Publications by authors named "Frits Muskiet"

95 Publications

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

Nutrients 2020 Dec 30;13(1). Epub 2020 Dec 30.

Laboratory Medicine, University Medical Center Groningen and University of Groningen, 9713 GZ Groningen, The Netherlands.

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" ( = 8), "early milk" ( = 26) and "mature milk" ( = 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 6:3 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.
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http://dx.doi.org/10.3390/nu13010101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824650PMC
December 2020

C-reactive protein in traditional melanesians on Kitava.

BMC Cardiovasc Disord 2020 12 17;20(1):524. Epub 2020 Dec 17.

Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Jan Waldenströms gata 35, CRC, hus 28 plan 11, 205 02, Malmö, Sweden.

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.
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http://dx.doi.org/10.1186/s12872-020-01812-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745357PMC
December 2020

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

BMC Med 2020 12 10;18(1):380. Epub 2020 Dec 10.

Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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. Log vitamin B12, log eGFR, age, and sex were significantly associated with log MMA in multivariable linear regression analyses (model R = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log 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 (P < 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.
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http://dx.doi.org/10.1186/s12916-020-01853-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726887PMC
December 2020

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

Nutrients 2019 Nov 12;11(11). Epub 2019 Nov 12.

FrieslandCampina, 3818 LEAmersfoort, The Netherlands.

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 B from dairy products, as well as an increased intake of less beneficial carbohydrates.
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http://dx.doi.org/10.3390/nu11112737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893676PMC
November 2019

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.

Nutrients 2019 May 17;11(5). Epub 2019 May 17.

Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.

Dairy fat intake, reflected by the biomarkers C14:0, C15:0, C17:0, trans-C16:1 (-7), trans-C18:1 (-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.β range TG: 0.12 for C14:0 till 0.25 for C15:0 and Trans-C18:1 (-7); and std.β range PL: 0.12 for C17:0 and Trans-C16:1 (-7) till 0.24 for Trans-C18:1 (-7) and CLA; < 0.001). TG C17:0 was associated with fish fat (std. = 0.08; = 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 (-7) (Std.βs: waist circumference: -0.18, < 0.001 and -0.10, < 0.05; BMI: -0.17, < 0.001, -0.11, < 0.01; glucose: -0.10, <0.01 and -0.08, <0.05; high sensitive C-reactive protein (hs-CRP): -0.22, < 0.001 and -0.16, < 0.01; uric acid: -0.27, < 0.001 and -0.24, < 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 (-7) were inversely associated with adiposity, diabetes, inflammation and uric acid.
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http://dx.doi.org/10.3390/nu11051099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566248PMC
May 2019

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

Biomarkers 2019 Jun 14;24(4):360-372. Epub 2019 Mar 14.

a Department of Internal Medicine , University Medical Center Groningen and University of Groningen , Groningen , The Netherlands.

C14:0, C15:0, C17:0 and trans-C16:1(-7) are often used as biomarkers for dairy fat intake. Trans-C18:1(-7) and CLA, two fatty acids which are also present in dairy, have hardly been explored. We investigated whether trans-C18:1(-7) and CLA can enrich the existing biomarker portfolio. Data were obtained from Lifelines ( = 769). Dairy fat intake was determined by FFQ. Fatty acids were measured in fasting plasma triglycerides (TG), phospholipids (PL) and cholesterol esters (CE). 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(-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 β (std.β) = 0.286,  = 0.111). Of the less established markers, TG trans-C18:1(-7) was most strongly associated with dairy fat intake (Std.β = 0.292,  = 0.115), followed by PL CLA (Std.β = 0.272,  = 0.103) and PL trans-C18:1(-7) (Std.β = 0.269,  = 0.099). In TG, a combination of C15:0 and trans-C18:1(-7) performed best ( = 0.128). In PL, a combination of C14:0, C15:0, trans-C18:1(-7) and CLA performed best ( = 0.143). Trans-C18:1(-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.
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http://dx.doi.org/10.1080/1354750X.2019.1583770DOI Listing
June 2019

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

Br J Nutr 2019 02;121(4):426-438

1University of Groningen,University Medical Center Groningen,Department of Laboratory Medicine,PO Box 30.001,9700 RB Groningen,The Netherlands.

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.
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http://dx.doi.org/10.1017/S0007114518003598DOI Listing
February 2019

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

Sci Rep 2018 11 14;8(1):16790. Epub 2018 Nov 14.

Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.

