Thrombosis within the left anterior descending coronary artery and left ventricle after high-dose nitrous oxide use.

We present a man in his 30s with acute anterior myocardial infarction due to thrombotic occlusion of the left anterior descending artery and subsequent left ventricular thrombus formation after high-dose recreational use of nitrous oxide (N2O). Initial questioning for use of illicit substances was negative, but low vitamin B12 levels and severely elevated homocysteine levels prompted us to interrogate for the use of laughing gas. On questioning, the patient admitted to have used this substance, which he presumed to be innocent. Neither percutaneous coronary intervention with balloon dilatation nor intravenous glycoprotein IIb/IIIa receptor antagonist, nor continuous use of anticoagulation and double antiplatelet therapy resulted in thrombus resolution. Due to a severely reduced left ventricular function, despite 3 months on heart failure therapy, the patient is being counselled for intracardiac defibrillator implantation. We conclude that N2O, notably when consumed in conjunction with other proatherogenic substances, is associated with thrombosis: a relation possibly mediated by severe hyperhomocysteinaemia.

Case report of an acute myocardial infarction after high-dose recreational nitrous oxide use: a consequence of hyperhomocysteinaemia?

BACKGROUND: Nitrous oxide (N2O, laughing gas) is increasingly used as a recreational drug and is presumed relatively safe and innocent. It is often being used in combination with other substances, such as cannabis. CASE SUMMARY: A young adult attended the emergency room because of chest pain after recreational use of very high-dose nitrous oxide in combination with cannabis. Electrocardiography demonstrated ST-elevation in the anterior leads. Coronary angiography showed thrombus in the proximal and thrombotic occlusion of the distal left anterior descending coronary artery for which primary percutaneous coronary intervention was attempted. Thrombus aspiration was unsuccessful and the patient was further treated with a glycoprotein IIb/IIIa in addition to dual platelet therapy. Blood results showed low vitamin B12 and folic acid status with concomitant hyperhomocysteinaemia, a known cause of hypercoagulation. Transthoracic echocardiogram showed a moderately reduced left ventricular ejection fraction (LVEF). Three months later, an improvement in LVEF and no recurrent angina or symptoms of heart failure were noticed. DISCUSSION: We report a case of acute myocardial infarction secondary to very high-dose nitrous oxide abuse in combination with cannabis and possible hypoxia. We propose that severe hyperhomocysteinaemia secondary to nitrous oxide-induced vitamin B12 deficiency together with the vasoconstrictive effects of cannabis might pose a seriously increased risk for intracoronary, among others, thrombus formation. In conclusion, we contest the safety and innocence of recreational nitrous oxide (ab)use, notably in the context of other factors increasing the risk of coagulation.

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.

A multidisciplinary reconstruction of Palaeolithic nutrition that holds promise for the prevention and treatment of diseases of civilisation.

Evolutionary medicine acknowledges that many chronic degenerative diseases result from conflicts between our rapidly changing environment, our dietary habits included, and our genome, which has remained virtually unchanged since the Palaeolithic era. Reconstruction of the diet before the Agricultural and Industrial Revolutions is therefore indicated, but hampered by the ongoing debate on our ancestors' ecological niche. Arguments and their counterarguments regarding evolutionary medicine are updated and the evidence for the long-reigning hypothesis of human evolution on the arid savanna is weighed against the hypothesis that man evolved in the proximity of water. Evidence from various disciplines is discussed, including the study of palaeo-environments, comparative anatomy, biogeochemistry, archaeology, anthropology, (patho)physiology and epidemiology. Although our ancestors had much lower life expectancies, the current evidence does neither support the misconception that during the Palaeolithic there were no elderly nor that they had poor health. Rather than rejecting the possibility of 'healthy ageing', the default assumption should be that healthy ageing posed an evolutionary advantage for human survival. There is ample evidence that our ancestors lived in a land-water ecosystem and extracted a substantial part of their diets from both terrestrial and aquatic resources. Rather than rejecting this possibility by lack of evidence, the default assumption should be that hominins, living in coastal ecosystems with catchable aquatic resources, consumed these resources. Finally, the composition and merits of so-called 'Palaeolithic diets', based on different hominin niche-reconstructions, are evaluated. The benefits of these diets illustrate that it is time to incorporate this knowledge into dietary recommendations.

