By Mike Montemarano, Associate Editor11.09.21
Comprehensive data collection on sleep, an important topic for dietary supplement researchers, begins with factoring key differences in rates of sleep needs, and disorders, according to Fiona Baker, PhD, senior program director for SRI International’s Center for Health Sciences, who spoke at the Council for Responsible Nutrition’s Science in Session event in October.
“Men and women even interpret what ‘sleep quality’ means differently,” Baker said. “Women are more likely to be morning types, and tend to have shorter circadian rhythms. They have more deep sleep and less light sleep, and feel less wakefulness after sleep onset than men do.”
Women are substantially more likely to experience insomnia, which is linked to hormonal changes, and comorbidities such as anxiety and depression, Baker noted. The reproductive cycle, especially post-menopause, is also a clear differentiating factor when it comes to risks of developing sleep disorders. While research is limited when it comes to the role that diet plays in sleep, aside from certain dietary supplement ingredients such as soy isoflavones, Baker said that delineating the differences between men and women—in terms of overall sleep quality, its perceptions, and sleep hygiene—will be key in uncovering new findings on the sleep front.
Disparities During Pregnancy
Regan Bailey, PhD, MPH, professor at Purdue University’s nutritional science department, discussed contemporary knowledge of the nutritional disparities women experience during pregnancy—a key target for future research crafting public health policy for the prevention of preeclampsia, gestational diabetes, adverse birth outcomes, unhealthy birth weight, and birth defects.
While the U.S. is ahead of the curve in some aspects, such as folic acid intake, maternal dietary supplementation on the whole falls short in key areas, such as iodine, Bailey said. Only one in five women takes a prenatal supplement containing iodine, despite daily requirements near-doubling upon the onset of pregnancy, in part for the prevention of problems with a child’s neurocognitive development. Likewise, the U.S. maternal population in the U.S. is only taking 2% of the recommended daily intake (RDI) of choline.
Meanwhile, many maternal supplements contain excessive amounts of nutrients that have upper limits in RDIs, Bailey added. NHANES data suggest that women in the U.S. are at risk for taking excessive amounts of folic acid, iron, and zinc. Further adding to this risk is the fact that many women who do take supplements already take in more vitamins and minerals through their diets alone than what are needed.
Further compounding the issue, “we know next to nothing about total usual dietary intakes of lactating women,” Bailey said.
Research on the ECHO (Environmental Influences on Child Health Outcomes) finds several disparities in its cohort of mothers when it comes to risks of insufficient nutrient intake. Age is the strongest link to nutrient intake during pregnancy, Bailey said, followed by racial background, with educational attainment also correlating to usage.
Diet and the Estrogen Balance
With estrogen levels in flux throughout a woman’s life cycle, nutrition research is revealing the role that diet—within a bigger picture of healthcare—can play in maintaining balanced estrogen levels, and what beneficial health outcomes could be tied to modulating the hormone, said Zeynep Madak-Erdogan, associate professor at the University of Illinois Urbana-Champaign.
Research on the topic has been especially prevalent when it comes to botanicals such as cranberry, soy isoflavones, licorice root, and more, with hypotheses that supplementation could improve symptoms linked to estrogen loss.
Estrogens work through a wide range of pathways to affect metabolism, reproductive function, bone health, and cancer risk. While hormone replacement therapy (HRT) is currently used for more serious medical applications, Madak-Erdogan said there’s a critical need to substantiate safer alternatives to HRT to deal with metabolic health consequences. Perhaps, she said, there is an interconnected role that botanicals could play in the reduction of breast cancer, cardiovascular, and obesity risk. Phytoestrogens have a noted impact on vasculature, the makeup and deposition of adipose tissue, and obesity, which is linked to significantly higher cancer risks. While more research is needed, botanicals may serve as alternatives to HRT without presenting risks to reproductive function.
The gut microbiome may be a key target, or at least a pathway, when it comes to natural therapies which can beneficially modulate estrogen levels, Madak-Erdogan said. “Estrogens are metabolized by bacteria, and bacteria are responsible for changing the half-life of estrogens in the body,” she said, noting that changes can be so significant that pregnancies have been attributed to antibiotics changing the gut microbiome enough to interfere with oral contraceptives. Still, “we don’t know the impact of dietary estrogens on the gut microbiome, or whether changes in bacteria can impact cancer or metabolic disease outcomes,” Madak-Erdogan said.
