Their time is (past) up: Vitamin D & omega-3 supplements

 - Jennifer Middleton, MD, MPH

Recent evidence continues to challenge the routine use of two common supplements: vitamin D and omega-3 fatty acids.

A quick web search on vitamin D finds Mayo Clinic, UpToDate, and WebMD all extoling its benefits despite a lack of evidence to support its widespread use. Dr. Lin asked on the blog in 2016, "Is Vitamin D supplementation is good for anything?" Although there are a few clinical situations where vitamin D supplementation may be indicated (chronic kidney disease with secondary hyperparathyroidism, for example), vitamin D does not otherwise support mood or reduce the risk of osteoporotic fracture. An ancillary study of VITAL (Vitamin D and Omega-3 Trial) published last month in the New England Journal of Medicine randomized nearly 26,000 middle and older aged community-dwelling adults and found no benefit to vitamin D supplementation regarding fracture risk:

VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n−3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. 

An accompanying NEJM editorial declares VITAL's ancillary analysis a "decisive verdict on vitamin D supplementation." Of note, the original VITAL found no benefit for vitamin D to reduce the risk of cancer or cardiovascular disease (CVD), and it found no reduction in CVD from use of omega-3 fatty acid supplementation, either.

Another trial, REDUCE-IT, published in 2019 did find CVD benefit to omega-3 supplementation (specifically, 2 grams of icosapent ethyl daily) in persons with "elevated triglyceride levels despite the use of statins," but REDUCE-IT's findings are now being called into question. A recently published biomarker substudy found that REDUCE-IT's placebo, a pharmaceutical grade mineral oil capsule, may have increased CVD event risk among participants in the placebo group, creating a false appearance of benefit in the intervention group. These unintended harms from the study's placebo may explain why REDUCE-IT purportedly found benefit when multiple, large, previous studies have not. Like vitamin D, however, omega-3 fatty acid supplements continue to be used by millions of persons in the United States.

Changing clinical habits can be challenging. In this 2018 AFP editorial, Drs. Ebell, Shaughnessy, and Slawson describe several factors that contribute to this difficulty including practice inertia, emphasis on inductive (instead of patient-oriented, evidence-based) reasoning in medical training, and limited advertising for changes that don't benefit medical and/or pharmaceutical industries. They urge "physicians [to] accept that change is uncomfortable" and remind us that "[w]e need to remain flexible in our thinking if we are to meet our goal of doing our best when caring for every patient."

If you'd like to read more, this 2021 AFP Putting Prevention into Practice article reviews the current United States Preventive Services Task Force (USPSTF) "I" statement for vitamin D screening, and this 2019 AFP Medicine By the Numbers article reviews The NNT Group "red" rating for omega-3 fatty acid supplementation to prevent CVD.

Back to school & back to sleep: melatonin supplementation in children

- Lilian White, MD

As the end of summer approaches, children are making their way back to into the classroom. With this transition and possible changes in sleep-wake schedules, sleep disorders in children and adolescents may become more apparent. Parents may ask about the use of melatonin to treat insomnia during this transitional period.

Normal sleep duration and sleep patterns change as children age. Children 5 to 12 years old usually require 9-12 hours of sleep, and only 5 in 100 need daytime naps. Adolescents typically need 8-10 hours of nighttime sleep. Daytime napping in adolescents suggests insufficient sleep at night or a potential sleep disorder. Most high school students do not get enough sleep. This lack of sleep is associated with an increased risk of obesity, diabetes mellitus, injuries, poor mental health and attention/behavioral problems.

About 10-30% of children struggle with insomnia. Children may have difficulty initiating or maintaining sleep. They may be diagnosed with an insomnia disorder if this occurs at least 3 times per week for at least 3 months. Childhood insomnias are characterized as difficulty with sleep-association (e.g., require caregiver to be present to fall asleep) or limit-setting (e.g., absence of a regular bedtime routine). Behavioral interventions are considered first line treatment. In the Choosing Wisely campaign, the American Academy of Sleep Medicine recommends not prescribing medications to treat behavioral childhood insomnia.

Adolescents are more commonly affected by delayed sleep phase syndrome, a subtype of circadian sleep rhythm disorder. The prevalence is estimated to be 7-16%. Sleep onset and awakening are delayed by more than 2 hours for at least 3 months. A sleep diary may be helpful in making this clinical diagnosis. The most powerful influence on the circadian rhythm is light. Decreased morning light exposure and/or increased evening light exposure may worsen symptoms. Treatment of delayed sleep phase syndrome includes regular sleep-wake schedules, avoiding bright or blue light prior to bedtime, bright light therapy within the first 1-2 hours of awakening, and melatonin.

