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

Use of Salivary Iodine Concentrations to Estimate the Iodine Status of Adults in Clinical Practice.

BACKGROUND: Measurement of the 24-h urinary iodine concentration or urinary iodine excretion (UIE) is the gold standard to determine iodine status; however, this method is inconvenient. The use of salivary iodine could be a possible alternative since salivary glands express the sodium-iodine symporter. OBJECTIVES: We aimed to establish the correlation between the salivary iodine secretion and UIE, to evaluate the clinical applicability of the iodine saliva measurement. METHODS: We collected 24-h urine and saliva samples from 40 participants ≥18 y: 20 healthy volunteers with no specific diet (group 1), 10 patients with differentiated thyroid cancer with a low dietary intake (<50 µg/d, group 2), and 10 patients with a high iodine status as the result of the use of amiodarone (group 3). Urinary and salivary iodine were measured using a validated inductively coupled plasma MS method. To correct for differences in water content, the salivary iodine concentration (SIC) was corrected for salivary protein and urea concentrations (SI/SP and SI/SU, respectively). The intra- and inter-individual CVs were calculated, and the Kruskal-Wallis test and Spearman's correlation were used. RESULTS: The intra-individual CVs for SIC, SI/SP, and SI/SU were 63.8%, 37.7%, and 26.9%, respectively. The inter-individual CVs for SIC, SI/SP, and SI/SU were 77.5%, 41.6% and 47.0%, respectively. We found significant differences (P < 0.01) in urinary and salivary iodine concentrations between all groups [the 24-h UIE values were 176 µg/d (IQR, 96.1-213 µg/d), 26.0 µg/d (IQR, 22.0-37.0 µg/d), and 10.0*103 µg/d (IQR, 7.57*103-11.4*103 µg/d) in groups 1-3, respectively; the SIC values were 136 µg/L (IQR, 86.3-308 µg/L), 71.5 µg/L (IQR, 29.5-94.5 µg/L), and 14.3*103 µg/L (IQR, 10.6*103-25.6*103 µg/L) in groups 1-3, respectively]. Correlations between the 24-h UIE and SIC, SI/SP, and SI/SU values were strong (ρ = 0.80, ρ = 0.90, and ρ = 0.86, respectively; P < 0.01). CONCLUSIONS: Strong correlations were found between salivary and urinary iodine in adults with different daily iodine intakes. A salivary iodine measurement can be performed to assess the total iodine body pool, with the recommendation to correct for salivary protein or urea.

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.

Folate reference interval estimation in the Dutch general population.

BACKGROUND: Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard. MATERIALS AND METHODS: The folate reference interval was estimated using samples obtained from the Dutch population-based Lifelines cohort. The reference interval was estimated using two methods: a nonparametric estimation combined with bootstrap resampling and by fitting the data to a gamma distribution. The lower reference limit was verified in a patient cohort by combined measurement of folate and homocysteine. RESULTS: Dependent on the method used for estimation and in- or exclusion of individuals younger than 21 years of age, the lower reference limit ranged from 6.8 to 7.3 nmol/L and the upper reference limit ranged from 26 to 38.5 nmol/L. Applying a lower reference limit of 7.3 nmol/L resulted in the following percentage of folate deficiencies over a period of 12 months: general practitioner 15.5% (IQR 4.0%), general hospital 12.8% (IQR 5.3%), academic hospital 9.6% (IQR 4.3%). CONCLUSIONS: We estimated the folate reference interval in the Dutch general population which is not affected by a folic acid fortification program and verified the obtained lower reference limit by homocysteine measurements. Based on our results, we propose a folate reference interval independent of age of 7.3-38.5 nmol/L.

Development and validation of a LC-MS/MS method for the establishment of reference intervals and biological variation for five plasma steroid hormones.

