Mothers' Breast Milk Composition and Their Respective Infant's Gut Microbiota Differ between Five Distinct Rural and Urban Regions in Vietnam.

Microbiota colonization and development in early life is impacted by various host intrinsic (genetic) factors, but also diet, lifestyle, as well as environmental and residential factors upon and after birth. To characterize the impact of maternal nutrition and environmental factors on vaginally born infant gut microbiota composition, we performed an observational study in five distinct geographical areas in Vietnam. Fecal samples of infants (around 39 days old) and fecal and breast milk samples of their mothers (around 28 years) were collected. The microbiota composition of all samples was analyzed by 16S rRNA gene Illumina sequencing and a bioinformatics workflow based on QIIME. In addition, various breast milk components were determined. Strong associations between the geographically determined maternal diet and breast milk composition as well as infant fecal microbiota were revealed. Most notable was the association of urban Ha Noi with relatively high abundances of taxa considered pathobionts, such as Klebsiella and Citrobacter, at the expense of Bifidobacterium. Breast milk composition was most distinct in rural Ha Long Bay, characterized by higher concentrations of, e.g., docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), selenium, and vitamin B12, while it was characterized by, e.g., iron, zinc, and α-linolenic acid (ALA) in Ha Noi. Breast milk iron levels were positively associated with infant fecal Klebsiella and negatively with Bifidobacterium, while the EPA and DHA levels were positively associated with Bifidobacterium. In conclusion, differences between five regions in Vietnam with respect to both maternal breast milk and infant gut microbiota composition were revealed, most likely in part due to maternal nutrition. Thus, there could be opportunities to beneficially steer infant microbiota development in a more desired (rural instead of urban) direction through the mother's diet.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination. Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) µg/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3. We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce selenoprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials.

Thyroidal and Extrathyroidal Requirements for Iodine and Selenium: A Combined Evolutionary and (Patho)Physiological Approach.

Iodide is an antioxidant, oxidant and thyroid hormone constituent. Selenoproteins are needed for triiodothyronine synthesis, its deactivation and iodine release. They also protect thyroidal and extrathyroidal tissues from hydrogen peroxide used in the 'peroxidase partner system'. This system produces thyroid hormone and reactive iodine in exocrine glands to kill microbes. Exocrine glands recycle iodine and with high urinary clearance require constant dietary supply, unlike the thyroid. Disbalanced iodine-selenium explains relations between thyroid autoimmune disease (TAD) and cancer of thyroid and exocrine organs, notably stomach, breast, and prostate. Seafood is iodine unconstrained, but selenium constrained. Terrestrial food contains little iodine while selenium ranges from highly deficient to highly toxic. Iodine vs. TAD is U-shaped, but only low selenium relates to TAD. Oxidative stress from low selenium, and infection from disbalanced iodine-selenium, may generate cancer of thyroid and exocrine glands. Traditional Japanese diet resembles our ancient seashore-based diet and relates to aforementioned diseases. Adequate iodine might be in the milligram range but is toxic at low selenium. Optimal selenoprotein-P at 105 µg selenium/day agrees with Japanese intakes. Selenium upper limit may remain at 300-400 µg/day. Seafood combines iodine, selenium and other critical nutrients. It brings us back to the seashore diet that made us what we currently still are.

Pregnant Dutch Women Have Inadequate Iodine Status and Selenium Intake.

Iodine and selenium are essential for thyroid hormone synthesis. Iodine and selenium interact. Pregnancy increases the maternal iodine requirement. We previously reported inadequate iodine status in pregnant Dutch women. Since little is known about their selenium intake, we investigated the iodine status and selenium intake in relation to iodine and selenium supplement use during pregnancy. Iodine status was established in 201 apparently healthy pregnant women as 24 h iodine excretion (24H-UIE; sufficient if median ≥225 µg), iodine concentration (24H-UIC; ≥150 µg/L) and iodine/creatinine ratio (24H-UICR; ≥150 µg/g). Selenium intake was calculated from 24 h selenium excretion. Iodine status in pregnancy proved insufficient (medians: 24H-UIE 185 µg; 24H-UIC 95 µg/L; 24H-UICR 141 µg/g). Only women taking 150 µg iodine/day were sufficient (median 24H-UIE 244 µg). Selenium intake was below the Estimated Average Requirement (EAR; 49 µg/day) in 53.8%, below the Recommended Dietary Allowance (RDA; 60 µg/day) in 77.4% and below the Adequate Intake (AI; 70 µg/day) in 88.7%. Combined inadequate iodine status and selenium intake

Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.

Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2-6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64-0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35-0.82), 0.48 (0.30-0.75), and 0.51 (0.33-0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

C-reactive protein in traditional melanesians on Kitava.

BACKGROUND: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. METHODS: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). RESULTS: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1-48 mg/L and Mdn 1.1 mg/L range 0.1-33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. CONCLUSIONS: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.

Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality in the general population: results from the prospective Lifelines-MINUTHE study.

BACKGROUND: Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels are associated with mortality if vitamin B12 and eGFR are taken into account. METHODS: A total of 1533 individuals (aged 60-75 years, 50% male) were included from the Lifelines Cohort and Biobank Study. Individuals were included between 2006 and 2013, and the total follow-up time was 8.5 years. RESULTS: Median [IQR] age of the study population was 65 [62-69] years, 50% was male. At baseline, median MMA concentration was 170 [138-216] nmol/L, vitamin B12 290 [224-362] pmol/L, and eGFR 84 [74-91] mL/min/1.73 m2. Log2 vitamin B12, log2 eGFR, age, and sex were significantly associated with log2 MMA in multivariable linear regression analyses (model R2 = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log2 MMA levels were significantly associated with mortality (hazard ratio [HR] 1.67 [95% CI 1.25-2.22], P < 0.001). Moreover, we found a significant interaction between MMA and eGFR with respect to mortality (Pinteraction < 0.001). CONCLUSIONS: Only 22% of variation in MMA levels was explained by vitamin B12, eGFR, age, and sex, indicating that a large part of variation in MMA levels is attributable to other factors (e.g., catabolism, dietary components, or gut microbial production). Higher MMA levels are associated with an increased risk for mortality, independent of vitamin B12, eGFR, and sex. This association was more pronounced in individuals with impaired renal function.

Temporal Changes in Breast Milk Fatty Acids Contents: A Case Study of Malay Breastfeeding Women.

The composition of human breast milk changes in the first two months of life, adapting itself to the evolving needs of the growing new-born. Lipids in milk are a source of energy, essential fatty acids (FA), fat-soluble vitamins, and vital bioactive components. Information on breast milk FA of Malaysian lactating women is scarce. Based on convenience sampling, a total of 20 Malay breastfeeding women who fulfilled the inclusion criteria were recruited. Breast milk was collected three times from each subject at consecutive intervals of 2-3 weeks apart. A total of 60 breast milk samples were collected and classified into "transitional milk" (n = 8), "early milk" (n = 26) and "mature milk" (n = 26). All milk samples were air freighted to University of Groningen, Netherlands for analysis. The dominant breast milk FA were oleic acid, constituting 33% of total fatty acids, followed by palmitic acid (26%). Both these FA and the essential FA, linoleic acid (10%) and alpha-linolenic acid (0.4%), showed no significant changes from transitional to mature milk. Breast milk ratio of n-6:n-3 polyunsaturated fatty acids (PUFA) was comparatively high, exceeding 10 throughout the lactation period, suggesting a healthier balance of PUFA intake is needed in pregnancy and at postpartum.

The Importance of Lactose in the Human Diet: Outcomes of a Mexican Consensus Meeting.

Lactose is a unique component of breast milk, many infant formulas and dairy products, and is widely used in pharmaceutical products. In spite of that, its role in human nutrition or lactose intolerance is generally not well-understood. For that reason, a 2-day-long lactose consensus meeting with health care professionals was organized in Mexico to come to a set of statements for which consensus could be gathered. Topics ranging from lactase expression to potential health benefits of lactose were introduced by experts, and that was followed by a discussion on concept statements. Interestingly, lactose does not seem to induce a neurological reward response when consumed. Although lactose digestion is optimal, it supplies galactose for liver glycogen synthesis. In infants, it cannot be ignored that lactose-derived galactose is needed for the synthesis of glycosylated macromolecules. At least beyond infancy, the low glycemic index of lactose might be metabolically beneficial. When lactase expression decreases, lactose maldigestion may lead to lactose intolerance symptoms. In infancy, the temporary replacing of lactose by other carbohydrates is only justified in case of severe intolerance symptoms. In those who show an (epi)genetic decrease or absence of lactase expression, a certain amount (for adults mostly up to 12 g per portion) of lactose can still be consumed. In these cases, lactose shows beneficial intestinal-microbiota-shaping effects. Avoiding lactose-containing products may imply a lower intake of other important nutrients, such as calcium and vitamin B12 from dairy products, as well as an increased intake of less beneficial carbohydrates.

Potential Biomarkers for Fat from Dairy and Fish and Their Association with Cardiovascular Risk Factors: Cross-sectional Data from the LifeLines Biobank and Cohort Study.