Fatty acid compositions of preterm and term colostrum, transitional and mature milks in a sub-Saharan population with high fish intakes.

BACKGROUND: There are no data on the fatty acid (FA) compositions of preterm and term milks for sub-Saharan African populations with advancing lactation. However, it is generally acknowledged that our ancestors evolved in sub-Saharan East-Africa, where they inhabited the land-water ecosystems. METHODS: We compared the FA-compositions of preterm (28-36 weeks) and term (37-42) colostrum (2-5 day), transitional (6-15) and mature (16-56) milks in rural African women with stable dietary habits and lifelong high freshwater fish intakes. RESULTS: From colostrum to mature milk: the median docosahexaenoic acid (DHA) content decreased from 1.11 to 0.75; and arachidonic acid (AA) from 0.93 to 0.69 g% in preterm milk. In term milk, DHA decreased from 0.81 to 0.53 and AA from 1.08 to 0.55 g%. Medium-chain saturated-FA (MCSAFA) increased from 16.9 to 33.7, and 7.92-29.0 g%, while mono-unsaturated FA (MUFA) decreased from 32.5 to 22.6, and 40.0-26.5 g%, in preterm and term milk, respectively. Consistent with the literature, preterm colostrum contained higher DHA and MCSAFA, and lower MUFA compared to term colostrum. These differences vanished rapidly with advancing lactation. MUFA and MCSAFA were inversely related. CONCLUSIONS: The presently found DHA in preterm colostrum and mature milks and AA in premature mature milk proved the highest reported in the literature so far, as derived from analysis with capillary GC-columns. We confirmed the much higher MCSAFA and lower MUFA contents in milk of rural African, compared to Westernized women. The milk FA composition of this traditional population might show us the FA composition on which our species evolved and consequently to which our genome has become adapted to optimally support (infant) health.

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.

Differences in preterm and term milk fatty acid compositions may be caused by the different hormonal milieu of early parturition.

INTRODUCTION: The hormonal milieus of pregnancy and lactation are driving forces of nutrient fluxes supporting infant growth and development. The decrease of insulin sensitivity with compensatory hyperinsulinemia with advancing gestation, causes adipose tissue lipolysis and hepatic de novo lipogenesis (DNL). SUBJECTS AND METHODS: We compared fatty acid (FA) contents and FA-indices for enzyme activities between preterm (28-36 weeks) and term (37-42) milks, and between colostrum (2-5 days), transitional (6-15) and mature (16-56) milks. We interpreted FA differences between preterm and term milks, and their changes with lactation, in terms of the well known decrease of insulin sensitivity during gestation and its subsequent postpartum restoration, respectively. RESULTS: Compared with term colostrum, preterm colostrum contained higher indices of DNL in the breast (DNL-breast) and medium chain saturated-FA (MCSAFA), and lower DNL-liver and monounsaturated-FA (MUFA). Preterm milk also had higher docosahexaenoic acid (DHA) in colostrum and transitional milk and higher arachidonic acid (AA) in mature milk. Most preterm-term differences vanished with advancing lactation. In both preterm and term milks, DNL-breast and MCSAFA increased with advancing lactation, while DNL-liver, MUFA, long chain SAFA and AA decreased. DHA decreased in term milk. MUFA was inversely related to MCSAFA in all samples, correlated inversely with PUFA in colostrum and transitional milks, but positively in mature milk. MCSAFA correlated inversely with PUFA in mature milk. CONCLUSION: Higher maternal insulin sensitivity at preterm birth may be the cause of lower MUFA (a proxy for DNL-liver) and higher MCSAFA (a proxy for DNL-breast) in preterm colostrum, compared with term colostrum. Restoring insulin sensitivity after delivery may be an important driving force for milk FA-changes in early lactation.