Women’s Eye and Brain Health
Women are uniquely affected by eye health issues, and how the eye ages has been shown to have an impact on cognitive aging, according to Billy Hammond, PhD, professor in the behavioral and brain sciences program at University of Georgia.
“From a prevalence perspective, about two-thirds of macular degeneration occurs in women. Dementia is also much more prevalent in women, and there are two different tracks for how both the eye and the brain age between men and women,” Hammond said. “The age-standardized rates for cataracts, in which things in the eyes oxidize and become opaque, significantly are higher in women globally.”
As a researcher with decades of background in the carotenoids lutein and zeaxanthin, Hammond said there are significant differences in the way that men and women metabolize them.
This is especially important to reproductive health applications, Hammond said, pointing to research which monitored maternal lutein and zeaxanthin intakes and linked them to improvements in cognitive behavioral indices in children during follow-up periods lasting several years. This furthers the case that visual acuity is directly tied to cognitive performance. “Lutein levels have been shown to extend vision up to 30%,” Hammond said. “Clearing up visual signals is also known to increase the processing of those signals. Taking care of hearing and vision is shown to slow cognitive decline, and we know this because hearing aids and cataract surgeries are linked to improvements in cognition.”
With those in the highest quintiles of retinal lutein and zeaxanthin experiencing a 24% lower risk of cognitive impairment, factoring in the challenges women face in ensuring they have healthy concentrations of these carotenoids in the eye will lead to more comprehensive nutritional recommendations for the aging female population.
“Carotenoid deposition and metabolism are changed by a variety of factors, with sex being one of them,” Hammond noted. “The brain has an enormous metabolism, and most Americans don’t get more than one or two milligrams per day of lutein or zeaxanthin […] further, carotenoids are also deposited in fat, and their fat deposition is much greater in females than males which could be the root of some of the differences we see in morbidities.”
“A plethora of evidence exists that lutein and zeaxanthin have effects in the brain and target a lot of the morbidities we see in women, including macular degeneration and dementia,” Hammond continued. “A very recent study out of Harvard School of Medicine found that in almost 1,000 patients with dementia who were followed over a span of seven years, those with the highest intakes of the two carotenoids had over a 40% reduced chance of developing Alzheimer’s disease. About half of that sample died during the time it took to do the study, so they did brain histology and found a direct correlation between lutein and zeaxanthin and a lack of biomarkers of Alzheimer’s disease.”
Precision Nutrition
Howard Sesso, SCD, MPH, associate professor of medicine at Brigham and Women’s Hospital, discussed overall shortcomings when it comes to the most mainstream, large-scale nutritional research, in terms of the way researchers extrapolate benefits from men to women and vice-versa, and a lack of proper subgroup separation that comes with meta-analyses which makes it difficult to establish precision nutrition recommendations.
“We need to think more carefully about the role of sex when it comes to interpretations of clinical trials. The notion of how sex can factor into results has unfortunately been lost in nutritional research,” Sesso said, noting that trials he worked on such as the Physician’s Health Studies I and II and the Women’s Health Study, while well-conducted, lack the design for precise gender-specific recommendations.
“Limiting results to just men or just women diminishes the value of subgroup analyses by sex, age, race, or ethnicity,” Sesso noted. “We don’t need to start looking at 50 different subgroups, though, as that would lose the advantages of trial size.”
Trials that include only men or only women, while providing interesting findings, cause a need to reverse-engineer trial designs for the opposite sex, Sesso noted. “Why not include the other sex in the first place? It’s going to be a problem for dietary supplement research moving forward, and for leading researchers such as myself. We’ve seen incredibly interesting findings in studies such as the Women’s Antioxidant Cardiovascular Study, but the results fell quiet and weren’t followed up upon because they didn’t involve men, or people of a broader age range.”
Failing to account for differences in outcomes across sexes, and the health needs one can extrapolate from such data, have plagued meta-analyses and large-scale trials on multivitamins to date, Sesso noted, along with some specific trials on nutrients which have less-than-profound but important health benefits in certain populations.
As important as physiological differences are, so are average baseline nutritional statuses of men vs. women, Sesso noted. “This is a very under-appreciated factor in contemporary research. It’s not a matter of giving someone a supplement, it matters who receives that supplement and why. This will inform our understandings of personalized versus precision nutrition. Where personalized nutrition is based on genomic factors, things you can’t change, precision nutrition will take into account things you can change to improve over the long-term, such as the gut microbiome, metabolomics, genomics, proteomics, DNA methylation, and epigenetics. That’s how we’ll achieve a much better understanding of differences between women and men in nutrition, supplementation, and health.”
