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The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers ingested two 8.5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6.0 g EPA/d and 5.3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TAG) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL showed a 15-fold increase after 7 d (P < 0.001), while DHA showed a smaller increase (P < 0.01). In CE, EPA also increased (P < 0.05), while DHA did not increase at all. Remarkably, incorporation of DHA into TAG was even higher than that of EPA. Half-life of EPA in PL ranged from 1.63 to 2.31 d (mean 1.97 (SE 0.15) d), whereas mean half-life of EPA in CE was 3.27 (SE 0.56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi-exponential pattern, with a short half-life (< 1 d) in the initial phase and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of > or = 12 h in supplementation studies.

Adenosine 5'-triphosphate (ATP) is a purine nucleotide found in every cell of the human body. In addition to its well established role in cellular metabolism, extracellular ATP and its breakdown product adenosine, exert pronounced effects in a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation and liver glycogen metabolism. These effects are mediated by both P1 and P2 receptors. A cascade of ectonucleotidases plays a role in the effective regulation of these processes and may also have a protective function by keeping extracellular ATP and adenosine levels within physiological limits. In recent years several clinical applications of ATP and adenosine have been reported. In anaesthesia, low dose adenosine reduced neuropathic pain, hyperalgesia and ischaemic pain to a similar degree as morphine or ketamine. Postoperative opioid use was reduced. During surgery, ATP and adenosine have been used to induce hypotension. In patients with haemorrhagic shock, increased survival was observed after ATP treatment. In cardiology, ATP has been shown to be a well tolerated and effective pulmonary vasodilator in patients with pulmonary hypertension. Bolus injections of ATP and adenosine are useful in the diagnosis and treatment of paroxysmal supraventricular tachycardias. Adenosine also allowed highly accurate diagnosis of coronary artery disease. In pulmonology, nucleotides in combination with a sodium channel blocker improved mucociliary clearance from the airways to near normal in patients with cystic fibrosis. In oncology, there are indications that ATP may inhibit weight loss and tumour growth in patients with advanced lung cancer. There are also indications of potentiating effects of cytostatics and protective effects against radiation tissue damage. Further controlled clinical trials are warranted to determine the full beneficial potential of ATP, adenosine and uridine 5'-triphosphate.

In prospective cohort studies an association between fat consumption and breast and colon cancer was not confirmed. Alcoholic beverages enhance the risk of cancer of the oral cavity, pharynx, larynx and oesophagus, while the relation is less well established for cancer in the stomach, pancreas, colon, rectum and breast. Consumption of vegetables and fruits reduces the risk of lung, oesophagus, stomach and pancreatic cancer. Which food components are responsible for this observation is unclear, but beta-carotene does not appear to be responsible. Clinical depletion in cancer patients is a result of metabolic disturbances as a consequence of the cancer and has negative effects on the course of the disease and on the treatment. Altered eating behaviour, food aversion, decreased food intake and loss of body weight may indicate the presence of clinical depletion. Positive effects of (artificial) nutrition as an adjunct to chemoor radiation therapy are very limited, larger but still limited as an adjunct to surgical therapy. It is not justified to allow insufficient food intake to continue during treatment of cancer; early (artificial) nutritional intervention is warranted in those cases. Food requirements of cancer patients and healthy persons apparently do not differ. A well balanced normal diet providing adequate amounts of energy, proteins, vegetables and fruits is therefore advised. Alternative diets, such as the Moerman or Houtsmuller diet, may provide the necessary energy and other specific food components as long as animal proteins (milk, meat, fish) are not omitted completely. There is no evidence that these diets will alter the disease course in a positive way; patients may benefit from the idea that they are contributing to their own health, however. If the physician doubts whether the alternative diet is used voluntarily, or if there are negative effects (social isolation, financial burden) he or she should advise against its continuation.

Food is the major source for polychlorinated biphenyl (PCB) and dioxin accumulation in the human body. Therefore, investigating food habits from early ages until reproductive age (25 years) is important in order to assess exposure risk for the next generation. The objective of this study was to assess the PCB/dioxin exposure and the relative contribution of different foods to total exposure during preschool age. Particularly, the importance of lactational PCB/dioxin exposure vs. dietary exposure until adulthood was investigated. A cohort of 207 children was studied from birth until preschool age. Based on 3 planar PCBs and 17 2,3,7,8-substituted dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) measured in breast milk, a model was developed to calculate the cumulative toxic equivalent (TEQ) intake during breast-feeding (0-1 year). In 3. 5-year-old children, daily dietary intake of planar PCB-TEQ and dioxin-TEQ was measured with a validated food questionnaire. Cumulative TEQ intake from 1 to 5 years was estimated using the PCB- and dioxin-TEQ intake measured with the food questionnaire. Cumulative TEQ intake from 6 to 25 years was estimated using national food consumption and contamination data of PCB- and dioxin-TEQ intake. In toddlers, dairy products contributed 43% to PCB-TEQ and 50% to dioxin-TEQ intake. Meat and meat products contributed 14% and 19%, respectively, and processed foods 23% and 15%, respectively. Breast-feeding for 6 months contributed to the cumulative PCB/dioxin TEQ intake until 25 years of age, 12% in boys and 14% in girls. The daily TEQ intake per kilogram body weight is 50 times higher in breast-fed infants and three times higher in toddlers than in adults. Long-term dietary exposure to PCBs and dioxins in men and women is partly due to breast-feeding (12 and 14%, respectively). After weaning, dairy products, processed foods, and meat are major contributors of PCB and dioxin accumulation until reproductive age. Instead of discouraging breast-feeding, maternal transfer of PCBs and dioxins to the next generation must be avoided by enforcement of strict regulations for PCB and dioxin discharge and by reducing consumption of animal products and processed foods in all ages.