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%.

Higher de novo synthesized fatty acids and lower omega3- and omega6-long-chain polyunsaturated fatty acids in umbilical vessels of women with preeclampsia and high fish intakes.

Umbilical veins (UV) and arteries (UA) of preeclamptic women in Curaçao harbor lower long-chain polyunsaturated fatty acids (LCP). The present aim was to test these findings in Mwanza (Tanzania), whose inhabitants have high LCPomega3 and LCPomega6 intakes from Lake Victoria fish. Women with preeclampsia (n=28) in Mwanza had lower PUFA and higher 20:0 in UV and UA, compared with normotensive/non-proteinuric controls (n=31). Their UV 22:6omega3, 22:4omega6, LCPomega6, omega6, and LCPomega3+omega6 were lower, while saturated FA, potentially de novo synthesized FA (Sigmade novo) and (Sigmade novo)/(LCPomega3+omega6) ratio were higher. Their UA had higher 16:1omega7, omega7, 18:0, and 16:1omega7/16:0. Umbilical vessels in Mwanza had higher 22:6omega3, LCPomega3, omega3, and 16:0, and lower 22:5omega6, 20:2omega6, 18:1omega9, and omega9, compared to those in Curaçao. Preeclampsia in both Mwanza and Curaçao is characterized by lower LCP and higher Sigmade novo. An explanation of this might be placental dysfunction, while the similarity of umbilical vessel FA-abnormalities in preeclamptic and diabetic pregnancies suggests insulin resistance as a common denominator.

Preformed dietary DHA: The answer to a scientific question may in practice become translated to its opposite.

In a previous issue of AJHB, Carlson and Kingston ([2007]: Am J Hum Biol 19:132-141) raised the question whether modern humans need preformed docosahexaenoic acid (DHA) from the aquatic food chain in their diet. The authors concluded that at the moment, there is not sufficient hard evidence to answer this scientific question in a positive way. In our comment on their review, we argue that because results from various studies and trials strongly indicate a positive correlation between preformed dietary DHA and human health and development, it may be a risky strategy to await the ultimate evidence before recommending the inclusion of sufficient seafood or fish oil supplements in the modern human diet.

Long-chain polyunsaturated fatty acids in maternal and infant nutrition.

Homo sapiens has evolved on a diet rich in alpha-linolenic acid and long chain polyunsaturated fatty acids (LCP). We have, however, gradually changed our diet from about 10,000 years ago and accelerated this change from about 100 to 200 years ago. The many dietary changes, including lower intake of omega3-fatty acids, are related to 'typically Western' diseases. After a brief introduction in essential fatty acids (EFA), LCP and their functions, this contribution discusses our present low status of notably LCPomega3 in the context of our rapidly changing diet within an evolutionary short time frame. It then focuses on the consequences in pregnancy, lactation and neonatal nutrition, as illustrated by some recent data from our group. We discuss the concept of a 'relative' EFA/LCP deficiency in the fetus as the outcome of high transplacental glucose flux. This flux may in the fetus augment de novo synthesis of fatty acids, which not only dilutes transplacentally transported EFA/LCP, but also causes competition of de novo synthesized oleic acid with linoleic acid for delta-6 desaturation. Such conditions were encountered by us in mothers with high body mass indices, diabetes mellitus and preeclampsia. The unifying factor might be compromised glucose homeostasis. In search of the milk arachidonic acid (AA) and docosahexaenoic acid (DHA) contents of our African ancestors, we investigated women in Tanzania with high intakes of freshwater fish as only animal lipid source. These women had milk AA and DHA contents that were well above present recommendations for infant formulae. Both studies stimulate rethinking of 'optimal homeostasis'. Subtle signs of dysbalanced maternal glucose homeostasis may be important and observations from current Western societies may not provide us with an adequate basis for dietary recommendations.