If You Missed Part 1 of Women's Health and Nutrition Research, Click Here ...
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at MMontemarano@RodmanMedia.com.
“Men and women even interpret what ‘sleep quality’ means differently,” Baker said. “Women are more likely to be morning types, and tend to have shorter circadian rhythms. They have more deep sleep and less light sleep, and feel less wakefulness after sleep onset than men do.”
Women are substantially more likely to experience insomnia, which is linked to hormonal changes, and comorbidities such as anxiety and depression, Baker noted. The reproductive cycle, especially post-menopause, is also a clear differentiating factor when it comes to risks of developing sleep disorders. While research is limited when it comes to the role that diet plays in sleep, aside from certain dietary supplement ingredients such as soy isoflavones, Baker said that delineating the differences between men and women—in terms of overall sleep quality, its perceptions, and sleep hygiene—will be key in uncovering new findings on the sleep front.
Disparities During Pregnancy
Regan Bailey, PhD, MPH, professor at Purdue University’s nutritional science department, discussed contemporary knowledge of the nutritional disparities women experience during pregnancy—a key target for future research crafting public health policy for the prevention of preeclampsia, gestational diabetes, adverse birth outcomes, unhealthy birth weight, and birth defects.
While the U.S. is ahead of the curve in some aspects, such as folic acid intake, maternal dietary supplementation on the whole falls short in key areas, such as iodine, Bailey said. Only one in five women takes a prenatal supplement containing iodine, despite daily requirements near-doubling upon the onset of pregnancy, in part for the prevention of problems with a child’s neurocognitive development. Likewise, the U.S. maternal population in the U.S. is only taking 2% of the recommended daily intake (RDI) of choline.
Meanwhile, many maternal supplements contain excessive amounts of nutrients that have upper limits in RDIs, Bailey added. NHANES data suggest that women in the U.S. are at risk for taking excessive amounts of folic acid, iron, and zinc. Further adding to this risk is the fact that many women who do take supplements already take in more vitamins and minerals through their diets alone than what are needed.
Further compounding the issue, “we know next to nothing about total usual dietary intakes of lactating women,” Bailey said.
Research on the ECHO (Environmental Influences on Child Health Outcomes) finds several disparities in its cohort of mothers when it comes to risks of insufficient nutrient intake. Age is the strongest link to nutrient intake during pregnancy, Bailey said, followed by racial background, with educational attainment also correlating to usage.
Diet and the Estrogen Balance
With estrogen levels in flux throughout a woman’s life cycle, nutrition research is revealing the role that diet—within a bigger picture of healthcare—can play in maintaining balanced estrogen levels, and what beneficial health outcomes could be tied to modulating the hormone, said Zeynep Madak-Erdogan, associate professor at the University of Illinois Urbana-Champaign.
Research on the topic has been especially prevalent when it comes to botanicals such as cranberry, soy isoflavones, licorice root, and more, with hypotheses that supplementation could improve symptoms linked to estrogen loss.
Estrogens work through a wide range of pathways to affect metabolism, reproductive function, bone health, and cancer risk. While hormone replacement therapy (HRT) is currently used for more serious medical applications, Madak-Erdogan said there’s a critical need to substantiate safer alternatives to HRT to deal with metabolic health consequences. Perhaps, she said, there is an interconnected role that botanicals could play in the reduction of breast cancer, cardiovascular, and obesity risk. Phytoestrogens have a noted impact on vasculature, the makeup and deposition of adipose tissue, and obesity, which is linked to significantly higher cancer risks. While more research is needed, botanicals may serve as alternatives to HRT without presenting risks to reproductive function.
The gut microbiome may be a key target, or at least a pathway, when it comes to natural therapies which can beneficially modulate estrogen levels, Madak-Erdogan said. “Estrogens are metabolized by bacteria, and bacteria are responsible for changing the half-life of estrogens in the body,” she said, noting that changes can be so significant that pregnancies have been attributed to antibiotics changing the gut microbiome enough to interfere with oral contraceptives. Still, “we don’t know the impact of dietary estrogens on the gut microbiome, or whether changes in bacteria can impact cancer or metabolic disease outcomes,” Madak-Erdogan said.
Women’s Eye and Brain Health
Women are uniquely affected by eye health issues, and how the eye ages has been shown to have an impact on cognitive aging, according to Billy Hammond, PhD, professor in the behavioral and brain sciences program at University of Georgia.