BACKGROUND: With liquid chromatography-tandem mass spectrometry (LC-MS/MS) increasingly being used for the quantification of steroid hormones, there is a need for studies that re-establish reference intervals and biological variation in well-defined cohorts. METHODS: A plasma steroid hormone profiling method using LC-MS/MS for quantification of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and dihydrotestosterone was developed and validated. For reference interval assessment, 280 well-characterized healthy subjects from the LifeLines cohort were selected, including 40 women using oral contraceptive pills (OCP). The biological variation was examined in 30 healthy individuals. Samples were collected over a period of 4 months with 4 week intervals. RESULTS: The developed method proved to be robust and sensitive. The reference interval levels in men are higher, whereas in women the levels tend to decrease with increasing age. In addition, women using OCP had lower levels of 17-OH-progesterone and androstenedione. The biological variation is generally higher in women compared to men, especially with regard to the inter-individual variation. CONCLUSIONS: The gender-specific determination of the reference intervals, together with the observation that the biological variation demonstrated a high degree of variation, allows interpretation of data on individual and group level for improved biochemical characterization of patients in clinical practice.

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.

Iodine status during pregnancy and lactation: a pilot study in the Netherlands.

BACKGROUND: Iodine deficiency occurs in West European countries. Iodine is important for brain development of the foetus and infant. The current iodine status of pregnant and lactating Dutch women is unknown. METHODS: In a pilot study we examined the iodine status of 36 women. From 20 gestational weeks (GW) until 4 weeks postpartum, they ingested 150 µg iodine/day in the form of a multivitamin supplement for pregnant and lactating women. Twenty-four hour urine samples were collected at 20 and 36 GW and at 4 weeks postpartum. A breast milk sample was collected at 4 weeks postpartum. Iodine concentrations were analysed by inductively coupled plasma-mass spectrometry. Cut-off values for the urinary iodine concentration (UIC) for pregnant and lactating women are 150 and 100 µg/l, respectively. Adequate intakes (AI) of iodine for infants aged 0-6 months are 1.1 µmol/l (Institute of Medicine recommendations) or 0.5 µmol/l (Nordic Councilrecommendations). RESULTS: The median UICs (percentages below cut-off) were 102 µg/l (83%) at 20 GW, 144 µg/l (56%) at 36 GW and 112 µg/l (40%) at 4 weeks postpartum. The median breast milk iodine concentration was 1.2 µmol/l (range 0.5-3.0); 33% and 0% of the infants had estimated iodine intakes below the IOM-AI and Nordic-AI, respectively. CONCLUSION: This pilot study suggested a high prevalence of iodine deficiency during pregnancy. Daily supplementation of 150 µg iodine from 20 GW might be insufficient to reach maternal iodine adequacy. The median breast milk iodine concentration seems adequate. Further studies, using a representative sample of the Dutch population, are needed to establish the current Dutch iodine status of pregnant and lactating women.

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.

Fish oil supplemental dose needed to reach 1g% DHA+EPA in mature milk.

INTRODUCTION: Erythrocyte (RBC) DHA+EPA is considered optimal at 8g%. Mothers with lifetime high fish intakes exhibiting this status produce milk with about 1g% DHA+EPA. We established DHA+EPA supplemental dosages needed to augment RBC DHA+EPA to 8g% and milk DHA+EPA to 1g%. MATERIALS AND METHODS: Pregnant women were randomly allocated to DHA+EPA dosages of: 225+90 (n=9), 450+180 (n=9), 675+270 (n=11) and 900+360 (n=7) mg/day. Samples were collected at 20 and 36 gestational weeks and 4 weeks postpartum. RESULTS: Linear regression revealed needed dosages rounded at 750mg/day to reach 8g% RBC DHA+EPA and 1000mg/day for 1g% milk DHA+EPA. RBC DHA+EPA increment depended on baseline values. There was no effect on milk AA, but milk EPA/AA ratio increased. CONCLUSION: Women with an RBC DHA+EPA status of 5.5g% need 750 and 1000mg DHA+EPA/day to reach 8g% RBC DHA+EPA at the pregnancy end and 1g% mature milk DHA+EPA, respectively.

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.

The relation of saturated fatty acids with low-grade inflammation and cardiovascular disease.

