Nutrition News May 8


  • Probiotic supplements containing Lactobacillus rhamnosus may reduce the risk of diabetes during pregnancy.
  • High choline intake is associated with greater bone mineral density, potentially reducing the risk of osteoporosis.
  • Human milk oligosaccharides have protective effects on the digestive system in infants, especially preterm infants.
  • NMN – Nicotinamide Mononucleotide  may help slow disease, according to study on sirtuins and brain NAD+

New Research From Around the World

Lots of recent papers came to our attention this week. Here are summaries of the most interesting or relevant studies, categorized by subject.

  1. Obesity and Weight Loss
  2. Blood Sugar Control and Diabetes
  3. Heart Health
  4. Cancer
  5. Appetite and Eating
  6. Digestive Health
  7. Liver Health
  8. Bone Health
  9. Longevity and Healthy Aging

1. Obesity and Weight Loss

Fruit Juice and Change in BMI: A Meta-analysis.

This meta-analysis of observational studies concluded that regularly drinking 100% fruit juice without added sugar is associated with a slightly increased risk of weight gain in children aged 1–6.

However, the authors considered the weight gain clinically insignificant. Also, no statistically significant association was found between 100% fruit juice intake and weight gain in children and adolescents aged 7–18.

2. Blood Sugar Control and Diabetes

Higher Maternal Dietary Protein Intake Is Associated with a Higher Risk of Gestational Diabetes Mellitus in a Multiethnic Asian Cohort.

This observational study in 980 Asian women found that a higher intake of both animal and vegetable protein was associated with an increased risk of diabetes during pregnancy.

Association of maternal serum 25-hydroxyvitamin D concentrations in second and third trimester with risk of gestational diabetes and other pregnancy outcomes.

This observational study in 4,718 women showed that high circulating levels of vitamin D were associated with an increased risk of diabetes during pregnancy.

Women low in vitamin D were also at an increased risk of adverse pregnancy outcomes, such as stillbirth, miscarriage and anemia.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

This controlled study in pregnant women found that supplementing with the probiotic Lactobacillus rhamnosus early in pregnancy may reduce the risk of diabetes during pregnancy by 69%.

However, this was only statistically significant in women aged 35 or older or those who had previously suffered from diabetes during pregnancy.

3. Heart Health

Effects of Two Different Dietary Patterns on Inflammatory Markers, Advanced Glycation End Products and Lipids in Subjects without Type 2 Diabetes: A Randomised Crossover Study.

This crossover study in 51 adults compared the effects of two, four-week diets: 1) a diet high in red, processed meat and refined grains (HMD), and 2) a diet high in dairy, whole grains, nuts and legumes (HWD).

The study showed that levels of plasminogen activator inhibitor-1 (PAI-1), which is a risk factor for heart disease and blood clots, were higher after the HMD. No significant differences in inflammatory markers or blood lipids were detected.

Dietary inflammatory index and risk of first myocardial infarction; a prospective population-based study.

The Dietary Inflammatory Index (DII) rates the inflammatory potential of a diet. Some foods may be pro-inflammatory, whereas others may be anti-inflammatory.

This observational study in 6,944 Swedish adults showed that a pro-inflammatory diet increased the risk of having a first heart attack in males, whereas no significant links were found in women.

4. Cancer

Supplemental Selenium May Decrease Ovarian Cancer Risk in African-American Women.

This observational study in 1,038 African-American women showed that those who supplemented with the highest amounts of selenium were at a 30% lower risk of ovarian cancer, compared to those who didn’t supplement.

However, there was no significant association between the intake of selenium from food and ovarian cancer.

Prediagnostic enterolactone concentrations and mortality among Danish men diagnosed with prostate cancer.

Enterolactone is a lignan produced by intestinal bacteria from other dietary lignans. Lignans are antioxidant polyphenols that are abundant in some high-fiber foods, such as whole grains, fruits and vegetables.

