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CME / ABIM MOC / CE

Does High Dietary Zinc Reduce Migraine Risk?

  • Authors: News Author: Jennie Smith; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 3/10/2023
  • Valid for credit through: 3/10/2024, 11:59 PM EST
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

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Target Audience and Goal Statement

This activity is intended for neurologists, family medicine/primary care clinicians, internists, nurses, pharmacists, physician assistants, and other members of the health care team for patients with migraine.

The goal of this activity is for learners to be better able to describe the relationship between dietary zinc intake and migraine, based on a cross-sectional study of US National Health and Nutrition Examination Survey data from 1999 to 2004.

Upon completion of this activity, participants will:

  • Assess the relationship between dietary zinc intake and migraine, based on a cross-sectional study of National Health and Nutrition Examination Survey data from 1999 to 2004
  • Evaluate the clinical implications of the relationship between dietary zinc intake and migraine, based on a cross-sectional study of National Health and Nutrition Examination Survey data from 1999 to 2004
  • Outline implications for the healthcare team


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News Author

  • Jennie Smith

    Freelance writer, Medscape

    Disclosures

    Jennie Smith has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Does High Dietary Zinc Reduce Migraine Risk?

Authors: News Author: Jennie Smith; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 3/10/2023

Valid for credit through: 3/10/2024, 11:59 PM EST

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Clinical Context

Worldwide prevalence of migraine is approximately 1 billion. The 2016 Global Burden of Disease study showed that it is the second most common cause and the most common neurological cause of disability.

Neuroinflammatory and oxidative stress have been implicated in the pathogenesis of migraine. Zinc, an anti-inflammatory and antioxidant trace element, is a cofactor for antioxidant enzymes that plays a key role in neuronal signaling.

Study Synopsis and Perspective

People with higher dietary zinc intake have a nearly one third lower risk for migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the US National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake compared with people without migraine.[1] The data used in the analysis were collected between 1999 and 2004 and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.

An Inverse Relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption, as inferred from foods eaten. They also considered zinc supplementation, for which data were available for 4324 participants, of whom 2607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing the lowest risk for migraine (odds ratio [OR], 0.70; 95% CI, 0.52-0.94; P=.029) compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk for migraine was lower still, to between an OR of 0.62 (95% CI: 0.46-0.83; P=.019) and an OR of 0.67 (95% CI, 0.49-0.91; P=.045).

Although the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.

The Importance of Nutritional Factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr Friedman cited a recent study showing that vitamin B12 and magnesium supplementation in women, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain, and decreased levels of calcitonin gene-related peptide.[2] A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency, and disability in women with episodic migraine.[3]

Vitamin D levels are also lower in people with migraine compared with controls, Dr Friedman noted, and a randomized trial of 2,000 IU of vitamin D3 daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use compared with placebo.[4,5] Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B6, and vitamin B1.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

Headache. 2023;63(1):127-135.

Study Highlights

  • This cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999 to 2004 included 11,088 participants (mean age, 46.5 years; 50% female), of whom 2236 (20.2%) reported severe headache or migraine in the past 3 months and were classified as having migraine.
  • Dietary zinc intake was assessed with the 24-hour dietary recall system.
  • Dietary zinc intake was generally higher among participants who were younger, males, married or living with a partner, non-Hispanic Whites, and nonsmokers.
  • It was also linked to higher educational status; lower incidence of hypertension, diabetes, stroke, and coronary heart disease; higher energy, protein, carbohydrate, and copper intake; and lower serum C-reactive protein levels.
  • On univariate analysis, age, sex, race/ethnicity, educational level, smoking, diabetes, stroke, protein intake, copper intake, and C-reactive protein were associated with migraine.
  • The analysis adjusted for age, sex, ethnicity, education level, body mass index, smoking, diabetes, cardiovascular disease, nutritional factors, and other covariates.
  • Adjusted ORs (aORs) for migraine, compared with the lowest dietary zinc intake quintile (Q1, ≤5.9 mg/day), were 0.73 (95% CI: 0.61-0.88), in Q2 (6.0-8.4 mg/day; P=.004), 0.71 (95% CI, 0.56-0.91, P=.013) in Q3 (8.5-11.2 mg/day), 0.71 (95% CI, 0.57-0.90; P=.008) in Q4 (11.3-15.7 mg/day), and 0.70 (95% CI, 0.52-0.94; P=.029) in Q5 (≥15.8 mg/day).
  • In a sensitivity analysis of 4324 zinc supplementation survey participants (2607 receiving zinc supplements), total zinc intake, but not zinc intake from supplements alone, was also associated with migraine.
  • Compared with the lowest total zinc intake quintile (Q1: 0.5-9.6 mg/day), aORs for migraine were 0.62 (95% CI, 0.46-0.83; P=.019) in Q3 (19.3-24.3 mg/day) and 0.67 (95% CI, 0.49-0.91; P=.045) in Q4 (24.4-32.5 mg/day).
  • The investigators concluded that among adult Americans, dietary zinc intake is inversely and robustly associated with migraine, based on sensitivity analyses.
  • This suggests that zinc is an important nutrient that affects migraine, which is biologically plausible, given the antioxidant and anti-inflammatory properties of zinc.
  • Migraine disease is thought to result from oxidative stress levels exceeding the capacity of antioxidants within the body to reduce that stress.
  • Superoxide dismutase, a key antioxidant enzyme, contains zinc as a structural component and is consistently reduced in individuals living with migraine.
  • Zinc deficiencies may hinder superoxide dismutase synthesis and contribute to oxidative stress.
  • Sources of dietary zinc include seafood (especially oysters), poultry, red meat, whole grains, nuts. legumes, and dark chocolate.
  • Recommended daily dosage of zinc is 9.5 mg for men and 7 mg for women, which is usually achieved in most dietary patterns.
  • Vegetarians, vegans, pregnant or breastfeeding women, and adults aged at least 65 years may require zinc supplementation.
  • Other nutritional factors linked to migraine include low magnesium, B12, vitamin D, and alpha-lipoic acid levels.
  • Magnesium supplementation is a recommended preventive treatment for migraine, and alpha-lipoic acid supplementation may lower migraine severity, frequency, and disability in women.
  • A recent study showed that women given vitamin B12 and magnesium supplementation and high-intensity interval training had less migraine pain, inflammation signaling pathway activity, and calcitonin gene-related peptide levels.
  • Study limitations included cross-sectional design, precluding causal inferences; use of a broad question to determine migraine prevalence; and possible lack of generalizability beyond Americans aged at least 20 years.
  • Future prospective studies are therefore needed to confirm and clarify effects of dietary zinc intake on migraine.

Clinical Implications

  • Among adult Americans, dietary zinc intake is inversely and robustly associated with migraine, based on sensitivity analyses.
  • This suggests that zinc is an important nutrient that affects migraine, which is biologically plausible, given the antioxidant and anti-inflammatory properties of zinc.
  • Implications for the Health Care Team: Members of the healthcare team should provide education on sources of dietary zinc to patients that may benefit from supplementation.

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