is a cofactor for the biosynthesis, transport, and activation of vitamin D.
• Supplementing with magnesium improves vitamin D levels.
• Deficiency in both vitamin D and magnesium increase risk for cardiovascular disease, diabetes, metabolic disease, and skeletal disorders.

Selenium

• Supplementing with vitamin D improves serum levels of selenium.

Antagonistic Nutrients
Vitamin A

• High levels of vitamin A decrease vitamin D uptake by 30 percent.

Vitamin E

• Medium and high levels of vitamin E significantly reduce vitamin D uptake by 15 percent and 17 percent respectively.

Vitamin E

Synergistic Nutrients
Vitamin A

• Vitamin E enhances vitamin A intestinal absorption at medium to high concentrations, up to 40 percent.
• Vitamin A and E together lead to increased antioxidant capabilities, protect against some forms of cancer, and support a healthier gut.
• They work synergistically to prevent or support obesity, metabolic syndrome, inflammation, immune response, brain health, hearing loss.

Vitamin C

• Vitamins C and E work synergistically as antioxidant defense, with vitamin C regenerating vitamin E.
• Because they work synergistically, large supplementation of one needs large supplementation of other.

Selenium

• Selenium deficiency aggravates effects of deficiency of vitamin E and vitamin E can prevent selenium toxicity.
• Together they induce apoptosis.
• Combined selenium and vitamin E deficiency has a great impact that the deficiency of one of the nutrients.
• Synergy of vitamin E and selenium might help with cancer prevention through stimulating apoptosis in abnormal cells; selenium and vitamin E work synergistically to help mitigate iron excess.

Zinc

• Some effects of zinc deficiency were helped by vitamin E supplementation.

Antagonistic Nutrients
Vitamin A

• Vitamin A reduces vitamin E intestinal uptake in a dose-dependent manner.
• High levels of beta carotene might decrease serum levels of vitamin E.

Vitamin D

• Vitamin D reduces vitamin E intestinal uptake in a dose-dependent manner.

Vitamin K

• Metabolites can inhibit vitamin K activity, so care is needed when supplementing with high doses.
• Also, large doses of vitamin K inhibit intestinal absorption of vitamin E.

Iron

• Iron interferes with absorption of vitamin E.
• Vitamin E deficiency exacerbates iron excess but supplemental vitamin E prevented it.
• It is best to take the supplements at separate times.

Vitamin K

Synergistic Nutrients:
 Vitamin D

• Optimal levels of vitamin K prevents some of the problems of excess vitamin D and leads to better outcomes.
• Sufficient levels of vitamins D and K lead to reduced risk of hip fractures and an increase in BMD and other markers of bone health.
• It also improves insulin levels, blood pressure, and reduces the risk of arthrosclerosis.

Calcium

• Along with vitamin D, vitamin K and calcium help to improve bone and heart health.

 Antagonistic Nutrients
 Vitamin A

• Vitamin A toxicity inhibits synthesis of vitamin K2 by intestinal bacteria and interferes with hepatic actions of vitamin K.
• Vitamin A inhibits intestinal absorption of vitamin K.

Vitamin D

• Inhibits intestinal absorption of vitamin K.

Vitamin E

• Metabolites can inhibit vitamin K activity, so care is needed when taking large doses.
• Vitamin E can also inhibit the intestinal absorption of vitamin K.

MACROMINERALS  
Calcium

Synergistic Nutrients
Vitamin D

• Vitamin D increases calcium absorption.
• Along with vitamin K, supplementing with calcium and vitamin D leads to improved bone, heart, and metabolic health.
• Calcium and vitamin D also work synergistically for skeletal muscle function.
• Co-supplementation of vitamin D and calcium led to an improved response to children with rickets.

Potassium

• Potassium enhances calcium reabsorption.
• Potassium excretion is positively related to bone mineral density.

​Antagonistic Nutrients
Iron

• High levels of calcium decrease absorption of non-heme iron in the short term but might not have a long-term impact on iron levels; this can be mitigated by vitamin C.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

Magnesium

• High levels of calcium decreased tissue levels of magnesium and exacerbates deficiency and decreases magnesium absorption.
• Magnesium supplementation can decrease calcium absorption, especially in those with renal stone disease.

Manganese

• Manganese and calcium compete for absorption and display similar properties.

