Drug & supplement interaction

Zone Diet + Leucovorin Calcium

Leucovorin Calcium brand name: Wellcovorin.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Zone Diet and Leucovorin Calcium in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Zone Diet and Leucovorin Calcium

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Leucovorin Calcium and Zone Diet in our sources. This does not guarantee that the combination is completely free of risk — research on Zone Diet alongside specific medications may be limited.

Worth understanding: our licensed dataset holds no drug-interaction record for Zone Diet at all — not against Leucovorin Calcium, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

Zone Diet is an eating pattern rather than something you take. Ask your pharmacist or doctor before changing how you eat while on a prescribed medicine: some medicines are dosed around meals, and a change in diet can change how they work. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Zone Diet safety at a glance

Zone Diet overall Use caution Generally safe for healthy adults but it is restrictive and may not suit everyone.
Pregnancy Use caution Calorie- or carb-restricted diets may not meet pregnancy nutrient needs, so check with your doctor first.
Breastfeeding Use caution Nursing needs extra calories and nutrients, so discuss any restrictive diet with your provider.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Leucovorin Calcium and Zone Diet? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

What Leucovorin Calcium’s Own FDA Label Lists

This is not an interaction — none of it involves Zone Diet. These are the most notable effects listed in the ADVERSE REACTIONS section of Leucovorin Calcium’s own FDA label, for the medication by itself. Knowing the drug’s own list makes it easier to work out the likely cause if something new turns up while you follow Zone Diet and take the medicine. 5 of them are worth acting on rather than waiting out — marked below.

  • A low white blood cell count Worth acting on mentioned in 5.8% of FDA reports for Leucovorin Calcium
  • A low platelet count Worth acting on
  • Kidney problems Worth acting on
  • Hives Worth acting on
  • A higher chance of infection Worth acting on
  • Mouth irritation or sores
  • Hair loss
  • Reduced appetite
  • Constipation
  • Diarrhea mentioned in 9.5% of FDA reports for Leucovorin Calcium

Showing the 10 most notable of 14 label-listed effects — ranked by how unusual each one is across medicines generally, with serious effects weighted up.

From the ADVERSE REACTIONS section of the FDA label for Leucovorin Calcium. Read the label on DailyMed › Where a percentage is shown, it is the share of 19,003 voluntary FDA FAERS reports for Leucovorin Calcium that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Zone Diet’s licensed record lists no adverse effects our clinical vocabulary could match, so there is no Zone Diet side to compare — that is a limit of the record, not a statement that Zone Diet has no side effects.

Everything else you take

See Every Supplement That Interacts With Leucovorin Calcium

This page covers Zone Diet only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Leucovorin Calcium page lists 17 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Coffee Charcoal (moderate), European Mandrake (moderate), Glucomannan (moderate) and Guar Gum (moderate).

By severity: 1 major · 7 moderate · 9 minor.

Open the Leucovorin Calcium interaction page

How much people look this up

Where Zone Diet and Leucovorin Calcium Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Zone Diet
Steady interest

#1,317 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Leucovorin Calcium
Top 25%

#649 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Zone Diet reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Zone Diet and Leucovorin Calcium records this page draws on were last updated June 22, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Eating pattern

About Zone Diet

What is Zone Diet?

  • Weight loss
  • Blood sugar control
  • Reducing inflammation
  • Heart health support
  • Improving energy and athletic performance

The Zone Diet is an eating plan, not an herb or supplement, that aims to balance every meal into roughly 40% carbohydrate, 30% protein, and 30% fat. It can help some people lose weight and improve diet quality, mostly by encouraging portion control and lean proteins, but evidence that its specific ratio is better than other balanced diets is limited. Talk with your doctor, pharmacist, or a dietitian before starting, especially if you have a medical condition.

Eating plan (whole-food meals and snacks), meal-delivery services, prepackaged bars and shakes

An interaction check asks whether these two react with each other — it does not ask whether Zone Diet is a good idea for someone in your situation. Here is what our Zone Diet record says about it on its own.

Zone Diet: dosing

There is no pill or standardized "dose" for the Zone Diet because it is an eating pattern, not a supplement. Instead, the plan is followed by structuring meals around the 40% carbohydrate, 30% protein, 30% fat idea and eating regular, portion-controlled meals and snacks.If you use Zone-branded products like bars or meals, follow the label directions.

From our Zone Diet monograph — the full record covers uses, side effects and every documented interaction.

Read the full Zone Diet monograph & all interactions
Medication

About Leucovorin

What Is Leucovorin Used For?

Brand name: Wellcovorin

Leucovorin is used to reduce the harmful effects of methotrexate when the body is slow to clear it, and to counteract accidental overdoses of drugs that block folic acid (called folic acid antagonists or DHFR inhibitors). It is also used to treat cerebral folate transport deficiency (FOLR1-CFTD), a rare genetic condition that prevents the brain from receiving enough folate.

The injectable forms — including leucovorin calcium injection and Vykoura — are additionally approved for rescue after high-dose methotrexate therapy, for treatment of megaloblastic anemia (a type of anemia caused by low folic acid) when oral treatment isn't possible, and for use alongside fluorouracil in treating metastatic colorectal cancer. Leucovorin calcium injection is specifically indicated for rescue after high-dose methotrexate in osteosarcoma.

Most-Reported Side Effects for Leucovorin Calcium

From FAERS, the FDA’s public side-effect reporting system (19,003 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Diarrhea 1,799 reports
Nausea 1,388 reports
Vomiting 1,135 reports
Neutropenia 1,094 reports
Fever 1,011 reports
See full Leucovorin drug information
Keep checking

Other Drugs & Zone Diet

Browse every other medication we’ve checked against Zone Diet — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
0Moderate
0Minor
2,829No known interaction
No interaction 2,829 drugs checked — show the list
Evidence & sources

Zone Diet References

The 4 references that drive our Zone Diet monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Fontani, G., Corradeschi, F., Felici, A., Alfatti, F., Bugarini, R., Fiaschi, A. I., Cerretani, D., Montorfano, G., Rizzo, A. M., and Berra, B. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with Omega-3 polyu
  2. Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9) PubMed
  3. McAuley KA, Hopkins CM, Smith KJ, et al. Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia. 2005 Jan;48(1):8-16. Epub 2004 Dec 23. Erratum in: Diabetologia. 2005 May;48(5):1033.
  4. Jarvis M, McNaughton L, Seddon A, Thompson D. The acute 1-week effects of the Zone diet on body composition, blood lipid levels, and performance in recreational endurance athletes. J Strength Cond Res. 2002 Feb;16(1):50-7. DOI

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Following Zone Diet While Taking Leucovorin Calcium: Common Questions

Is it safe to follow Zone Diet while taking Leucovorin Calcium?
We do not list a known interaction between Zone Diet and Leucovorin Calcium. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Does Leucovorin Calcium interact with any supplements?
Yes. Leucovorin Calcium has documented interactions with 17 supplements in our database — Zone Diet is not one of them. The Leucovorin Calcium interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Leucovorin Calcium and Zone Diet?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.