The mantra that dietary (saturated) fat must be minimized to reduce cardiovascular disease (CVD) risk has dominated nutritional guidelines for decades. Parallel to decreasing intakes of fat and saturated fatty acids (SFA), there have been increases in carbohydrate and sugar intakes, overweight, obesity and type 2 diabetes mellitus. The "lipid hypothesis" coined the concept that fat, especially SFA, raises blood low-density lipoprotein-cholesterol and thereby CVD risk. In view of current controversies regarding their adequate intakes and effects, this review aims to summarize research regarding this heterogenic group of fatty acids and the mechanisms relating them to (chronic) systemic low-grade inflammation, insulin resistance, metabolic syndrome and notably CVD. The intimate relationship between inflammation and metabolism, including glucose, fat and cholesterol metabolism, revealed that the dyslipidemia in Western societies, notably increased triglycerides, "small dense" low-density lipoprotein and "dysfunctional" high-density lipoprotein, is influenced by many unfavorable lifestyle factors. Dietary SFA is only one of these, not necessarily the most important, in healthy, insulin-sensitive people. The environment provides us not only with many other proinflammatory stimuli than SFA but also with many antiinflammatory counterparts. Resolution of the conflict between our self-designed environment and ancient genome may rather rely on returning to the proinflammatory/antiinflammatory balance of the Paleolithic era in consonance with the 21st century culture. Accordingly, dietary guidelines might reconsider recommendations for SFA replacement and investigate diet in a broader context, together with nondietary lifestyle factors. This should be a clear priority, opposed to the reductionist approach of studying the effects of single nutrients, such as SFA.

Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.

PURPOSE: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors. METHODS: In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2. RESULTS: The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (<15 nmol/l) and a variant genotype showed a high prevalence of the metabolic syndrome (66.7%). Mean intima-media thickness of the carotid artery and urinary albumin excretion, both markers of vascular damage, were higher in the group of survivors homozygous or heterozygous variant for rs523349 (0.62 versus 0.57 mm, P = 0.026; 5.6 versus 3.1 mg/24 h, P = 0.017, respectively). No association was found between cardiometabolic status and SNP rs9282858 in SRD5A2. CONCLUSION: Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention.

Patients undergoing elective coronary artery bypass grafting exhibit poor pre-operative intakes of fruit, vegetables, dietary fibre, fish and vitamin D.

CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 µg/d; range 1.9-11.2 µg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 µg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.

Changes in winter depression phenotype correlate with white blood cell gene expression profiles: a combined metagene and gene ontology approach.

In the present study we evaluate the feasibility of gene expression in white blood cells as a peripheral marker for winter depression. Sixteen patients with winter type seasonal affective disorder were included in the study. Blood was taken by venous puncture at three time points; in winter prior and following bright light therapy and in summer. RNA was isolated, converted into cRNA, amplified and hybridized on Illumina® gene expression arrays. The raw optical array data were quantile normalized and thereafter analyzed using a metagene approach, based on previously published Affymetrix gene array data. The raw data were also subjected to a secondary analysis focusing on circadian genes and genes involved in serotonergic neurotransmission. Differences between the conditions were analyzed, using analysis of variance on the principal components of the metagene score matrix. After correction for multiple testing no statistically significant differences were found. Another approach uses the correlation between metagene factor weights and the actual expression values, averaged over conditions. When comparing the correlations of winter vs. summer and bright light therapy vs. summer significant changes for several metagenes were found. Subsequent gene ontology analyses (DAVID and GeneTrail) of 5 major metagenes suggest an interaction between brain and white blood cells. The hypothesis driven analysis with a smaller group of genes failed to demonstrate any significant effects. The results from the combined metagene and gene ontology analyses support the idea of communication between brain and white blood cells. Future studies will need a much larger sample size to obtain information at the level of single genes.

Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol: a mechanistic explanation centered around lifestyle-induced low-grade inflammation.