Phosphorus

• High levels of calcium supplements decrease phosphorus absorption.
• The ideal ratio of phosphorus to calcium is 1:1. Higher levels of phosphorus to calcium ratio was shown to hurt bone health in pigs and humans.

Sodium

• Excess sodium enhances calcium excretion.
• High sodium increases bone turnover and reduces BMD.

Zinc

• High levels of calcium supplements decrease zinc absorption and zinc balance.
• High levels of zinc might impact calcium absorption.
• Zinc deficiency reduces serum calcium levels and calcium entry into cells, and it increases PTH levels.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

Magnesium

Synergistic Nutrients
Vitamin B1

• Magnesium is required to convert thiamin to its biologically active form and is also required for certain thiamin-dependent enzymes.
• Overcoming thiamin deficiency might not occur if magnesium deficiency is not co-treated.

Vitamin B6

• Magnesium enhances the uptake of vitamin B6 and vice versa.
• Co-supplementing with vitamin B6 and magnesium helps PMS symptoms and possibly autism.

Vitamin D

• Supplementing with vitamin D improves serum levels of magnesium especially in obese individuals.
• Magnesium is a cofactor for the biosynthesis, transport, and activation of vitamin D.
• Supplementing with magnesium improves vitamin D levels.
• Deficiency in both vitamin D and magnesium increase risk for cardiovascular disease, diabetes, metabolic disease, and skeletal disorders.

Potassium

• Magnesium is required for potassium uptake in cells.
• Combination of magnesium, calcium, and potassium reduces the risk of stroke.

Antagonistic Nutrients
Calcium

• High levels of calcium decreased tissue levels of magnesium and exacerbates deficiency and decreases magnesium absorption.
• Magnesium supplementation can decrease calcium absorption, especially in those with renal stone disease.

Zinc

• Supplements of high levels (142 mg/day) of zinc might reduce magnesium absorption.

Phosphorus

• Along with calcium, phosphorus can reduce the absorption of magnesium in the intestines.

Phosphorus

Antagonistic Nutrients
Calcium

• High levels of calcium supplements decrease phosphorus absorption.
• The ideal ratio of phosphorus to calcium is 1:1; higher levels of the phosphorus to calcium ratio was shown to hurt bone health in pigs and humans.

Magnesium

• Along with calcium, phosphorus can reduce the absorption of magnesium in the intestines.

Potassium

Synergistic Nutrients
Calcium

• Potassium enhances calcium reabsorption.
• Potassium excretion is positively related to bone mineral density.

Magnesium

• Magnesium is required for potassium uptake in cells.
• Combination of magnesium, calcium, and potassium reduces the risk of stroke.

Sodium

• Potassium/Sodium balance required for optimal health, especially for reduced blood pressure and heart health.
• The right potassium to sodium balance increases bone health through decreasing excess excretion of calcium due to high levels of sodium.
• It also decreases obesity load and improves net dietary acid load.

Sodium

Synergistic Nutrients
 Potassium

• Potassium/Sodium balance required for optimal health, especially for reduced blood pressure and heart health.
• The right potassium to sodium balance increases bone health through decreasing excess excretion of calcium due to high levels of sodium.
• It also decreases obesity load and improves net dietary acid load.

 
Antagonistic Nutrients
 Calcium

• Excess sodium enhances calcium excretion.
• High sodium increases bone turnover and reduces bone mineral density.

TRACE MINERALS
Copper

Synergistic Nutrients
 Vitamin C

• Post-absorptive, vitamin C can stimulate uptake and metabolism of copper.
• Vitamin C deficiency could lead to symptoms of copper deficiency.

 Antagonistic Nutrients
 Vitamin C

• High levels of vitamin C inhibits absorption of copper, possibly through increasing iron absorption, which is a copper antagonist.

Iron

• Copper and iron compete for absorption, so high levels of one might lead to deficiency of the other.

Molybdenum

• Molybdenum interacts with protein-bound copper in and outside the cells and can even remove copper from the tissues, so excess molybdenum contributes to copper deficiency.
• Molybdenum can also be used to treat problems associated with excess levels of copper, such as Wilson’s disease.
• The antagonistic relationship between copper and molybdenum might contribute to diabetic complications.