Dairy fat intake, reflected by the biomarkers C14:0, C15:0, C17:0, trans-C16:1 (n-7), trans-C18:1 (n-7) and CLA, may have beneficial effects on cardiovascular health. It has, however, been questioned whether this association is genuine, since C15:0 and C17:0 are also biomarkers from fish. We investigated whether the above biomarkers are reliable markers for dairy fat intake in 864 healthy subjects. Subsequently, we explored the association between these biomarkers and cardiovascular risk factors. Intakes of dairy and fish were determined by Food Frequency Questionnaires FFQs. Fatty acids were analyzed in plasma triglycerides (TG) and phospholipids (PL). Median intakes of dairy and fish fat were 12.3 (8.4-17.4) g/day and 1.14 (0.53-1.75) g/day. All fatty acids, except TG C17:0, were associated with dairy fat (std.ß range TG: 0.12 for C14:0 till 0.25 for C15:0 and Trans-C18:1 (n-7); and std.ß range PL: 0.12 for C17:0 and Trans-C16:1 (n-7) till 0.24 for Trans-C18:1 (n-7) and CLA; p < 0.001). TG C17:0 was associated with fish fat (std.ß = 0.08; p = 0.03), whereas PL C17:0 was not. Associations remained after adjustment for fish/dairy fat intake. Strongest inverse associations with biological variables were found with PL C17:0 and Trans-C18:1 (n-7) (Std.ßs: waist circumference: -0.18, p < 0.001 and -0.10, p < 0.05; BMI: -0.17, p < 0.001, -0.11, p < 0.01; glucose: -0.10, p <0.01 and -0.08, p <0.05; high sensitive C-reactive protein (hs-CRP): -0.22, p < 0.001 and -0.16, p < 0.01; uric acid: -0.27, p < 0.001 and -0.24, p < 0.001). In conclusion, fatty acid biomarkers, except plasma TG C17:0, were associated with dairy fat intake, independent of fish fat intake. PL C17:0 and trans-C18:1 (n-7) were inversely associated with adiposity, diabetes, inflammation and uric acid.

Circulating fatty acids as biomarkers of dairy fat intake: data from the lifelines biobank and cohort study.

Background: C14:0, C15:0, C17:0 and trans-C16:1(n-7) are often used as biomarkers for dairy fat intake. Trans-C18:1(n-7) and CLA, two fatty acids which are also present in dairy, have hardly been explored. We investigated whether trans-C18:1(n-7) and CLA can enrich the existing biomarker portfolio. Methods: Data were obtained from Lifelines (n = 769). Dairy fat intake was determined by FFQ. Fatty acids were measured in fasting plasma triglycerides (TG), phospholipids (PL) and cholesterol esters (CE). Results: Median (25th-75th percentile) intakes of dairy and dairy fat were 322(209-447) and 12.3(8.4-17.4) g/d respectively. A pilot study showed that trans-C18:1(n-7) and CLA were only detectable in TG and PL. Of the established markers, TG C15:0 was most strongly associated with dairy fat intake (standardized ß (std.ß) = 0.286, R2 = 0.111). Of the less established markers, TG trans-C18:1(n-7) was most strongly associated with dairy fat intake (Std.ß = 0.292, R2 = 0.115), followed by PL CLA (Std.ß = 0.272, R2 = 0.103) and PL trans-C18:1(n-7) (Std.ß = 0.269, R2 = 0.099). In TG, a combination of C15:0 and trans-C18:1(n-7) performed best (R2 = 0.128). In PL, a combination of C14:0, C15:0, trans-C18:1(n-7) and CLA performed best (R2 = 0.143). Conclusion: Trans-C18:1(n-7) and CLA can be used as biomarkers of dairy fat intake. Additionally, combining established with less established markers allowed even stronger predictions for dairy fat intake.

Influence of daily 10-85 µg vitamin D supplements during pregnancy and lactation on maternal vitamin D status and mature milk antirachitic activity.

