TOP NUTRIENT-NUTRIENT INTERACTIONS TO KNOW FOR THE CNS EXAM WITH CAITLIN SELF

One of the most frequently asked questions about the CNS exam is which nutrient-nutrient interactions should be memorized. Learning micronutrient interactions for a standardized test can be extremely overwhelming - especially since there are so many! 

The bad news is that we don’t actually know which ones will be on the CNS test, but the good news is that this doesn’t seem to take up a huge portion of the exam either. 

This is one of those areas where there are a lot of individual facts, so test takers are tempted to memorize each of these individual facts for the CNS test. Memorization certainly has its place, but when it comes to micronutrients, I really recommend trying to put things in context rather than memorizing in isolation. 

→ Why do we often recommend Vitamin K2 when we take high doses of Vitamin D3? 

→ Why are B vitamins sometimes supplemented in a B complex rather than individually?

→ Why are calcium and magnesium often paired together in supplements?

We have a few different primary nutrient interactions. Some are beneficial and synergistic, while others are competitive and antagonistic. 

• Nutrient Synergy vs. Nutrient Antagonism 

• Many synergistic relationships contain nutrients that are often found together in food or share common absorption.

• Most antagonistic relationships are dose dependent. 

Nutrient(s)	Mechanism	Outcome
Vitamin K2 + Vitamin D3 (& Calcium) (Food: canned sardines, canned salmon)	D3 increases Ca absorption; K2 activates proteins that direct Ca to bone (puts Ca in the right place)	Synergistic: When taken together: Prevents arterial calcification; strengthens bones
B Vitamins: Folate + Vitamin B12 + Vitamin B6 (Food: liver, fatty fish, egg)	Act as cofactors in one-carbon metabolism and homocysteine remethylation	Synergistic: Supports DNA synthesis and reduces homocysteine - they all work together in methylation
B Vitamins: Choline + Folate + B12 (Food: eggs, beef or chicken liver, salmon, cod)	Overlapping roles in methyl group donation	Synergistic: Maintains methylation balance and neurological health / can step in and step up when each other are failing
B Vitamins: B12 and Folate (Food: eggs, beef or chicken liver, salmon, cod)	Supplementation of one without the other can mask the deficiency of the other. Hematologically, anemia improves, but the neurological and DNA issues will not improve if you supp B12 and the deficiency is B9 or you supp B9 and the deficiency is B12.	Synergistic: Take together to support both vitamins (regular hematology work doesn’t have a way to differentiate which is deficient)
Calcium & Magnesium	Compete for intestinal absorption when taken in very high doses; Calcium wins	Antagonistic: Imbalance in mineral status (e.g., excess calcium may lower magnesium status)

This table can be expanded - and in your clinical practice, it probably should be expanded to include additional facts and risks and products. However, for the sake of the exam, keeping this simple but relevant is usually a better tactic. 

You can look at the different mechanisms of interactions to try and understand how the interactions actually work. There are more categories than this, but this is enough to get started. 

• Synergistic

  • Nutrient Absorption Support

    • Ex: Vitamin C enhances absorption of non-heme Iron

  • Nutrient Cofactor / Support

    • Ex: Vitamin B6 helps "escort" magnesium across cell membranes into the cells - making it more bioavailable for use. 

• Antagonistic

  • Nutrient Competition 

    • Ex: Calcium and iron compete for the same absorption pathways - and calcium is stronger. Therefore co-supplementation results in poor iron absorption. (This includes taking iron with dairy products.) 

  • Increasing Excretion

    • High sodium intake increases excretion of potassium 

Top Nutrient-Nutrient Interactions to Focus On for the CNS Exam

For the most basic, bare bones version of what nutrient-nutrient interactions to study for the CNS exam, here’s my advice. Look at the following 5 categories and spend some time on each one, understanding how they interact and their general mechanisms. You may need to draw out a diagram or create a chart, depending on how you best learn. 

• Iron absorption (Vitamin C, Calcium, Copper)

  • Vitamin C: enhances heme iron absorption

  • Calcium: binds to iron and inhibits absorption 

  • Copper: copper-dependent enzymes (ceruloplasmin) needed for iron transport

• Bone health (Calcium, Vitamin D, Magnesium, Vitamin K, Vitamin A)

  • Calcium: provides structure to bone

  • Vitamin D: (S) enhances calcium absorption

  • Magnesium: (S) helps activate D and regulate calcium; (A) High calcium intake can reduce magnesium absorption

  • Vitamin K2: (S) helps direct calcium

  • Vitamin A: (A) too much antagonizes Vitamin D, which can reduce calcium deposition in bone

• Mineral competition 

  • Zinc & Copper: high zinc intake induces copper deficiency (causes copper trapping)

  • Iron & Zinc: compete for absorption

• Electrolyte balance 

  • Sodium & Potassium: high sodium intake increases excretion of potassium

  • Magnesium & Potassium: magnesium stabilizes the pump that helps potassium enter the cell; if magnesium is low, hypokalemia can occur

• Methylation (Folate, B12, B6, Choline, B3)

  • These B vitamins all work together for methylation. 

  • Folate & B12: Supplementation of one without the other can mask the deficiency of the other. 

  • B6 & B3: cofactor for enzymes in transulfuration and methylation, which impact how well B9 and B12 can do their jobs

  • Choline: activates back up pathway, especially when B9 or B12 is insufficient

If you master the above content, I think you’re likely to hit most areas that might be covered on the exam. 

What Else Can I Do?

If you have time, and you love a deep dive, you can consider spelling things out in another more detailed way. Here I’ve taken the category of Bone Health and I’ve included a lot of nutrients that play a role as a way to build a deeper web of understanding. You can add more detail to this.

Bone Health & Nutrient-Nutrient Interactions

Bone health isn’t just about calcium! 

• Calcium provides the structure.

  • (S) Synergistic partners: Vitamin D, Vitamin K, Magnesium

  • (A) High Phosphorus causes parathyroid to increase, which then increases bone resorption to restore the Ca:P ratio in blood. (result: bone demineralization) 

  • (A) Oxalates can bind calcium in the intestines

  • (A) Sodium and calcium share renal transport systems, so a high sodium intake increases urinary calcium excretion (calciuria).

• Vitamin D ensures absorption. (S)

  • (S) Synergistic partners: Calcium, Magnesium, Vitamin K

• Magnesium helps activate D and regulate calcium.

  • (A) But high calcium intake can reduce magnesium absorption, which can further worsen calcium utilization and weaken bones. 

• Vitamin K2 directs calcium into bone.

• Vitamin A supports remodeling in small amounts.  

  • Excess antagonizes vitamin D, leading to reduced calcium deposition in bone

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Preparing for the CNS exam? Looking for CNS test questions? Test your knowledge with our 10 practice CNS exam questions.