Selenium

• When consuming low to normal levels of selenium, high intakes of copper reduces absorption, although this might not occur when consuming high levels of selenium.
• An imbalance of selenium and copper ratio could contribute to oxidative stress.

Zinc

• Zinc inhibits copper absorption and can lead to a deficiency.
• A high copper to zinc ratio increases oxidative stress, all-cause mortality, inflammation, immune dysfunction, sleep disturbances, AD, heart failure, physical disability, diabetes, and autism.

Iodine

Synergistic Nutrients
 Vitamin A

• Retinoic acid is involved in iodine uptake.
• Severe vitamin A deficiency decreases the uptake of iodine and impacts thyroid metabolism.
• Iodine deficiency and vitamin A deficiency leads to a more severe case of primary hypothyroidism compared to iodine deficiency alone.

Selenium

• Adequate levels of both iodine and selenium are necessary for the metabolism of thyroid hormone. Selenium is required for the enzyme that deiodinizes T3 to convert it to the active form, T4.
• Concurrent iodine and selenium deficiencies might create a balancing effect to maintain and normalize T4 levels while T4 levels were lowered when there was a deficiency of iodine or selenium.

Iron

Synergistic Nutrients
Vitamin A

• Iron is required for converting beta carotene into retinol.
• Vitamin A increases iron absorption, especially non-heme iron.
• Iron increases the bioavailability of pro-vitamin A carotenoids, including alpha-carotene, beta-carotene, and beta-cryptoxanthin.
• Supplementing with vitamin A might help reverse iron deficiency anemia in children but vitamin A deficiency might contribute to anemia.

Vitamin C

• Vitamin C increases absorption of non-heme iron, even in the presence of inhibitory substances; vitamin C also regulates uptake and metabolism of iron.

Antagonistic Nutrients
Vitamin E

• Iron interferes with absorption of vitamin E.
• Vitamin E deficiency exacerbates iron excess but supplemental vitamin E prevented it.
• It is best to take the supplements at separate times.

Calcium

• High levels of calcium decrease absorption of non-heme iron in the short term but might not have a long-term impact on iron levels; this can be mitigated by vitamin C.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

Copper

• Copper and iron compete for absorption, so high levels of one might lead to deficiency of the other.

Manganese

• High levels of manganese inhibits iron absorption and uptake in a dose-dependent manner and vice versa due to shared pathways of absorption and similar physiochemical properties.

Zinc

• Non-heme iron and zinc compete for absorption.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

 
Manganese

Antagonistic Nutrients
Iron

• High levels of manganese inhibits iron absorption and uptake in a dose-dependent manner and vice versa due to shared pathways of absorption and similar physiochemical properties.

Calcium

• Manganese and calcium compete for absorption and display similar properties.

 
Molybdenum

Antagonistic Nutrients
Copper

• Molybdenum interacts with protein-bound copper in and outside the cells and can even remove copper from the tissues, so excess molybdenum contributes to copper deficiency.
• Molybdenum can also be used to treat problems associated with excess levels of copper, such as Wilson’s disease.
• The antagonistic relationship between copper and molybdenum might contribute to diabetic complications.

 
Selenium

Synergistic Nutrients
Vitamin C

• A diet high in vitamin C led to increased percent of absorption of sodium selenite and retention of the absorbed selenium.

Vitamin D

• Supplementing with vitamin D improves serum levels of selenium.

Vitamin E

• Selenium deficiency aggravates effects of deficiency of vitamin E and vitamin E can prevent selenium toxicity.
• Together they induce apoptosis.
• Combined selenium and vitamin E deficiency has a great impact that the deficiency of one of the nutrients.
• Synergy of vitamin E and selenium might help with cancer prevention through stimulating apoptosis in abnormal cells; selenium and vitamin E work synergistically to help mitigate iron excess.

Iodine

• Adequate levels of both iodine and selenium are necessary for the metabolism of thyroid hormone. Selenium is required for the enzyme that deiodinizes T3 to convert it to the active form, T4.
• Concurrent iodine and selenium deficiencies might create a balancing effect to maintain and normalize T4 levels while T4 levels were lowered when there was a deficiency of iodine or selenium.

Antagonistic Nutrients
Vitamin C

• Vitamin C converts sodium selenite to elemental selenium which inhibits absorption but only when supplements are taken on an empty stomach.