Pregnant and lactating women and breastfed infants are at risk of vitamin D deficiency. The supplemental vitamin D dose that optimises maternal vitamin D status and breast milk antirachitic activity (ARA) is unclear. Healthy pregnant women were randomised to 10 (n 10), 35 (n 11), 60 (n 11) and 85 (n 11) µg vitamin D3/d from 20 gestational weeks (GW) to 4 weeks postpartum (PP). The participants also received increasing dosages of fish oil supplements and a multivitamin. Treatment allocation was not blinded. Parent vitamin D and 25-hydroxyvitamin D (25(OH)D) were measured in maternal plasma at 20 GW, 36 GW and 4 weeks PP, and in milk at 4 weeks PP. Median 25(OH)D and parent vitamin D at 20 GW were 85 (range 25-131) nmol/l and 'not detectable (nd)' (range nd-40) nmol/l. Both increased, seemingly dose dependent, from 20 to 36 GW and decreased from 36 GW to 4 weeks PP. In all, 35 µg vitamin D/d was needed to increase 25(OH)D to adequacy (80-249 nmol/l) in >97·5 % of participants at 36 GW, while >85 µg/d was needed to reach this criterion at 4 weeks PP. The 25(OH)D increments from 20 to 36 GW and from 20 GW to 4 weeks PP diminished with supplemental dose and related inversely to 25(OH)D at 20 GW. Milk ARA related to vitamin D3 dose, but the infant adequate intake of 513 IU/l was not reached. Vitamin D3 dosages of 35 and >85 µg/d were needed to reach adequate maternal vitamin D status at 36 GW and 4 weeks PP, respectively.

Fatty acids as biomarkers of total dairy and dairy fat intakes: a systematic review and meta-analysis.

Context: Dairy intake in humans is commonly assessed using questionnaires, but the data collected are often biased. As a result, there is increasing interest in biomarkers of dairy fat. To date, there has been no overview of the fatty acids suitable for use as biomarkers of dairy fat intake. Objective: This systematic review and meta-analysis of observational studies was performed to identify circulating fatty acids as biomarkers of total dairy and dairy fat intakes in the general population. Data Sources: MEDLINE, Embase, and Web of Knowledge databases were searched for eligible studies published until June 2017. Study Selection: Articles were included when a correlation between circulating dairy fatty acids and intakes of total dairy and dairy fat was found, as measured by dietary assessment tools. Data Extraction: Two authors extracted data independently and assessed the risk of bias. An adapted form of the Newcastle-Ottawa Scale was used for quality assessment. Results: Data were pooled using the random-effects model. Meta-analysis revealed that the fatty acids in plasma/serum were significantly correlated with intakes of total dairy (C14:0 [r = 0.15; 95%CI, 0.11 - 0.18], C15:0 [r = 0.20; 95%CI, 0.13 - 0.27], and C17:0 [r = 0.10; 95%CI, 0.03 - 0.16] and dairy fat (C14:0 [r = 0.16; 95%CI, 0.10 - 0.22], C15:0 [r = 0.33; 95%CI, 0.27 - 0.39], C17:0 [r = 0.19; 95%CI, 0.14 - 0.25], and trans-C16:1n-7 [r = 0.21; 95%CI, 0.14 - 0.29). Conclusions: C14:0, C15:0, C17:0, and trans-C16:1n-7 were identified as biomarkers of total dairy and dairy fat intakes in the general population. In light of the suboptimal measurement techniques used in some studies, correlations with trans-C18:1n-7 and conjugated linoleic acid require further investigation.

Regional variations in human milk oligosaccharides in Vietnam suggest FucTx activity besides FucT2 and FucT3.

Breastfeeding is the normal way of providing young infants with the nutrients they need for healthy growth and development (WHO). Human milk oligosaccharides (hMOS) constitute a highly important class of nutrients that are attracting strong attention in recent years. Several studies have indicated that hMOS have prebiotic properties, but also are effective in anti-adhesion of pathogens, modulating the immune system and providing nutrients for brain growth and development. Most of the latter functions seem to be linked to the presence of fucose-containing immunodeterminant epitopes, and Neu5Ac-bearing oligosaccharides. Analysis of hMOS isolated from 101 mothers' milk showed regional variation in Lewis- and Secretor based immunodeterminants. Lewis-negative milk groups could be sub-divided into two sub-groups, based on the activity of a third and hitherto unidentified fucosyltransferase enzyme. Analysis of hMOS remaining in faeces showed three sub-groups based on hMOS surviving passage through the gut, full consumption, specific partial consumption and non-specific partial consumption, fitting previous findings.

Intermittent living; the use of ancient challenges as a vaccine against the deleterious effects of modern life - A hypothesis.

Chronic non-communicable diseases (CNCD) are the leading cause of mortality in developed countries. They ensue from the sum of modern anthropogenic risk factors, including high calorie nutrition, malnutrition, sedentary lifestyle, social stress, environmental toxins, politics and economic factors. Many of these factors are beyond the span of control of individuals, suggesting that CNCD are inevitable. However, various studies, ours included, show that the use of intermittent challenges with hormetic effects improve subjective and objective wellbeing of individuals with CNCD, while having favourable effects on immunological, metabolic and behavioural indices. Intermittent cold, heat, fasting and hypoxia, together with phytochemicals in multiple food products, have widespread influence on many pathways related with overall health. Until recently, most of the employed challenges with hormetic effects belonged to the usual transient live experiences of our ancestors. Our hypothesis; we conclude that, whereas the total inflammatory load of multi-metabolic and psychological risk factors causes low grade inflammation and aging, the use of intermittent challenges, united in a 7-10 days lasting hormetic intervention, might serve as a vaccine against the deleterious effects of chronic low grade inflammation and it's metabolic and (premature) aging consequences.

Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case-Control Study.

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21-69 years, 21 males) and 99 age- and sex-matched controls (19-65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the "low T3 syndrome," was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00-6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of "non-thyroidal illness syndrome" and "low T3 syndrome" experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated.

Milk vitamin D in relation to the 'adequate intake' for 0-6-month-old infants: a study in lactating women with different cultural backgrounds, living at different latitudes.

Breast-fed infants are susceptible to vitamin D deficiency rickets. The current vitamin D 'adequate intake' (AI) for 0-6-month-old infants is 10 µg/d, corresponding with a human milk antirachitic activity (ARA) of 513 IU/l. We were particularly interested to see whether milk ARA of mothers with lifetime abundant sunlight exposure reaches the AI. We measured milk ARA of lactating mothers with different cultural backgrounds, living at different latitudes. Mature milk was derived from 181 lactating women in the Netherlands, Curaçao, Vietnam, Malaysia and Tanzania. Milk ARA and plasma 25-hydroxyvitamin D (25(OH)D) were analysed by liquid-chromatography-MS/MS; milk fatty acids were analysed by GC-flame ionisation detector (FID). None of the mothers reached the milk vitamin D AI. Milk ARA (n; median; range) were as follows: Netherlands (n 9; 46 IU/l; 3-51), Curaçao (n 10; 31 IU/l; 5-113), Vietnam: Halong Bay (n 20; 58 IU/l; 23-110), Phu Tho (n 22; 28 IU/l; 1-62), Tien Giang (n 20; 63 IU/l; 26-247), Ho-Chi-Minh-City (n 18; 49 IU/l; 24-116), Hanoi (n 21; 37 IU/l; 11-118), Malaysia-Kuala Lumpur (n 20; 14 IU/l; 1-46) and Tanzania-Ukerewe (n 21; 77 IU/l; 12-232) and Maasai (n 20; 88 IU/l; 43-189). We collected blood samples of these lactating women in Curaçao, Vietnam and from Tanzania-Ukerewe, and found that 33·3 % had plasma 25(OH)D levels between 80 and 249·9 nmol/l, 47·3 % between 50 and 79·9 nmol/l and 19·4 % between 25 and 49·9 nmol/l. Milk ARA correlated positively with maternal plasma 25(OH)D (range 27-132 nmol/l, r 0·40) and milk EPA+DHA (0·1-3·1 g%, r 0·20), and negatively with latitude (2°S-53°N, r -0·21). Milk ARA of mothers with lifetime abundant sunlight exposure is not even close to the vitamin D AI for 0-6-month-old infants. Our data may point at the importance of adequate fetal vitamin D stores.

Corrigendum to "Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin"".

[This corrects the article DOI: 10.1155/2016/6935123.].

Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study.

Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. We assessed the prevalence of functional vitamin K insufficiency, as derived from plasma desphospho-uncarboxylated MGP (dp-ucMGP), and investigated whether plasma dp-ucMGP is associated with all-cause and cardiovascular mortality in a large general population-based cohort. We included 4275 subjects (aged 53 ± 12 years, 46.0% male) participating in the prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. The prevalence of functional vitamin K insufficiency (i.e., dp-ucMGP > 500 pmol/L) was 31% in the total study population. This prevalence was significantly higher among elderly and subjects with comorbidities like hypertension, type 2 diabetes, chronic kidney disease, and cardiovascular disease (~50%). After 10 years of follow-up, 279 subjects had died, with 74 deaths attributable to cardiovascular causes. We found significant J-shaped associations of plasma dp-ucMGP with all-cause (linear term: hazard ratio (HR) (95% confidence interval (CI)) = 0.20 (0.12-0.33), p < 0.001; squared term: 1.14 (1.10-1.17), p < 0.001) and cardiovascular mortality (linear term: 0.12 (0.05-0.27), p < 0.001; squared term: 1.17 (1.11-1.23), p < 0.001). These associations remained significant after adjustment for potential confounders. Whether the correction of vitamin K insufficiency improves health outcomes needs to be addressed in future prospective intervention studies.