Melatonin helps the onset of sleep in the circadian rhythm. Melatonin is typically recommended at a dose of 0.3 to 5 mg taken 1.5 to 6.5 hours before bed for a short duration (i.e. days). Ideally, melatonin moves sleep onset earlier. However, if taken later – such as the middle of the night or at bedtime – it may move sleep onset later. Melatonin may be particularly helpful in children with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder and autism if behavioral approaches are insufficient to improve insomnia.

Melatonin is generally well-tolerated. Adverse effects most commonly include headache, daytime sleepiness, dizziness, and nausea. The effects of long-term melatonin use in children are not well established; low-quality evidence suggests that it may affect the timing of puberty through potential downstream effects on sex hormones. More research is needed to explore this relationship.

Although melatonin may be purchased over the counter in the United States, it may be harmful if ingested at unintended high doses. Over the past few years, physicians have seen an increase in melatonin given to children, with one study noting a 7x increase. Poison control centers have reported an 530% increase in calls regarding melatonin ingestion (94% of which were unintentional). Melatonin is available in many child-friendly forms such as gummies or chewables. If melatonin use is recommended, physicians should caution parents to store melatonin in a safe place away from children.

While melatonin may present a helpful option to treat certain sleep disorders in children, behavioral interventions are still considered the most effective and first-line treatment. Additional tips for behavioral management of insomnia can be found in a recent AFP article on Common Sleep Disorders in Children and related patient education.

Guest post: A call for family physicians’ role in combating misinformation

- Alex McDonald, MD, FAAFP, CAQSM 

For years, physicians have been discouraged from sharing information in the social media space, and, as a result, misinformation and disinformation has flourished.  Over half of younger adults get much, if not all, of their news and information from social media. Those individuals who get their information via social media channels are often only exposed to information that further aligns with their or their social circle’s own views. This phenomenon has real world consequences when it comes to an individual’s beliefs and subsequent health decisions. The average person spends 2 hours a day on social media, yet only 15 minutes four times a year with their physicians; as such, it can be challenging for physicians to correct health misinformation.

 

The COVID-19 pandemic has thrust this problem into the spotlight, leaving no easy answers or solutions. Drs. Shahjahan’s and Pasquetto's AFP editorial on “Countering Medical Misinformation Online and in the Clinic” is an excellent summary of the challenge of misinformation, both in the traditional medical setting and on social media, and also provides suggestions about how to combat it. Physicians are one of the most trusted and respected professions, and we no longer can ignore or avoid correcting or addressing misinformation when we confront it in the clinic or online. We must educate ourselves and our colleagues to learn the skills and understand the importance of consistent yet respective discourse with patients. We can no longer afford to simply avoid disagreement in the exam room or online.  These conversations are not always easy and often do not occur in a single setting, but speaking up and consistently correcting misinformation by all physicians can and will have an impact. 

 

The Federation of State Medical Boards made a strong statement in June 2021 condemning and threatening sections against licensed medical professionals who spread misinformation, yet there has been a noticeable lack of action, even for the most egregious offenders. I believe that health professionals spreading misinformation and disinformation are the most harmful and the hardest to address. As a medical community, we must find the will to confront colleagues or other medical organizations that are touting anecdotal or non-evidenced based information. There is not always a single right answer in medicine, but there are clearly wrong answers. We must not allow others to corrupt or misrepresent science for their own benefit, and we must not allow this to propagate or the trend to continue. There is often debate within the medical literature, and often evidence-based medicine begins with anecdote or case studies, but we must not mistake early emerging information, that warrants further investigation, with evidence-based science.  

 

Physicians, who specialize in relationships, trust, and understanding, are best equipped to tackle this challenge. Collaboration, connection, and compassion are all are key - who better to do this work than family physicians? A strong and trusted social media account is a tool in the bag of the 21st century physician to share accurate and trusted information beyond the walls of the clinic or hospital. We must each also acknowledge our own role in inadvertently spreading misinformation. We are human and we are all susceptible to the emotions and bias on which misinformation thrives. We must educate ourselves to spot misinformation when we see it, and not just hit the “like” or “share” button, to stop misinformation in its tracks. We must not comment or engage with misinformation as this only boosts its reach; instead, ignore, block and move on.

No single person or approach is going stem the tide of pervasive misinformation and disinformation. It’s going to take all of us to educate ourselves, our colleagues, and our patients. 