Copper

• When consuming low to normal levels of selenium, high intakes of copper reduces absorption, although this might not occur when consuming high levels of selenium.
• An imbalance of selenium and copper ratio could contribute to oxidative stress.

 
Zinc

Synergistic Nutrients
Vitamin A

• Zinc is required for vitamin A transport.
• In one study, supplementing with vitamin A and zinc in children led to a reduced risk of infection and increased linear growth.
• Zinc along with vitamin A helps maintain eye health.

Vitamin B3

• Supplementing with nicotinic acid might provide a dose-dependent improvement in hepatic zinc levels and better antioxidant markers, including less lipid peroxidation, reduced glutathione levels.

 Antagonistic Nutrients
 Vitamin B6

• High levels of B6 might increase the need for zinc.
• Chronic and acute B6 deficiency increases intestinal uptake of zinc but serum zinc levels decrease, demonstrating an impairment in zinc utilization.

Vitamin B9

• Supplementation with folic acid, especially in a state of zinc deficiency, might reduce absorption of zinc through forming a chelate, but there are mixed results.

Calcium

• High levels of calcium supplements decrease zinc absorption and zinc balance.
• High levels of zinc might impact calcium absorption.
• Zinc deficiency reduces serum calcium levels and calcium entry into cells, and it increases parathyroid hormone levels.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

Copper

• Copper inhibits zinc absorption and can lead to a deficiency.
• A high copper to zinc ratio increases risk of oxidative stress, all-cause mortality, inflammation, immune dysfunction, sleep disturbances, AD, heart failure, physical disability, diabetes, and autism.

Iron

• Non-heme iron and zinc compete for absorption.
• Supplementing with calcium and iron greatly reduced serum levels of zinc.

Magnesium

• Supplements of high levels (i.e. 142 mg/day) of zinc might reduce magnesium absorption.

As you can see, many of the minerals compete with one another for absorption, making it important to ensure proper balance so that one does not overpower the others, contributing to a deficiency.

​SPECIAL GROUP INTERACTIONS
Antioxidant Network

Zinc, selenium, vitamin A, vitamin C, vitamin E

• Balanced and sufficient quantities keep antioxidant enzymes and other antioxidant defenses high to mitigate oxidative stress, which is connected to numerous diseases, including Alzheimer’s disease, cardiovascular disease, obesity, cancer, and metabolic syndrome.
• Along with magnesium, antioxidant vitamins can also help to protect against hearing loss and reduce inflammation.

 
B-vitamins

 The B-vitamins often work together, especially vitamins B2, B6, B9, B12.

• In addition to the above one-on-one interactions, the B vitamins work together and play key role as cofactors and enzymes in one-carbon metabolism, which is involved in amino acid metabolism, nucleotide metabolism, and DNA methylation, as well as production of SAM, which is a methyl donor used in various reactions including neurotransmitter production. These cofactors and enzymes are also involved in energy metabolism.
• A balance of B vitamins supports brain health, including neural development and prevention of neurodegenerative diseases, as well as cardiovascular health.

As always, check with your healthcare practitioner to see which vitamins and minerals you may need and how best to take them.

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Dr. Deanna Minich is an internationally-recognized teacher, author, scientist, speaker, and artist.  She has more than 20 years of diverse, well-rounded experience in the fields of nutrition and functional medicine, including clinical practice, research, product formulation, writing, and education. Her doctoral (Ph.D.) research focused on essential fatty acid absorption and metabolism, and her Master of Science degree (M.S.) allowed her to explore the health benefits of the colorful, plant-based carotenoids. She has authored six books on health and wellness and over fifteen scientific publications. Currently, she is Faculty for the Institute for Functional Medicine and the University of Western States. She has developed an online certification program for health professionals so that they can apply the color-coded 7 Systems of Full-Spectrum Health in their practice. Her lectures are heard by patients and practitioners throughout the world. Dr. Minich’s passion is teaching a whole-self approach to nourishment and bridging the gaps between science, spirituality, and art in medicine.
You can learn more and connect with Dr. Minich here:
Websites:
Deanna Minich Events, Blog & Info: www.deannaminich.com
Certification Program: www.foodandspirit.com
Whole Detox: www.whole-detox.com
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