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.
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http://dx.doi.org/10.1038/s41598-018-34882-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235895PMC
November 2018

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

Nutr Rev 2019 01;77(1):46-63

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

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.
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http://dx.doi.org/10.1093/nutrit/nuy048DOI Listing
January 2019

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

Med Hypotheses 2018 Nov 9;120:28-42. Epub 2018 Aug 9.

Laboratory Medicine, University Medical Centre Groningen (UMCG), University of Groningen, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.mehy.2018.08.002DOI Listing
November 2018

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

Front Endocrinol (Lausanne) 2018 20;9:97. Epub 2018 Mar 20.

Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.

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.
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http://dx.doi.org/10.3389/fendo.2018.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869352PMC
March 2018

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

Nutrients 2017 Dec 8;9(12). Epub 2017 Dec 8.

Top Institute Food and Nutrition, 6709 PA Wageningen, The Netherlands.

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), < 0.001; squared term: 1.14 (1.10-1.17), < 0.001) and cardiovascular mortality (linear term: 0.12 (0.05-0.27), < 0.001; squared term: 1.17 (1.11-1.23), < 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.
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http://dx.doi.org/10.3390/nu9121334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748784PMC
December 2017

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.

Br J Nutr 2017 Nov 6;118(10):804-812. Epub 2017 Nov 6.

1Laboratory Medicine,University Medical Center Groningen and University of Groningen,PO Box 30.001, 9700 RB Groningen,The Netherlands.

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.
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http://dx.doi.org/10.1017/S000711451700277XDOI Listing
November 2017

Intake of n-3 fatty acids and long-term outcome in renal transplant recipients: a post hoc analysis of a prospective cohort study.

Br J Nutr 2016 Dec 20;116(12):2066-2073. Epub 2016 Dec 20.

1Internal Medicine,University of Groningen and University Medical Center Groningen,PO Box 30.001, 9700 RB Groningen,The Netherlands.

Supplementation with n-3 fatty acids may improve long-term outcomes of renal transplant recipients (RTR). Recent evidence suggests that EPA and DHA have different outcomes compared with α-linolenic acid (ALA). We examined the prospective associations of EPA-DHA and ALA intakes with graft failure and all-cause mortality in 637 RTR. During 3·1 years (interquartile range 2·7, 3·8) of follow-up, forty-one developed graft failure and sixty-seven died. In age- and sex-adjusted analyses, EPA-DHA and ALA intakes were not associated with graft failure. EPA-DHA intake was not significantly associated with mortality (hazard ratio (HR) 0·79; 95% CI 0·54, 1·15 per 0·1 energy% difference). ALA intake was significantly associated with mortality (HR 1·17; 95% CI 1·04, 1·31 per 0·1 energy% difference). This association remained following adjustments for BMI, proteinuria and intakes of fat, carbohydrate and protein. RTR in the highest tertile of ALA intake exhibited about 2-fold higher mortality risk (HR 2·21; 95% CI 1·23, 3·97) compared with the lowest tertile. In conclusion, ALA intake may be associated with increased mortality in RTR. Future RCT are needed to confirm these results.
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http://dx.doi.org/10.1017/S0007114516004207DOI Listing
December 2016

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

J Nutr Biochem 2016 10 14;36:1-20. Epub 2016 Jan 14.

Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.jnutbio.2015.12.007DOI Listing
October 2016

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

Biomed Res Int 2016 6;2016:6935123. Epub 2016 Jun 6.

Laboratory Medicine, University Medical Center Groningen (UMCG) and University of Groningen, 9713 GZ Groningen, Netherlands.

Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders.
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http://dx.doi.org/10.1155/2016/6935123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913061PMC
February 2017

Measurement of plasma vitamin K1 (phylloquinone) and K2 (menaquinones-4 and -7) using HPLC-tandem mass spectrometry.

Clin Chem Lab Med 2016 Jul;54(7):1201-10

Background: Given the growing interest in the health benefits of vitamin K, there is great need for development of new high-throughput methods for quantitative determination of vitamin K in plasma. We describe a simple and rapid method for measurement of plasma vitamin K1 (phylloquinone [PK]) and K2 (menaquinones [MK]-4 and -7). Furthermore, we investigated the association of fasting plasma vitamin K with functional vitamin K insufficiency in renal transplant recipients (RTR).

Methods: We used HPLC-tandem mass spectrometry with atmospheric pressure chemical ionization for measurement of plasma PK, MK-4, and MK-7. Solid-phase extraction was used for sample clean-up. Mass spectrometric detection was performed in multiple reaction monitoring mode. Functional vitamin K insufficiency was defined as plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.