 

Additional Resources: 

UNICEF - https://www.unicef.org/eca/media/13636/file 

Washington Post - https://www.washingtonpost.com/lifestyle/2021/02/24/doctor-nurse-online-vaccine-rumors/ 

MisinforRx - https://misinforx.com/resources/ 

Health and Human Services - https://www.hhs.gov/sites/default/files/health-misinformation-toolkit-english.pdf 

World Health Organization - https://www.who.int/docs/default-source/coronaviruse/vaccine-misinformation-toolkit_desktop1.pdf?sfvrsn=1da119fb_1&download=true 

 

Gestational diabetes is an increasingly common pregnancy complication

 - Kenny Lin, MD, MPH

A recent report from the Centers for Disease Control and Prevention documented a precipitous rise in the rate of gestational diabetes in the U.S. from 2016 to 2020, based on data collected from birth certificates. In 2020, gestational diabetes affected 7.8% of all pregnancies, reflecting a 13% increase since 2019 and a 30% increase since 2016. Prevalence increased with increasing age (2.5% in patients younger than 20 years and 15.3% in those aged 40 or older) and increasing pre-pregnancy body mass index (BMI). Both factors are likely driving the overall rise in gestational diabetes; the median age at which U.S. women gave birth reached an all-time high of 30 years in 2019 and only 2 in 5 women with a live birth in 2020 had a normal BMI prior to pregnancy.

The U.S. Preventive Services Task Force (USPSTF) recommends screening for gestational diabetes in asymptomatic pregnant patients at or after 24 weeks of gestation. Although the USPSTF did not identify a preferred test, a previously discussed study suggested that the two-step approach (a non-fasting 50 gram oral glucose challenge test followed by a fasting 100 gram glucose tolerance test if the first test is positive) "produces equivalent benefits, and fewer harms, than the one-step approach."

Adverse outcomes associated with gestational diabetes include gestational hypertension, preeclampsia, shoulder dystocia, macrosomia, and Cesarean delivery. Gestational diabetes also confers a 7-fold greater maternal risk of developing type 2 diabetes later in life and 1.5 times greater risk of the child being overweight in childhood or adolescence. Management of gestational diabetes begins with glucose self-monitoring and lifestyle modifications, followed by oral medication or insulin if target blood glucose levels are not achieved.

Prevention of gestational diabetes includes counseling on appropriate weight gain goals based on pre-pregnancy BMI, which can generally be achieved by averaging "350 to 450 calories per day above the previous intake (e.g., two slices of bread with half an avocado, ¾ cup of Greek yogurt or 1 cup of blueberries with two hard-boiled eggs)." Additionally, "patients should be encouraged to engage in moderate aerobic activity most days of the week for at least 20 to 30 minutes at a time, for a total of at least 150 minutes per week." In a previous AFP Community Blog post, Dr. Erin Fredrickson discussed strategies for facilitating exercise in pregnant patients. The USPSTF recommends offering behavioral counseling interventions for healthy weight and weight gain in pregnancy; effective interventions generally started at the end of the first trimester and varied in duration and intensity (from 15 to 120 minutes and from 1 to more than 12 total contacts).

Will vaccine hesitant US adults accept a more traditional COVID-19 vaccine?

 - Jennifer Middleton, MD, MPH

Earlier this month, the United States (US) Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Novavax for adults aged 18 and older:

The Novavax COVID-19 Vaccine, Adjuvanted is administered as a two-dose primary series, three weeks apart. The vaccine contains the SARS-CoV-2 spike protein and Matrix-M adjuvant. Adjuvants are incorporated into some vaccines to enhance the immune response of the vaccinated individual.

This technology is similar to more traditional vaccines, such as the influenza vaccine, and differs from the available mRNA COVID-19 vaccines from Pfizer and Moderna. It's currently authorized as a 2 shot series, with doses given 3 weeks apart. In the clinical trial data of 25,500 participants submitted to the FDA, Novavax reported that 2 doses of their vaccine were, overall, "90.4% effective in preventing mild, moderate or severe COVID-19....in the subset of participants 65 years of age and older, the vaccine was 78.6% effective." Several countries worldwide who have previously authorized the Novavax vaccine offer a booster 5 months after the 2nd shot, and Novavax is reportedly pursuing authorization in the US for both that booster as well as administration to adolescents aged 12-17. They are also testing boosters with protection against the omicron strain. Although Novavax was part of the US government's Operation Warp Speed in 2020, the company suffered "developing and manufacturing setbacks" as a smaller start-up which put it behind Pfizer and Modera in the race to an EUA. 

The speed of the mRNA vaccines' development, along with the newness of their technology, led some people to question their short- and long-term safety. Given this reluctance regarding mRNA vaccines, Novavax, which "has no genetic material, only proteins," may be a more comfortable option for some patients. Approximately 10% of the adult population in the US has yet to receive a first dose of any of the COVID-19 vaccines, and increasing vaccine uptake may help slow the development of new variants. 

As noted on the blog last year, helpful resources to discuss vaccine hesitancy with patients include these resources and talking points from the US Centers for Disease Control and Prevention (CDC) along with this article on "Helping Patients Make Healthy Decisions on COVID-19" found in the AFP By Topic on Coronavirus Disease 2019 (COVID-19).