Guylaine Ferland

Dietary induced subclinical vitamin K deficiency in normal human subjects

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.

Relationship of plasma carotenoids, retinol and tocopherols in mothers and newborn infants

OBJECTIVE We studied the relationship between maternal and cord plasma concentrations of carotenoids, retinol, and tocopherols in normal mother-baby pairs. METHODS Healthy pregnant women (n = 10) were recruited at a Montréal hospital. Venous blood samples were collected from the mothers at delivery and cord blood was obtained immediately post partum from the umbilical vein after clamping of the cord. All deliveries were full term deliveries and all babies had normal birth weights. Maternal and umbilical cord blood samples were handled identically. Plasma was digested with lipase and plasma carotenoids were extracted and measured using HPLC. RESULTS Cord plasma concentration of carotenoids were significantly lower than that of maternal plasma (p < 0.001). There was a high correlation of lutein (r = 0.889, p = 0.006) and cryptoxanthin (r = 0.912, p = 0.0002) between maternal plasma concentrations and cord plasma concentrations. The concentrations of the hydrocarbon carotenoids, alpha-carotene and beta-carotene, were also correlated (r = 0.779, p = 0.0133, & r = 0.782, p = 0.0076, respectively) between maternal plasma and cord plasma. Whereas the plasma concentration of the acyclic carotenoid, lycopene, showed no correlation between the two groups, after adjustment for plasma triglycerides, the lycopene correlation between maternal and cord plasma was the highest (r = 0.975, p = 0.0001) of all the carotenoids tested. Cord plasma retinol concentration, which was 50% of that of maternal plasma, was also found to have no correlation with that of maternal plasma. Plasma concentration of alpha-tocopherol showed no correlation between two groups, whereas there was high correlation between cord and maternal gamma-tocopherol concentrations (r = 0.808, p = 0.0047). CONCLUSION The nutritional status of mothers affects the nutritional status of their babies for certain fat soluble nutrients.

Prevalence of Low Bone Mass and Deficiencies of Vitamins D and K in Pediatric Patients With Cystic Fibrosis From 3 Canadian Centers

OBJECTIVE. In this cross-sectional observational study, we assessed both vitamins D and K status and bone health in pancreatic insufficient pediatric patients with cystic fibrosis from 3 Canadian cystic fibrosis centers. METHODS. Eighty-one patients who had cystic fibrosis and were clinically stable for at least 3 months were enrolled. At the time of the clinic visit, anthropometric variables, lung function, pubertal status, intake of calcium and vitamins D and K, and physical activity were assessed. Blood was taken for analysis of biochemical biomarkers of bone turnover and status of vitamins D and K, and a urine sample was obtained for calcium, creatinine, sodium, and deoxypyridoline analyses. Whole-body bone mineral content and lumbar spine (L1–L4) bone mineral density were measured. RESULTS. The children were relatively well nourished and had moderate to mild lung disease. Low bone mineral mass defined as a z score between −1.0 and −2.0, for gender and age was detected in 38% of the children for whole body and in 28% for lumbar spine. z score less than −2.0 was observed in 7 children for both bone measures. Suboptimal vitamin D status occurred in 95% of patients; suboptimal vitamin K status occurred in 82% of patients. Measures of plasma osteocalcin and carboxy-terminal propeptide type 1 procollagen and urinary deoxypyridoline compared with reference values for age, gender, and pubertal status reflected a state of suppressed bone formation and elevated bone resorption in a large proportion of the patients. CONCLUSIONS. Bone mass of the whole body and spine was lower than expected for chronological age in approximately one third of pediatric patients with cystic fibrosis irrespective of gender or age. This may be explained by the observation of low bone turnover for developmental stage as indicated by bone biomarkers. Suboptimal status of vitamins D and K may be key causative factors of the low bone status for age.

Vitamin K and the Nervous System: An Overview of its Actions

The role of vitamin K in the nervous system has been somewhat neglected compared with other physiological systems despite the fact that this nutrient was identified some 40 y ago as essential for the synthesis of sphingolipids. Present in high concentrations in brain cell membranes, sphingolipids are now known to possess important cell signaling functions in addition to their structural role. In the past 20 y, additional support for vitamin K functions in the nervous system has come from the discovery and characterization of vitamin K-dependent proteins that are now known to play key roles in the central and peripheral nervous systems. Notably, protein Gas6 has been shown to be actively involved in cell survival, chemotaxis, mitogenesis, and cell growth of neurons and glial cells. Although limited in number, studies focusing on the relationship between vitamin K nutritional status and behavior and cognition have also become available, pointing to diet and certain drug treatments (i.e., warfarin derivatives) as potential modulators of the action of vitamin K in the nervous system. This review presents an overview of the research that first identified vitamin K as an important nutrient for the nervous system and summarizes recent findings that support this notion.