This observational study in 1,390 Danish men who were diagnosed with prostate cancer found no significant association between circulating enterolactone levels (measured before diagnosis) and the risk of death during follow-up.

Fruit and vegetable intake and breast cancer prognosis: a meta-analysis of prospective cohort studies.

This meta-analysis of observational studies, including a total of 41,185 women, found no significant links between the intake of fruits and vegetables and the risk of breast cancer.

5. Appetite and Eating

Hunger and satiety responses to high-fat meals after a high polyunsaturated fat diet: A Randomized Trial.

Previous single-meal studies indicate that polyunsaturated fats (PUFAs) cause a greater satiety than other types of fat. However, the long-term effects of high-PUFA diets have not been examined.

This seven-day study in 26 adults showed that a high-PUFA diet increased fasting and post-meal levels of peptide YY (PYY), which is a marker of satiety, compared to the control diet. However, the participants didn’t report any changes in their appetite.

Color of hot soup modulates postprandial satiety, thermal sensation, and body temperature in young women.

This study in 12 young women found that eating a blue potato soup significantly reduced willingness to eat and ratings of palatability, comfort, warmth and anxiety, compared to soups that were white or yellow but otherwise identical.

Additionally, self-reported satiety was lower after eating the blue soup.

6. Digestive Health

Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants.

Necrotising enterocolitis (NE) is one of the most common intestinal disorders in preterm infants. The risk of death among infants with NE is quite high. Breastfed infants are at a significantly lower risk of NE than those who are formula fed.

This observational study in 200 mothers and their infants showed that the levels of disialyllacto-N-tetraose, a type of human milk oligosaccharide, were significantly lower in the breast milk of mothers whose children developed NE.

7. Liver Health

Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort.

Oxidative stress is when levels of oxidants are high relative to levels of antioxidants. Over time, oxidative stress may cause damage to the body and increase the risk of chronic disease.

This observational study in 487 HIV-infected people, some of which had hepatitis C (liver inflammation), found that low zinc levels were associated with increased oxidative stress and liver fibrosis, which is one of the symptoms of hepatitis.

8. Bone Health

Dietary Choline Intake Is Directly Associated with Bone Mineral Density in the Hordaland Health Study.

Choline is a nutrient mainly found in animal-sourced foods, such as eggs and liver, but small amounts are also found in plants. Dietary intake of choline is not essential since the body can generally produce sufficient amounts.

This observational study in 4,632 middle-aged and older adults showed that a high dietary choline intake was associated with higher bone mineral density, possibly reducing the risk of osteoporosis.

Dairy Intake Is Protective against Bone Loss in Older Vitamin D Supplement Users: The Framingham Study.

Bone mineral density (BMD) is the amount of minerals, such as calcium, found in your bones. It tends to decrease with age. Low BMD is associated with an increased risk of osteoporosis and fractures.

This observational study in older Caucasian adults found that a higher intake of dairy, milk, yogurt and cheese was associated with greater BMD. Taking vitamin D supplements seemed to increase this protective effect of dairy.

9. Longevity and Healthy Aging

Serum 25-Hydroxyvitamin D Has a Modest Positive Association with Leukocyte Telomere Length in Middle-Aged US Adults.

Telomeres are sequences of DNA at the ends of DNA strands, which protect them from fusing with neighboring strands. They naturally shorten with age, but oxidative stress may accelerate their shortening, possibly contributing to aging.

This observational study showed that low vitamin D levels were modestly associated with a shorter telomere length in the white blood cells of middle-aged US adults.

Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with All-Cause and Cause-Specific Mortality in Adults.

This observational study found that following Mediterranean or Paleolithic dietary patterns was associated with a reduced risk of death from any cause.

Specifically, those who followed diets who most resembled the Mediterranean or Paleolithic diets were at a 23% reduced risk of death during the study’s six-year average follow-up.

Postdiagnostic Mediterranean and Healthy Nordic Dietary Patterns Are Inversely Associated with All-Cause Mortality in Long-Term Colorectal Cancer Survivors.