We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol ratio is a widely used coronary artery disease (CAD) risk factor. Fatty acid status was determined by measurement of fatty acids in serum cholesterol esters and erythrocytes. Data reflecting the influence of fatty acid intakes on serum total cholesterol and lipoprotein cholesterol were obtained from documented intervention studies. We found that 14:0, 16:0 and saturated fatty acid (SFA) status correlates positively with total cholesterol/HDL cholesterol ratio, while their intakes were unrelated. Linoleic acid and polyunsaturated fatty acid (PUFA) status and PUFA intake exhibited negative relations with the total cholesterol/HDL cholesterol ratio. These data suggest that a high SFA status, not a high SFA intake, is associated with increased CAD risk, while both high linoleic acid status and PUFA status are associated with reduced CAD risk. Consequently, the total cholesterol/HDL cholesterol ratio is a questionable risk marker since meta-analyses of randomized controlled trials show that partial dietary replacement of SFA for linoleic acid, the dominating dietary PUFA, does not change CAD risk. We conclude that many lifestyle factors, not SFA intake alone, determine SFA status, and suggest that interaction with many other lifestyle factors determines whether SFA status has a relevant contributing effect in low-grade inflammation, lipoprotein changes and CAD risk. The present outcome may teach us to consider the health effects of the entire diet together with many nondietary lifestyle factors, opposite to the reductionist approach of studying the effects of single nutrients, SFA and PUFA included.

Interrelationships between maternal DHA in erythrocytes, milk and adipose tissue. Is 1 wt% DHA the optimal human milk content? Data from four Tanzanian tribes differing in lifetime stable intakes of fish.

Little is known about the interrelationships between maternal and infant erythrocyte-DHA, milk-DHA and maternal adipose tissue (AT)-DHA contents. We studied these relationships in four tribes in Tanzania (Maasai, Pare, Sengerema and Ukerewe) differing in their lifetime intakes of fish. Cross-sectional samples were collected at delivery and after 3 d and 3 months of exclusive breast-feeding. We found that intra-uterine biomagnification is a sign of low maternal DHA status, that genuine biomagnification occurs during lactation, that lactating mothers with low DHA status cannot augment their infants' DHA status, and that lactating mothers lose DHA independent of their DHA status. A maternal erythrocyte-DHA content of 8 wt% was found to correspond with a mature milk-DHA content of 1·0 wt% and with subcutaneous and abdominal (omentum) AT-DHA contents of about 0·39 and 0·52 wt%, respectively. Consequently, 1 wt% DHA might be a target for Western human milk and infant formula that has milk arachidonic acid, EPA and linoleic acid contents of 0·55, 0·22 and 9·32 wt%, respectively. With increasing DHA status, the erythrocyte-DHA content reaches a plateau of about 9 wt%, and it plateaus more readily than milk-DHA and AT-DHA contents. Compared with the average Tanzanian-Ukerewe woman, the average US woman has four times lower AT-DHA content (0·4 v. 0·1 wt%) and five times lower mature milk-DHA output (301 v. 60 mg/d), which contrasts with her estimated 1·8-2·6 times lower mobilisable AT-DHA content (19 v. 35-50 g).

DHA status is positively related to motor development in breastfed African and Dutch infants.

OBJECTIVES: Docosahexaenoic (DHA) and arachidonic (AA) acids are important for neurodevelopment. We investigated the relation between erythrocyte (RBC) DHA and AA contents and neurological development, by assessment of General Movements (GMs), in populations with substantial differences in fish intakes. METHODS: We included 3-month-old breastfed infants of three Tanzanian tribes: Maasai (low fish, n = 5), Pare (intermediate fish, n = 32), and Sengerema (high fish, n = 60); and a Dutch population (low-intermediate, fish, n = 15). GMs were assessed by motor optimality score (MOS) and the number of observed movement patterns (OMP; an MOS sub-score). RBC-DHA and AA contents were determined by capillary gas chromatography. RESULTS: We found no between-population differences in MOS. OMP of Sengerema infants (high fish) was higher than OMP of Dutch infants (low-intermediate fish). MOS related to age. OMP related positively to infant age (P < 0.001) and RBC-DHA (P = 0.015), and was unrelated to ethnicity and RBC-AA. DISCUSSION: The positive relation between RBC-DHA and the number of observed movement patterns of 3-month old infants might reflect the connection of DHA with motor development.

Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context.

In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to "nurture" than "nature," since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for "healthy aging," and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture.