Children's brains have high metabolic demands that change as their brains mature, but whether nutrition during pregnancy can influence this developmental pattern years later is not well understood. A new study tested whether omega-3 fatty acids from fish oil taken during pregnancy could influence this process.

Researchers followed children whose mothers had participated in a Danish randomized trial of omega-3 supplementation during pregnancy. From pregnancy week 24 until one week after birth, the women received capsules containing either 2.4 grams per day of long-chain omega-3 fatty acids (55% EPA and 37% DHA) or olive oil as a placebo. When the children were about 10 years old, the families were invited to return for assessments of the children's cognition, mental health, and brain metabolism. A total of 487 children underwent brain imaging, and 460 had usable data for at least one of three measures of brain metabolism, including whole brain blood flow, whole brain oxygen use, and lactate levels in one brain region as a marker related to glucose metabolism. The researchers then used this information to examine whether prenatal omega-3 supplementation was associated with differences in brain metabolism, and whether the brain metabolism measures were associated with mental health or cognition. They also compared the children's brain metabolism measures with data from 248 adults in earlier studies to see how they differed with age.

• The adults had lower brain blood flow, oxygen use, and lactate levels than the children, consistent with the decline in brain metabolism that occurs as the brain matures.
• Children in the prenatal omega-3 group had on average about 2.5% lower whole brain blood flow and about 8% lower brain oxygen use at rest than those in the placebo group. Lactate did not clearly differ between groups.
• The three brain metabolism measures were not clearly related to ADHD or autism diagnoses, parent-rated cognitive skills involving planning and self-control, or intelligence.
  
• Differences in snapshots of omega-3 blood levels did not clearly track with differences in brain metabolism. Higher maternal omega-3 levels before supplementation and higher omega-3 levels in the children at age 10 were not clearly associated with any of the children's three brain metabolism measures.

During childhood, the brain has high metabolic demands as it builds and refines neural connections and develops the insulating myelin around nerve fibers. These demands are reflected in brain blood flow and oxygen use, which rise through early childhood, peak around middle childhood, and then generally decline as the brain matures. Omega-3 fatty acids may influence this developmental process in several ways. DHA becomes part of the membranes surrounding brain cells, where it can affect how those membranes and their signaling proteins function, while EPA and DHA can also influence inflammatory signaling in the brain. Both pathways can influence how much energy brain cells use, providing a plausible link to the lower blood flow and oxygen use seen in the prenatal omega-3 group.

A key limitation is that brain metabolism was measured only once, so the study cannot show when the differences emerged or how they changed over time. The effects were also small, and brain metabolism measures can vary widely among children, which may make subtle differences harder to detect. Nevertheless, the findings suggest that prenatal omega-3 supplementation may influence later brain biology, making it worth discussing as part of routine pregnancy care. In Aliquot #100, I discuss factors that influence child development before conception, during pregnancy and infancy, and into the toddler and early childhood years.

Hormonal changes during and after menopause have wide-ranging effects on health. A new cross-sectional study examined whether hormone replacement therapy (HRT) was associated with better cognitive performance in older women.

The researchers analyzed existing data from 1,374 women aged 60 or older who took part in one of two rounds of a U.S. national health survey. They compared women who reported ever using estrogen, progesterone, or both for menopause with women who reported never using HRT. They also calculated the number of years from each woman's first period to menopause as a rough proxy for the length of her natural estrogen exposure during the reproductive years. The women completed cognitive tasks that assessed verbal learning and memory by having them learn and later recall a list of words, verbal fluency by asking them to name as many animals as possible in one minute, and mental speed, attention, and working memory by having them match numbers with symbols as quickly and accurately as possible.

• HRT was linked to better verbal learning and memory and better verbal fluency, while an initial association with better performance on the task measuring mental speed, attention, and working memory was no longer statistically clear after women with missing survey information were excluded.
• The number of years between the first menstrual period and menopause was initially linked to better verbal learning and memory, but this association also did not hold after women with missing survey information were excluded. There were no clear links with verbal fluency, mental speed, attention, or working memory.
• Exploratory age-based analyses suggested that the apparent separation in cognitive performance between HRT users and non-users was greatest around ages 65 to 70. However, the finding does not mean that starting HRT around ages 65 to 70 would lead to better cognitive outcomes.

Estrogen can cross the blood-brain barrier and bind to estrogen receptors in several brain regions, including the hippocampus, which plays an important role in memory. Estrogen signaling influences several processes involved in brain function, including energy use, inflammatory responses, and blood flow in the brain. As estrogen levels fall after menopause, these processes may change in ways that affect a range of cognitive abilities. Estrogen-containing HRT could partly restore estrogen signaling and help support brain function.

Because each woman was assessed only once, the study cannot prove that HRT caused better cognitive performance or slowed cognitive decline. The survey also did not record the type, dose, timing, or duration of HRT. Taken together, the findings suggest that cognitive health may be worth considering in discussions about HRT and that further research is warranted. In Q&A #61, I discuss whether women should start taking hormone replacement therapy before menopause.

Physical activity guidelines recommend 150–300 minutes of moderate or 75–150 minutes of vigorous activity per week, but it remains unclear whether short bursts spread throughout the day are linked to long-term benefits similar to longer bouts of exercise. A new study examined how these different activity patterns were associated with the risk of death and cardiovascular disease.

The study included 96,054 middle-aged and older adults from the UK Biobank, with an average age of 62. Researchers used seven days of data from wrist-worn activity trackers to estimate how much moderate-to-vigorous physical activity (MVPA) each person accumulated in short bursts of less than 10 minutes versus longer stretches of about 10 minutes or more. They then examined how the amount of activity accumulated in each activity pattern was associated with the risk of death from any cause and new cardiovascular disease events over about eight years, while accounting for major demographic, health, and lifestyle factors. For each activity pattern, the researchers compared higher amounts of activity with the level separating the least-active 10% of participants from everyone else.

• Compared with a reference level of 65 minutes a week of brief MVPA, 150 minutes a week was associated with a 48% lower rate of death from any cause and a 33% lower rate of new cardiovascular disease events. Adding more brief activity beyond 150 minutes was linked to little additional reduction in either outcome.
• Compared with a reference level of 38 minutes a week of MVPA accumulated in longer bouts, 300 minutes a week was associated with a 49% lower rate of death from any cause and a 35% lower rate of new cardiovascular disease events. Unlike brief activity, the association continued beyond 300 minutes.
• At high levels of brief MVPA, more activity accumulated in longer MVPA bouts was still linked to lower rates of death and cardiovascular disease. But at high levels of longer MVPA, adding brief activity beyond about 150 minutes a week was linked to little further difference in risk.

Studies of short activity breaks have shown improvements in blood pressure and blood glucose, demonstrating that activity does not have to be sustained for long periods to benefit cardiovascular and metabolic health. Longer activity bouts can provide the same benefits while keeping cardiovascular and metabolic demands elevated for longer. This may create a stronger training stimulus and promote additional adaptations, particularly improvements in cardiorespiratory fitness, the ability of the heart, lungs, and circulation to support prolonged activity.

The findings are observational and are based only on a short snapshot of participants' physical activity habits, so they cannot prove that brief or longer activity caused the differences in death and cardiovascular disease risk. Even so, the study suggests that brief bouts of MVPA can provide substantial health benefits, while they may not fully replace exercise sustained for longer periods. In this clip, I discuss how exercise timing, type, and frequency impact heart aging and long-term cardiovascular health.