This observational study in colorectal cancer survivors found that following a Mediterranean (MD) or Nordic dietary pattern (ND) was linked to a lower risk of death from any cause during the six years of follow-up.

Specifically, those who adhered most to the MD were at a 52% lower risk of dying during the follow-up period, while closely following the ND was linked to a 37% lower risk.

Intake of Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Mortality in Renal Transplant Recipients.

Intake of long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is linked to various health benefits.

This observational study in 627 kidney transplant recipients showed that a high intake of EPA and DHA was associated with a lower risk of death from any cause, especially in older and non-smoking individuals.

Circulating eNAMPT and NAD+ is reduced during ageing

This review is published here:

It will be of great interest to examine whether the activity of circulating eNAMPT is reduced during ageing. eNAMPT also affects other brain regions, and it has been reported that eNAMPT conveys neuroprotection against ischae-mia-induced or ischaemia–reperfusion-induced neuronal injuries.Given that NAMPT produces NMN from nicotinamide and 5-phosphoribosyl-pyrophosphate, NMN itself might have some important functions as a circulating signalling molecule.

Indeed, it has been reported that plasma levels of NMN decrease with age, and administration of NMN to aged mice ameliorates age-associated reduction in glucose-stimulated insulin secretion136, skeletal muscle mito-chondrial function, NSC pool and arterial function.

It has recently been demonstrated that long-term admin-istration of NMN mitigates age-associated physiological decline in mice(139). NMN also ameliorates disease condi-tions, including type2 diabetes induced by high-fat diet or age(140), brain damage in a cerebral ischaemia–reperfusion mouse model, and cognitive impairment and amyloid deposition in Alzheimer disease model rodents.

In addition, administration of nicotinamide riboside (NR), which is phosphorylated by nicotinamide riboside kinases to yield NMN, improves oxidative metabolism in skeletal muscle and brown adipose tissue, attenuates cognitive deterioration in an Alzheimer disease mouse model and induces activation of the mitochondrial unfolded protein response and synthesis of prohibitin proteins in mitochondria, rejuvenating muscle adult stem cells in aged mice(146).

Therefore, it is likely that these NAD+ intermediates play a critical part in the regulation of mammalian ageing and longevity, potentially through their effects on NAD+ biosynthesis and sirtuin activity in the hypothalamus and other key tissues andorgans.Other circulating factors.

Over the past 10years, stud-ies using parabiosis have accelerated the identification of circulating factors that influence tissue ageing .

Circulating hormones or factors transferred from young to old individuals (het-erochronic parabiosis) ameliorate age-associated dys-functions in the brain such as adult neurogenesis(148,149) cognition(148,149) regeneration(150) and angiogenesis.

In addition, young monocytes and/or macrophages facil-itate differentiation of oligodendrocyte precursor cells and remyelination by augmenting the clearance of inhib-itory myelin debris in the injured brain(150). By contrast, circulatory factors that rise with ageing can impair the young brain.

For example, plasma levels of chemokine C-C motif chemokine11 (CCL11; also known as eotaxin) rise with age in mice and humans. Systemic injection of CCL11 impairs adult neurogenesis and cognitive func-tion in young mice(148).

Similarly, blood levels of β2-mi-croglobulin are elevated in ageing mice and humans, and systemic injection or local injection of this molecule into the hippocampus impairs hippocampal-dependent cog-nitive function and neurogenesis in young mice(149).

The implication from such parabiosis studies is that brain ageing could be modifiable by targeting factors from the periphery in addition to targeting factors within thebrain

.Several factors secreted from peripheral tissues have been identified that are candidates to ameliorate age-associated pathophysiologies in the brain. Fibroblast growth factor21 (FGF21) is known as a hepatokine, myokine and adipokine(151).

Overexpression of FGF21 in mice promotes lifespan extension(152), possibly via reduced activity of the insulin– insulin-like growth fac-tor1 (IGF1) signaling pathwa3. The central effects of FGF21 are mediated through a receptor complex con-sisting of the FGF receptor and its co-receptor β-klotho, a transmembrane protein expressed in the brain(154156).

