Remko S. Kuipers

Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l.

Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet

Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein < 35 energy % (en%) and linoleic acid (LA) >1.0 en%), at known hunter-gatherer plant/animal food intake ratios (range 70/30-30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter-gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25-29), moderate-to-high fat (30-39) and moderate carbohydrates (39-40). The fatty acid composition was SFA (11.4-12.0), MUFA (5.6-18.5) and PUFA (8.6-15.2). The latter was high in α-linolenic acid (ALA) (3.7-4.7 en%), low in LA (2.3-3.6 en%), and high in long-chain PUFA (LCP; 4.75-25.8 g/d), LCP n-3 (2.26-17.0 g/d), LCP n-6 (2.54-8.84 g/d), ALA/LA ratio (1.12-1.64 g/g) and LCP n-3/LCP n-6 ratio (0.84-1.92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and recommended intakes might be important factors underlying the aetiology of common Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials.

Maternal DHA Equilibrium during Pregnancy and Lactation Is Reached at an Erythrocyte DHA Content of 8 g/100 g Fatty Acids

Low long-chain PUFA (LC-PUFA, or LCP) consumption relates to suboptimal neurodevelopment, coronary artery disease, and [postpartum (PP)] depression. Maternal-to-infant LCP transport during pregnancy and lactation is at the expense of maternal status, a process known as biomagnification. Despite biomagnification, maternal and infant LCP status generally declines during lactation. To assess the 1) turning point of biomagnification [level from which maternal (m)LCP status exceeds infant (i)LCP status]; 2) LCP equilibrium (steady-state-level from which mRBC-LCP stop declining during lactation); 3) corresponding iLCP-status; and 4) the relationship between RBC-DHA and RBC-arachidonic acid (AA), we measured RBC-fatty acids in 193 Tanzanian mother-infant pairs with no, intermediate (2-3 times/wk), and high (4-5 times/wk) freshwater fish consumption at delivery and after 3 mo of exclusive breast-feeding. At 3 mo, mRBC-DHA was lower than the corresponding iRBC-DHA up to a mRBC-DHA of 7.9 g%. mRBC-DHA equilibrium, with equivalent mRBC-DHA at both delivery and at 3 mo PP, occurred at 8.1 g%. This mRBC-DHA equilibrium of 8.1 g% corresponded with an iRBC-DHA of 7.1-7.2 g% at delivery that increased to 8.0 g% at 3 mo. We found between-group differences in mRBC-AA; however, no differences in iRBC-AA were observed at delivery or 3 mo. Relations between RBC-DHA and RBC-AA were bell-shaped. We conclude that, at steady-state LCP intakes during lactation: 1) biomagnification occurs up to 8 g% mRBC-DHA; 2) mRBC-DHA equilibrium is reached at 8 g%; 3) mRBC-DHA equilibrium corresponds with an iRBC-DHA of 7 g% at delivery and 8 g% after 3 mo; 4) unlike RBC-DHA, mRBC-AA and iRBC-AA are independently regulated in these populations; and 5) bell-shaped RBC-DHA vs. RBC-AA-relations might support uniform iRBC-AA. A (maternal) RBC-DHA of 8 g% might be optimal for infant neurodevelopment and adult cardiovascular disease incidence.

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.

The relation between the omega-3 index and arachidonic acid is bell shaped: Synergistic at low EPA+DHA status and antagonistic at high EPA+DHA status

INTRODUCTION The relation between docosahexaenoic (DHA) and eicosapentaenoic (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and antagonism. MATERIALS AND METHODS Investigate the relation between EPA+DHA and AA in populations with a wide range of EPA+DHA status and across the life cycle. EPA+DHA and AA were determined in erythrocytes (RBC; n=1979), umbilical arteries (UA; n=789) and umbilical veins (UV; n=785). RESULTS In all compartments, notably RBC, the relation between EPA+DHA and AA appeared bell-shaped. Populations with low RBC-EPA+DHA (<2g%) exhibited positive relationships; those with high RBC-EPA+DHA (>8g%) negative relationships. Antagonism in UA and UV could not be demonstrated. CONCLUSION Both synergism and antagonism might aim at a balance between ω6 and ω3 long-chain polyunsaturated fatty acid (LCP) to maintain homeostasis. Synergism might be a feature of low LCPω3 status. AA becomes suppressed by antagonism from an RBC-EPA+DHA >8g%.

Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue.

BACKGROUND Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT). OBJECTIVE & DESIGN To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants. RESULTS From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298 mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226 mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2 mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55 g%, MUFA decreased from 44 to 41 g%, and PUFA from 10.3 to 4.26 g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193 mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500 g LGA infants were 184 and 402 mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher. CONCLUSION FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature.