Results: Lower limits of quantitation were 0.14 nmol/L for PK and MK-4 and 4.40 nmol/L for MK-7. Linearity up to 15 nmol/L was excellent. Mean recoveries were >92%. Fasting plasma PK concentration was associated with recent PK intake (ρ=0.41, p=0.002) and with plasma MK-4 (ρ=0.49, p<0.001). Plasma PK (ρ=0.38, p=0.003) and MK-4 (ρ=0.46, p<0.001) were strongly correlated with plasma triglyceride concentrations. Furthermore, we found that MK-4-triglyceride ratio, but not PK-triglyceride ratio, was significantly associated with functional vitamin K insufficiency (OR 0.22 [0.07-0.70], p=0.01) in RTR.

Conclusions: The developed rapid and easy-to-use LC-MS/MS method for quantitative determination of PK, MK-4, and MK-7 in human plasma may be a good alternative for the labor-intensive and time-consuming LC-MS/MS methods and enables a higher sample throughput.
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http://dx.doi.org/10.1515/cclm-2015-0864DOI Listing
July 2016

Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation.

Behav Neurol 2015 5;2015:569869. Epub 2015 May 5.

Department of Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen, P.O. Box 30.001, 9700 RB Groningen, Netherlands.

In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.
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http://dx.doi.org/10.1155/2015/569869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436444PMC
March 2016

Impact of dietary n-3 polyunsaturated fatty acids on cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J mice.

J Nutr Biochem 2015 Jan 28;26(1):24-35. Epub 2014 Sep 28.

Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands. Electronic address:

Maternal intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is critical during perinatal development of the brain. Docosahexaenoic acid (DHA) is the most abundant n-3 PUFA in the brain and influences neuronal membrane function and neuroprotection. The present study aims to assess the effect of dietary n-3 PUFA availability during the gestational and postnatal period on cognition, brain metabolism and neurohistology in C57BL/6J mice. Female wild-type C57BL/6J mice at day 0 of gestation were randomly assigned to either an n-3 PUFA deficient diet (0.05% of total fatty acids) or an n-3 PUFA adequate diet (3.83% of total fatty acids) containing preformed DHA and its precursor α-linolenic acid. Male offspring remained on diet and performed cognitive tests during puberty and adulthood. In adulthood, animals underwent (31)P magnetic resonance spectroscopy to assess brain energy metabolites. Thereafter, biochemical and immunohistochemical analyses were performed assessing inflammation, neurogenesis and synaptic plasticity. Compared to the n-3 PUFA deficient group, pubertal n-3 PUFA adequate fed mice demonstrated increased motor coordination. Adult n-3 PUFA adequate fed mice exhibited increased exploratory behavior, sensorimotor integration and spatial memory, while neurogenesis in the hippocampus was decreased. Selected brain regions of n-3 PUFA adequate fed mice contained significantly lower levels of arachidonic acid and higher levels of DHA and dihomo-γ-linolenic acid. Our data suggest that dietary n-3 PUFA can modify neural maturation and enhance brain functioning in healthy C57BL/6J mice. This indicates that availability of n-3 PUFA in infant diet during early development may have a significant impact on brain development.
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http://dx.doi.org/10.1016/j.jnutbio.2014.08.002DOI Listing
January 2015

Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study.

Lipids Health Dis 2014 Oct 11;13:160. Epub 2014 Oct 11.

Department Nutrition and Health, Louis Bolk Institute, Hoofdstraat 24, Driebergen, LA 3972, the Netherlands.

Background: The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained.

Methods: Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention.

Results: Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m2. The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this unintended weight loss. No changes were observed for intestinal permeability, inflammation and salivary cortisol.

Conclusions: We conclude that consuming a Palaeolithic-type diet for two weeks improved several cardiovascular risk factors compared to a healthy reference diet in subjects with the metabolic syndrome.

Trial Registration: Nederlands Trial Register NTR3002.
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http://dx.doi.org/10.1186/1476-511X-13-160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210559PMC
October 2014

A fish is not a fish: patterns in fatty acid composition of aquatic food may have had implications for hominin evolution.

J Hum Evol 2014 Dec 26;77:107-16. Epub 2014 Jul 26.

Laboratory Medicine, University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

From c. 2 Ma (millions of years ago) onwards, hominin brain size and cognition increased in an unprecedented fashion. The exploitation of high-quality food resources, notably from aquatic ecosystems, may have been a facilitator or driver of this phenomenon. The aim of this study is to contribute to the ongoing debate on the possible role of aquatic resources in hominin evolution by providing a more detailed nutritional context. So far, the debate has focused on the relative importance of terrestrial versus aquatic resources while no distinction has been made between different types of aquatic resources. Here we show that Indian Ocean reef fish and eastern African lake fish yield on average similarly high amounts of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Hence a shift from exploiting tropical marine to freshwater ecosystems (or vice versa) would entail no material difference in dietary long-chain polyunsaturated fatty acid (LC-PUFA) availability. However, a shift to marine ecosystems would likely mean a major increase in access to brain-selective micronutrients such as iodine. Fatty fish from marine temperate/cold waters yield twice as much DHA and four times as much EPA as tropical fish, demonstrating that a latitudinal shift in exploitation of African coastal ecosystems could constitute a significant difference in LC-PUFA availability with possible implications for brain development and functioning. We conclude that exploitation of aquatic food resources could have facilitated the initial moderate hominin brain increase as observed in fossils dated to c. 2 Ma, but not the exceptional brain increase in later stages of hominin evolution. We propose that the significant expansion in hominin brain size and cognition later on may have been aided by strong directional selecting forces such as runaway sexual selection of intelligence, and nutritionally supported by exploitation of high-quality food resources in stable and productive aquatic ecosystems.
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http://dx.doi.org/10.1016/j.jhevol.2014.04.004DOI Listing
December 2014

Beyond the Paleolithic prescription: commentary.

Nutr Rev 2014 Apr 25;72(4):285-6. Epub 2014 Mar 25.

Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1111/nure.12112DOI Listing
April 2014

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.

J Nutr Biochem 2014 Mar 2;25(3):304-12. Epub 2013 Dec 2.

Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.jnutbio.2013.11.004DOI Listing
March 2014

Lactase persistence and augmented salivary alpha-amylase gene copy numbers might have been selected by the combined toxic effects of gluten and (food born) pathogens.

Med Hypotheses 2014 Mar 15;82(3):326-34. Epub 2014 Jan 15.

Laboratory Medicine, University of Groningen, University Medical Center Groningen (UMCG), P.O. Box 30.001, Groningen, The Netherlands.

Various positively selected adaptations to new nutrients have been identified. Lactase persistence is among the best known, conferring the ability for drinking milk at post weaning age. An augmented number of amylase gene (AMY1) copies, giving rise to higher salivary amylase activity, has been implicated in the consumption of starch-rich foods. Higher AMY1 copy numbers have been demonstrated in populations with recent histories of starchy-rich diets. It is however questionable whether the resulting polymorphisms have exerted positive selection only by providing easily available sources of macro and micronutrients. Humans have explored new environments more than any other animal. Novel environments challenge the host, but especially its immune system with new climatic conditions, food and especially pathogens. With the advent of the agricultural revolution and the concurrent domestication of cattle came new pathogens. We contend that specific new food ingredients (e.g., gluten) and novel pathogens drove selection for lactase persistence and higher AMY gene copy numbers. Both adaptations provide ample glucose for activating the sodium glucose-dependent co-transporter 1 (SGLT1), which is the principal glucose, sodium and water transporter in the gastro-intestinal tract. Their rapid uptake confers protection against potentially lethal dehydration, hyponatremia and ultimately multiple organ failure. Oral rehydration therapy aims at SGLT1 activity and is the current treatment of choice for chronic diarrhoea and vomiting. We hypothesize that lifelong lactase activity and rapid starch digestion should be looked at as the evolutionary covalent of oral rehydration therapy.
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http://dx.doi.org/10.1016/j.mehy.2013.12.020DOI Listing
March 2014

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.

Br J Nutr 2014 Mar 31;111(5):854-66. Epub 2013 Oct 31.

Laboratory Medicine, University Medical Center Groningen (UMCG), Groningen University Hospital, Room Y 3.181, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

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).
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http://dx.doi.org/10.1017/S0007114513003255DOI Listing
March 2014

Yes, we can define an infant's need from the composition of human milk as long as the breastmilk derives from mothers with healthy lifestyles.

Prostaglandins Leukot Essent Fatty Acids 2013 Oct 7;89(5):377. Epub 2013 Sep 7.

Laboratory Medicine, University of Groningen, University Medical Center Groningen (UMCG), Building 33, 2nd floor, Y2. 131; Room 083; Internal Post Code EA61, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.plefa.2013.09.001DOI Listing
October 2013

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

Nutr Neurosci 2014 Apr 26;17(3):97-103. Epub 2013 Nov 26.

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.
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http://dx.doi.org/10.1179/1476830513Y.0000000070DOI Listing
April 2014

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

J Nutr Biochem 2013 Jul 6;24(7):1183-201. Epub 2013 May 6.

Laboratory Medicine, University Medical Center Groningen, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.jnutbio.2013.02.009DOI Listing
July 2013