Overexpression of FGF21 suppresses wheel-running activity(156) and terminates the oestrous cycles by sup-pressing the vasopressin–kisspeptin signalling cascade in the SCN, thereby inhibiting the pro-oestrus surge of lutenizing hormone(155).

Moreover, in a model of ageing involving chronic -galactose administration, which causes neuronal damage by inducing oxidative stress, sys-temic administration of FGF21 protects the brain from injury by attenuating oxidative stress damage and decreas-ing advanced glycation end products157.

These results sug-gest that circulating FGF21 protects SCN neurons — and the brain generally — against age-associated pathophysi-ological changes during ageing(152).

Growth differentiation factor11 (GDF11), a secreted growth factor from mature neurons, was found to be present in the blood from young mice and could act as a rejuvenating factor for the brains of aged animals158.

Indeed, daily injection of GDF11 enhances vascular remodelling and neurogenesis in old (22month) mice158. Other reports confirmed these ini-tial results, although they showed that the reagents used to detect GDF11 also detected a related protein, GDF8 (REFS159,160).

We look forward to additional studies to further clarify the role of GDF11 inageing.Growing evidence suggests that myokines may also modulate the process of ageing at a systemic level.

Indeed, in skeletal muscle, reduced mTOR complex1 (mTORC1) signalling resulted in enhanced activity of eukaryotic translation initiation factor 4E-binding pro-tein1 (4EBP1, a key downstream effector of mTORC1), which in turn increased FGF21 secretion and mediated the protection against age-induced and diet-induced insulin resistance and metabolic rate decline through-out the body161. IL-6 is a cytokine produced by immune cells, vascular endothelial cells, adipocytes and skeletal muscle.

A significant amount of IL-6 is produced and released from skeletal muscle after exercise162. IL-6 can cross the BBB163 via saturable transporter systems163, and, in the elderly, elevated levels are linked to poor cognitive function, higher risk of age-associated dis-eases, physical disability and higher mortality164.

Finally, it has recently been reported that, in mice, intravenous injection of the presumed hormone fibronectin typeIII domain-containing protein5 (FNDC5), the precursor of irisin, leads to a significant increase in Bdnf expres-sion in the hippocampus165.

However, direct application of irisin to cultured hippocampal neurons does not increase Bdnf expression, suggesting that FNDC5 might have another cleavage product (other than irisin) that can induce Bdnf expression166.Other candidates.

The identification of circulating mol-ecules that have an impact on brain function and its ageing would be not only a clinically useful biomarker of ageing but also a putative preventive and therapeu-tic target for age-associated dysfunctions and diseases. Other promising circulating factors include circulating microRNAs and endothelial progenitor cells, the levels of which decline with age167–171.

Further investigation on these circulating molecules will enrich our knowledge on the inter-tissue communications between the brain and peripheral tissues and organs in the systemic regulation of ageing and longevity in mammals.

Future directionsOver the past 20years, there has been tremendous pro-gress in understanding the mechanisms of ageing and longevity.

Nonetheless, the complexity of ageing as a bio-logical phenomenon is still a big challenge. An emerg-ing approach to understand the tremendous biological complexity of the ageing process at any level of physi-ological hierarchy is to systematically analyse a wealth of ‘omics’ data, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, and clin-ical data from different clinical trials throughout the world172–174.

Such a big data-driven integrative approach will help to identify crucial brain pathways that govern mammalian ageing.

We hope to address the following important questions to better understand the systemic regulation of mammalian ageing and longevity: what are the primary mechanisms that deteriorate in brain func-tion to affect the ageing process?

What are the crucial feedback loops between the brain and peripheral tissues that govern ageing? What therapeutic interventions can counteract the effects of ageing on these feedback loops? A perspective that considers the brain at the centre of ageing seems to be warranted and may speed progress in answering these questions.