Postdelivery changes in maternal and infant erythrocyte fatty acids in 3 populations differing in fresh water fish intakes

INTRODUCTION Long-chain polyunsaturated (LCP) fatty acids (FA) are important during infant development. Mother-to-infant FA-transport occurs at the expense of the maternal status. Maternal and infant FA-status change rapidly after delivery. METHODS Comparison of maternal (mRBC) and infant erythrocyte (iRBC)-FA-profiles at delivery and after 3 months exclusive breastfeeding in relation to freshwater-fish intakes. Approximation of de-novo-lipogenesis (DNL), stearoyl-CoA-desaturase (SCD), elongation-of-very-long-chain-FA-family-member-6 (Elovl-6), delta-5-desaturase (D5D) and delta-6-desaturase (D6D)-enzymatic activities from their product/essential-FA and product/substrate-ratios. RESULTS AND DISCUSSION Increasing iRBC-14:0 derived from mammary-gland DNL. Decreasing mRBC-ω9, but increasing iRBC-ω9, suggest high ω9-FA-transfer via breastmilk. Decreasing (m+i)RBC-16:0, DNL- and SCD-activities, but increasing (m+i)RBC-18:0 and Elovl-6-activity suggest more pronounced postpartum decreases in DNL- and SCD-activities, compared to Elovl-6-activity. Increasing (m+i)RBC-18:3ω3, 20:5ω3, 22:5ω3, 18:2ω6, mRBC-20:4ω6 and (m+i)D5D-activity, but decreasing mRBC-22:6ω3 and (m+i)D6D-activity and dose-dependent changes in iRBC-22:6ω3 confirm that D6D-activity is rate-limiting and 22:6ω3 is important during lactation. Fish-intake related magnitudes of postpartum FA-changes suggest that LCPω3 influence DNL-, SCD- and desaturase-activities.

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

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.

The feasibility of a Paleolithic diet for low-income consumers

Many low-income consumers face a limited budget for food purchases. The United States Department of Agriculture developed the Thrifty Food Plan to address this problem of consuming a healthy diet given a budget constraint. This dietary optimization program uses common food choices to build a suitable diet. In this article, the United States Department of Agriculture data sets are used to test the feasibility of consuming a Paleolithic diet given a limited budget. The Paleolithic diet is described as the diet that humans are genetically adapted to, containing only the preagricultural food groups of meat, seafood, fruits, vegetables, and nuts. Constraints were applied to the diet optimization model to restrict grains, dairy, and certain other food categories. Constraints were also applied for macronutrients, micronutrients, and long-chain polyunsaturated fatty acids. The results show that it is possible to consume a Paleolithic diet given the constraints. However, the diet does fall short of meeting the daily recommended intakes for certain micronutrients. A 9.3% increase in income is needed to consume a Paleolithic diet that meets all daily recommended intakes except for calcium.

Postpartum changes in maternal and infant erythrocyte fatty acids are likely to be driven by restoring insulin sensitivity and DHA status.

INTRODUCTION Perinatal changes in maternal glucose and lipid fluxes and de novo lipogenesis (DNL) are driven by hormones and nutrients. Docosahexaenoic acid (DHA) reduces, whereas insulin augments, nuclear abundance of sterol-regulatory-element-binding-protein-1 (SREBP-1), which promotes DNL, stearoyl-CoA-desaturase (SCD, also Δ9-desaturase), fatty acid-(FA)-elongation (Elovl) and FA-desaturation (FADS). Decreasing maternal insulin sensitivity with advancing gestation and compensatory hyperinsulinemia cause augmented postprandial glucose levels, adipose tissue lipolysis and hepatic glucose- and VLDL-production. Hepatic VLDL is composed of dietary, body store and DNL derived FA. Decreasing insulin sensitivity increases the contribution of FA from hepatic-DNL in VLDL-triacylglycerols, and consequently saturated-FA and monounsaturated-FA (MUFA) in maternal serum lipids increase during pregnancy. Although other authors described changes in maternal serum and RBC essential-FA (EFA) after delivery, none went into detail about the changes in non-EFA and the mechanisms behind -and/or functions of- the observed changes. HYPOTHESIS Postpartum FA-changes result from changing enzymatic activities that are influenced by the changing hormonal milieu after delivery and DHA-status. EMPIRICAL DATA We studied FA-profiles and FA-ratios (as indices for enzymatic activities) of maternal and infant RBC at delivery and after 3 months exclusive breastfeeding in three populations with increasing freshwater-fish intakes. DNL-, SCD- and FADS2-activities decreased after delivery. Elongation-6 (Elovl-6)- and FADS1-activities increased. The most pronounced postpartum changes for mothers were increases in 18:0, linoleic (LA), arachidonic acid (AA) and decreases in 16:0, 18:1ω9 and DHA; and for infants increases in 18:1ω9, 22:5ω3, LA and decreases in 16:0 and AA. Changes were in line with the literature. DISCUSSION Postpartum increases in 18:0, and decreases in 16:0 and 18:1ω9, might derive from reduced insulin-promoted DNL-activity, with more reduced SCD- than Elovl-activity that leaves more 16:0 to be converted to 18:0 (Elovl-activity) than to MUFA (SCD-activity). Postpartum changes in ΣDNL, saturated-FA and MUFA related negatively to RBC-DHA. This concurs with suppression of both SCD- and Elovl-6 activities by DHA, through its influence on SREBP. Infant MUFA and LA increased at expense of their mothers. Sustained transport might be important for myelination (MUFA) and skin barrier development (LA). Maternal postpartum decreases in FADS2-, and apparent increases in FADS1-activity, together with increases in LA, AA, and 22:5ω3, but decrease in DHA, confirm that FADS2 is rate limiting in EFA-desaturation. Maternal LA and AA increases might be the result of rerouting from transplacental transfer to the incorporation into milk lipids and discontinued placental AA-utilization. IMPLICATIONS Perinatal changes in maternal and infant FA status may be strongly driven by changing insulin sensitivity and DHA status.