Wellness Check: Nutrition

2 Minute Medicine is pleased to announce that we are launching Wellness Check, a new series dedicated to exploring new research evidence focused on wellness. Each week, we will report on articles examining different aspects of wellness, including (but not limited to) nutrition, sleep, reproductive health, substance use and mental health. This week, we explore the latest evidence-based updates in nutrition. 

More omega-3 and less omega-6 fatty acid consumption associated with reduced migraine frequency and severity

1. Diet with higher levels of omega-3 fatty acid and lower omega-6 fatty acid decreased incidence and severity of migraines in participants with chronic and episodic migraines.

2. Changing dietary fatty acid intake also led to changes in circulating levels of oxylipins (lipid mediator that regulates pain).

Evidence Rating Level: 1 (Excellent)

Fatty acids play an important role in migraine pathogenesis due to their conversion into oxylipins (lipid mediators that regulate pain). Interestingly, omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have pain reducing properties, whereas omega-6 fatty acids (such as linoleic acid) have pain promoting properties. However, whether changes in dietary fatty acids can effectively modulate pain in patients with migraines has not been tested.

In this randomized controlled trial, 182 adult participants (88% women) with chronic and episodic migraine were randomized into 3 different diets with varying amount of EPA, DHA, and linoleic acid for 16 weeks. 61 participants were put on H3 diet (increasing EPA+DHA to 1.5g/day), 61 participants on H3-L6 diet (increase EPA+DHA and concurrent reduction in linoleic acid) and 60 participant in control diet containing average amounts of EPA, DHA and linoleic acid in the United States. Patients who were pregnant, breastfeeding, with history of head trauma or surgery, or used fish oil as supplements were excluded. The primary endpoints were blood oxylipin levels, frequency of headaches, and impact on quality of life.

Patients on both the H3-L6 and H-3 diet had increased circulating oxylipin 17-hydroxydocosahexaeonic acid levels (associated with pain reduction) as well as decreased total headache hours per day. Interestingly, patients on H3-L6 diet also had decreased use of NSAIDs or aspirin compared to control. However, both H3-L6 and H3 diet did not lead to significantly changed quality of life compared to control diet. This study was limited by the small study population and short study period. Nonetheless, the significant changes in quantitative measures such as headache frequency and severity highlight the potential for dietary fatty acid to be tested as adjunct migraine therapy.

 Moderate coffee consumption may be inversely associated with risk of arrhythmias

1. Greater amount of moderate, habitual coffee consumption was associated with lower risk of arrhythmia.

2. Genetic differences in caffeine metabolism did not modulate effect of coffee consumption on risk of arrhythmia. 

Evidence Rating Level: 2 (Good)

Coffee is widely consumed and has been thought to increase risk of arrhythmia. However, whether moderate, habitual coffee intake is associated with risk of arrhythmia has not been clearly documented.    

This prospective cohort study assessed association between daily coffee intake and rate of cardiac arrhythmias in adults aged 40-69 years using UK Biobank data. 386,258 adults were followed from 2006 to 2018, with coffee intake measured through participant questionnaires. Participants who were pregnant, with pre-existing arrhythmias, or self-withdrew from the study were excluded. The primary outcome was rate of arrhythmias in general (atrial fibrillation, atrial flutter, supraventricular tachycardia, premature atrial complexes, and premature ventricular complexes). Secondary outcomes assessed the rate of each type of these arrhythmias alone. Lastly, DNA was collected from participants at initial assessment to determine whether genetic differences in caffeine metabolism modulated association between coffee intake and arrhythmias (assessed via mendelian randomization studies).

During the study period, 16,979 participants developed arrhythmias. Each additional cup of habitual coffee (up to 8 cups) consumed was associated with a 3% lower risk of incident arrhythmias (hazard ratio 0.97, 95% CI, 0.96-0.98; p<0.01). Moreover, there was no evidence for genetic variants on caffeine metabolism modulating this effect. However, there were limitations noted in this study. Since this study was based on self-reporting, the accuracy in capturing amount and changes in pattern of coffee consumption might be limited. Nonetheless, this study was significant as it offered evidence towards debunking the prior held assumption that coffee intake is associated with arrhythmias.

Ranitidine may not lead to significant increase in N-nitrosodimethylamine in healthy adults

1. Ranitidine consumption did not result in higher urinary excretion of N-nitrosodimethylamine (NDMA) compared to placebo.

2. High nitrite diet increased urinary excretion of NDMA.

Evidence Rating Level: 1 (Excellent)

In 2020, ranitidine, a histamine 2 receptor blocker widely used as heartburn treatment, was removed from market due to concern over amount of carcinogen N-nitrosodimethylamine (NDMA) found in certain lots. Aside from potential contamination during manufacturing, ranitidine can form NDMA in humans during the process of degradation, especially in the presence of nitrites. However, whether a substantial amount of NDMA is produced after consumption of ranitidine and a nitrite-rich meal has not been shown.

In this randomized controlled trial, 18 healthy adults aged 28-43 were fasted overnight and received either ranitidine (300mg) or placebo alongside a breakfast high or low in nitrite. The study was conducted in a clinical pharmacology unit in West Bend, Wisconsin, during the months of June and July of 2020. Participants who consumed nicotine-containing products, had significant past medical history, or had used any prescription of non-prescription medication within 14 days of screening were excluded. The primary outcome was 24hr urinary excretion of NDMA.

There was no statistically significant difference between ranitidine and placebo group in 24hr urinary excretion of NDMA with (paired difference -1.1ng, P=0.71) or without (0ng p-0.54) high-nitrite diet. Additionally, there were no difference in plasma NDMA level in ranitidine or placebo group. Although this was reassuring regarding the potential safety of ranitidine, this study was limited in its generalizability since it was not conducted with patients with gastric disease, whose stomach pH may result in slightly altered metabolism of ranitidine. Therefore, further studies with larger cohort, in patients with gastric disease, and with longer-term use of ranitidine is still necessary. Nonetheless, this study was significant in establishing more physiological parameters for future testing of NDMA formation from ranitidine or other medications.

Image: PD

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