Development and validation of a food frequency questionnaire.

Regular diet monitoring requires a tool validated in the target population. A 73-item, semiquantitative, self-administered food frequency questionnaire (FFQ), was adapted in French and English from the Block National Cancer Institute Health Habits and History Questionnaire. The FFQ was used to capture usual long-term food consumption among adults living in Quebec. A representative sample of adults aged 18 to 82 (57% female) was recruited by random digit dialling in the Montreal region. Approximately 64% of recruits completed and returned the instrument by mail (n=248). The FFQ was validated in a subsample (n=94, 61% female) using four nonconsecutive food records (FRs). Median energy intakes (in kcal) for men and women, respectively, were FFQ (total sample) 2,112 and 1,823, FFQ (subsample) 2,137 and 1,752, and FR (subsample) 2,510 and 1,830. Spearman correlation analyses between FFQ and FR nutrients were positive (with r ranging from 0.32 for folate to 0.58 for saturated fatty acids) and statistically significant (p<0.001), with better results among women. On average, cross-classification of energy and 24 nutrients from the FFQ and means of four FRs placed 39% into identical quartiles and 78% into identical and contiguous quartiles, with only 4% frankly misclassified. These results suggest that the FFQ is a relatively valid instrument for determining usual diet in Quebec adults.Regular diet monitoring requires a tool validated in the target population. A 73-item, semiquantitative, self-administered food frequency questionnaire (FFQ), was adapted in French and English from the Block National Cancer Institute Health Habits and History Questionnaire. The FFQ was used to capture usual long-term food consumption among adults living in Quebec. A representative sample of adults aged 18 to 82 (57% female) was recruited by random digit dialling in the Montreal region. Approximately 64% of recruits completed and returned the instrument by mail (n=248). The FFQ was validated in a subsample (n=94, 61% female) using four nonconsecutive food records (FRs). Median energy intakes (in kcal) for men and women, respectively, were FFQ (total sample) 2,112 and 1,823, FFQ (subsample) 2,137 and 1,752, and FR (subsample) 2,510 and 1,830. Spearman correlation analyses between FFQ and FR nutrients were positive (with r ranging from 0.32 for folate to 0.58 for saturated fatty acids) and statistically sign...Regular diet monitoring requires a tool validated in the target population. A 73-item, semiquantitative, self-administered food frequency questionnaire (FFQ), was adapted in French and English from the Block National Cancer Institute Health Habits and History Questionnaire. The FFQ was used to capture usual long-term food consumption among adults living in Quebec. A representative sample of adults aged 18 to 82 (57% female) was recruited by random digit dialling in the Montreal region. Approximately 64% of recruits completed and returned the instrument by mail (n=248). The FFQ was validated in a subsample (n=94, 61% female) using four nonconsecutive food records (FRs). Median energy intakes (in kcal) for men and women, respectively, were FFQ (total sample) 2,112 and 1,823, FFQ (subsample) 2,137 and 1,752, and FR (subsample) 2,510 and 1,830. Spearman correlation analyses between FFQ and FR nutrients were positive (with r ranging from 0.32 for folate to 0.58 for saturated fatty acids) and statistically sign...

Low Vitamin K Intakes in Community-Dwelling Elders at an Early Stage of Alzheimer's Disease

An increasing body of evidence points to a role for vitamin K in brain physiology through its participation in sphingolipid metabolism and biological activation of the vitamin K-dependent protein Gas6. One hypothesis is that vitamin K may also play a role in the pathogenesis of Alzheimers disease. A recent study found that patients with early-stage Alzheimers disease consumed less vitamin K than did cognitively intact control subjects. To learn more about the dietary intakes and food sources of vitamin K in these patients, a detailed analysis was conducted. Dietary vitamin K intakes were assessed from 5 nonconsecutive days of food records collected from 31 community-dwelling patients with early-stage Alzheimers disease and in 31 age- and sex-matched cognitively intact control subjects. Mean vitamin K intake on a person-day basis was 63+/-90 microg/day in patients and 139+/-233 microg/day in control subjects. Vitamin K intakes were significantly less in participants with Alzheimers disease (P<0.0001), even after adjusting for energy intakes (P=0.0003). Vegetables, fats, and fruits contributed more than 70% of total vitamin K intake in both groups. The main source of vitamin K was green vegetables, which contributed 33% and 49% to total intakes in patients and control subjects, respectively. This lower consumption of green vegetables in participants with Alzheimers disease explained their lower vitamin K intakes overall. Despite their limitations, results are in line with the most recent research in both vitamin K and Alzheimers disease and suggest a need to consider vitamin K in future investigations on the role of diet in Alzheimers disease.

Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice.

Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR(-/-)hApoB(+/+); 3 mo old) mice with catechin (30 mg · kg(-1) · day(-1)) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P < 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P < 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities.

Diet quality and cognition among older adults from the NuAge study.

BACKGROUND AND OBJECTIVES A healthy diet may prevent cognitive decline either directly, or by decreasing risk of nutrition-related chronic diseases associated with cognitive decline. This study examined the relationships between diet quality (DQ) and cognition for over 3 years among 1488 older adults (52.6% female) from the NuAge study, aged 67 to 84 years at recruitment. METHODS Cognition was assessed at four annual visits using the modified mini-mental status examination (3MS); rate of cognitive decline was computed for each participant over the 3 years of follow-up using mixed model analyses and the individual-specific number of months between 3MS assessments. Dietary data were collected at recruitment using a validated 78-item, semi-quantitative food frequency questionnaire (FFQ). DQ was characterized as the Canadian Healthy Eating Index (C-HEI), a 9-component global DQ index (maximum score=100) computed from the FFQ output. Other variables were collected by questionnaire or direct measurement. Multivariate analyses were carried out to assess the association of DQ controlled for confounders on cognition. RESULTS Total C-HEI was better in females (78.7±9.1 vs 75.7±9.4, p<.0001) as were C-HEI component subscores. Males, the less educated, smokers, those with poor social engagement, symptoms of depression, a higher waist:hip ratio and who reported financial insecurity had a poor quality diet that could contribute to chronic diseases associated with cognition. Along with functional autonomy, most of these variables emerged as covariates of baseline 3MS and predictors of cognitive decline. While certain C-HEI subscores and total C-HEI were positive univariate correlates of 3MS at recruitment, total DQ was not associated with cognition in multivariate analyses, either at baseline or over 3 years of follow-up. CONCLUSIONS DQ was not independently associated with cognition. However, the study demonstrates relationships between diet quality and risk factors for chronic diseases associated with cognition. Consequently, older adults might benefit from a healthy diet to decrease risk of nutrition-related chronic diseases established as risk factors for cognitive decline. Further work in diverse older populations, use of dietary data collected earlier in life, finer cognitive measures and longer follow-up are necessary to better elucidate relationships between diet quality, chronic diseases and cognition.

Vitamin K, an emerging nutrient in brain function

Historically discovered for its role in blood coagulation, there is now convincing evidence that vitamin K has important actions in the nervous system. As a unique cofactor to the γ‐glutamyl carboxylase enzyme, vitamin K contributes to the biological activation of proteins Gas6 and protein S, ligands for the receptor tyrosine kinases of the TAM family (Tyro3, Axl, and Mer). Functionally, Gas6 has been involved in a wide range of cellular processes that include cell growth, survival, and apoptosis. In brain, vitamin K also participates in the synthesis of sphingolipids, an important class of lipids present in high concentrations in brain cell membranes. In addition to their structural role, sphingolipids are now known to partake in important cellular events such as proliferation, differentiation, senescence and cell–cell interactions. In recent years, studies have linked alterations in sphingolipid metabolism to age‐related cognitive decline and neurodegenerative diseases such as Alzheimers disease (AD). Emerging data also point to unique actions of the K vitamer menaquinone‐4 (MK‐4) against oxidative stress and inflammation. Finally, there is now data to suggest that vitamin K has the potential to influence psychomotor behavior and cognition. This review presents an overview of what is known of the role of vitamin K in brain function.

Sodium intake and physical activity impact cognitive maintenance in older adults: the NuAge Study.

This study examines the association between sodium intake and its interaction with physical activity on cognitive function over 3 years in older adults residing in Québec, Canada. We analyzed a subgroup from the NuAge cohort (aged 67-84 years) with nutrient intake data, including sodium, from a food frequency questionnaire administered at baseline. Baseline physical activity was assessed using the Physical Activity Scale for the Elderly (PASE; high-low). Modified Mini Mental State Examination (3MS) was administered at baseline and annually for 3 additional years. Controlling for age, sex, education, waist circumference, diabetes, and dietary intakes, analyses showed an association between sodium intake and cognitive change over time in the low PASE group only. Specifically, in the low PASE group, elders in the low sodium intake tertile displayed better cognitive performance over time (mean decline in 3MS over years: mean [M] = -0.57, standard error [SE] = 0.002) compared with the highest (M = -1.72, SE = 0.01) and mid sodium intake (M = -2.07, SE = 0.01) groups. This finding may have significant public health implications, emphasizing the importance of addressing multiple lifestyle factors rather than a single domain effect on brain health.