“From a prevalence perspective, about two-thirds of macular degeneration occurs in women. Dementia is also much more prevalent in women, and there are two different tracks for how both the eye and the brain age between men and women,” Hammond said. “The age-standardized rates for cataracts, in which things in the eyes oxidize and become opaque, significantly are higher in women globally.”
As a researcher with decades of background in the carotenoids lutein and zeaxanthin, Hammond said there are significant differences in the way that men and women metabolize them.
This is especially important to reproductive health applications, Hammond said, pointing to research which monitored maternal lutein and zeaxanthin intakes and linked them to improvements in cognitive behavioral indices in children during follow-up periods lasting several years. This furthers the case that visual acuity is directly tied to cognitive performance. “Lutein levels have been shown to extend vision up to 30%,” Hammond said. “Clearing up visual signals is also known to increase the processing of those signals. Taking care of hearing and vision is shown to slow cognitive decline, and we know this because hearing aids and cataract surgeries are linked to improvements in cognition.”
With those in the highest quintiles of retinal lutein and zeaxanthin experiencing a 24% lower risk of cognitive impairment, factoring in the challenges women face in ensuring they have healthy concentrations of these carotenoids in the eye will lead to more comprehensive nutritional recommendations for the aging female population.
“Carotenoid deposition and metabolism are changed by a variety of factors, with sex being one of them,” Hammond noted. “The brain has an enormous metabolism, and most Americans don’t get more than one or two milligrams per day of lutein or zeaxanthin […] further, carotenoids are also deposited in fat, and their fat deposition is much greater in females than males which could be the root of some of the differences we see in morbidities.”
“A plethora of evidence exists that lutein and zeaxanthin have effects in the brain and target a lot of the morbidities we see in women, including macular degeneration and dementia,” Hammond continued. “A very recent study out of Harvard School of Medicine found that in almost 1,000 patients with dementia who were followed over a span of seven years, those with the highest intakes of the two carotenoids had over a 40% reduced chance of developing Alzheimer’s disease. About half of that sample died during the time it took to do the study, so they did brain histology and found a direct correlation between lutein and zeaxanthin and a lack of biomarkers of Alzheimer’s disease.”
Precision Nutrition
Howard Sesso, SCD, MPH, associate professor of medicine at Brigham and Women’s Hospital, discussed overall shortcomings when it comes to the most mainstream, large-scale nutritional research, in terms of the way researchers extrapolate benefits from men to women and vice-versa, and a lack of proper subgroup separation that comes with meta-analyses which makes it difficult to establish precision nutrition recommendations.
“We need to think more carefully about the role of sex when it comes to interpretations of clinical trials. The notion of how sex can factor into results has unfortunately been lost in nutritional research,” Sesso said, noting that trials he worked on such as the Physician’s Health Studies I and II and the Women’s Health Study, while well-conducted, lack the design for precise gender-specific recommendations.
“Limiting results to just men or just women diminishes the value of subgroup analyses by sex, age, race, or ethnicity,” Sesso noted. “We don’t need to start looking at 50 different subgroups, though, as that would lose the advantages of trial size.”
Trials that include only men or only women, while providing interesting findings, cause a need to reverse-engineer trial designs for the opposite sex, Sesso noted. “Why not include the other sex in the first place? It’s going to be a problem for dietary supplement research moving forward, and for leading researchers such as myself. We’ve seen incredibly interesting findings in studies such as the Women’s Antioxidant Cardiovascular Study, but the results fell quiet and weren’t followed up upon because they didn’t involve men, or people of a broader age range.”
Failing to account for differences in outcomes across sexes, and the health needs one can extrapolate from such data, have plagued meta-analyses and large-scale trials on multivitamins to date, Sesso noted, along with some specific trials on nutrients which have less-than-profound but important health benefits in certain populations.
As important as physiological differences are, so are average baseline nutritional statuses of men vs. women, Sesso noted. “This is a very under-appreciated factor in contemporary research. It’s not a matter of giving someone a supplement, it matters who receives that supplement and why. This will inform our understandings of personalized versus precision nutrition. Where personalized nutrition is based on genomic factors, things you can’t change, precision nutrition will take into account things you can change to improve over the long-term, such as the gut microbiome, metabolomics, genomics, proteomics, DNA methylation, and epigenetics. That’s how we’ll achieve a much better understanding of differences between women and men in nutrition, supplementation, and health.”
If You Missed Part 1 of Women's Health and Nutrition Research, Click Here ...
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at MMontemarano@RodmanMedia.com.