The high divergence between the liver metabolite concentrations and pH values reported in previous quantitative 31P magnetic resonance studies, for instance phosphomonoester (0.7-3.8 mM) and phosphodiester (3.5-9.7 mM), has not been addressed in the literature. To assess what level of discrepancy can be caused by processing and metabolite integration, in this study chemical shift imaging localized 31P magnetic resonance spectra of human liver were quantitated by three methods currently applied in clinical practice: peak areas defined manually by placement of two cursors vs. frequency domain curve fitting with the assumption of either Gaussian or Lorentzian line shapes. Large reproducible differences were found in liver metabolite peak areas but not in pH, indicating that processing and peak integration methods can only explain part of the discrepancies between the results from different institutions.

To study the relationship between diet and growth, a longitudinal anthropometric study was conducted in a Dutch population consuming a macrobiotic diet. Measurements (anthropometry and food habit questionnaire) were taken in 1985 (0-7 y), 1987, and in 1993 (7-16 y, n = 209). Z-scores were calculated for anthropometric measures and changes expressed as the differences between 1993 and the mean of 1985 and 1987. Analysis indicated significant (P < 0.002) catch-up in height [(mean Z-score +/-sEM) +0.59 +/- 0.071 and arm circumference (+0.34 +/- 0.09) for age (boys and girls combined). In 1993, both girls and boys were still significantly (P < 0.05) below the reference for height and sum of four skinfolds for age, and girls were below reference for weight-for-height and arm circumference for age. In girls, multiple regression analyses showed a significant positive effect of the consumption frequency of dairy products on catch-up growth in height, weight and arm circumference, after adjustment for menarche, age, and baseline height, weight and arm circumference (P < 0.05). The addition of moderate amounts of dairy products to a vegan type of diet improved growth of children, especially girls.

The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were detected after fish oil ingestion. The 13C resonances, centered at 14.3, 127.1, and 131.6 ppm, have been assigned to specific carbon groups (CH3-CH2-CH = CH-, CH3-CH2-CH = CH-CH2-, CH3-CH2-CH = CH-CH2-, respectively) in eicosapentaenoic acid (C20:5n-3) and docosahexaenoic (C22:6n-3) DHA. The new lipid resonance observed in the 1H spectra of plasma (0.941 ppm) is consistent with the incorporation of these n-3 fatty acids into lipoprotein particles. The presence of increased EPA and DHA in plasma lipids was confirmed by gas-liquid chromatography. A marked reduction in the intensity of the methylene signal from very low density lipoproteins (VLDL) was also observed with fish oil. This reduction arises from a decrease in plasma triglyceride concentration (ca. 18%) and a reduction in the number of VLDL particles. Transverse relaxation studies of isolated VLDL and low density lipoprotein (LDL) showed significant elevation in the T2 of the -(CH2)n- and CH3- signals from non-n-3 fatty acids. The relaxation characteristics and signal intensity of the novel 1H peak (0.941 ppm) point to the existence of n-3 enriched microenvironments within lipoprotein particles. These findings suggest that incorporation of EPA and DHA into VLDL and LDL, after fish oil ingestion, leads to significant alteration in the molecular architecture of lipoprotein particles.

A 31P chemical shift imaging (CSI) protocol was developed for human liver studies. It is shown that at the commonly used repetition time (TR) of 1 s T1-weighting reduces the integrated intensities of liver phosphate metabolite signals by 18 +/- 15% (inorganic phosphate, Pi) to 46 +/- 10% (phosphodiester, PDE), that is for an RF pulse angle of 60 degrees (weighted average) in liver. The loss in signal-to-noise ratio (S/N) at TR = 20 s, sufficient to eliminate spectral distortions caused by saturation, compared with TR = 1 s (47-65%) can be overcome by using one-dimensional (1D)-phase encoding with a small number of phase-encode steps. The liver spectra obtained by 1D-CSI with 4-step phase-encoding (spatial resolution 10 cm) have the highest S/N and, after multiplication of the PDE signal by a factor of 1.4, closely reflect the liver metabolite levels. It is concluded that clinical 31P MR studies of liver function can be performed without T1-weighting and that the current practice to compromise the MRS quantification of lever metabolites with uncertainties caused by (differential changes in) T1-weighting is not warranted.

Methylmalonic acid and total homocysteine in plasma and serum have previously been used as indicators of intracellular cobalamin function in adults. To assess the usefulness of quantitation of these metabolites in the diagnosis of dietary cobalamin deficiency in infants, they were determined in plasma from 41 infants (aged 10-20 mo) on a macrobiotic diet and in 50 healthy group-matched omnivorous controls. In the macrobiotic infants, both methylmalonic acid and total homocysteine were markedly increased compared with controls (8-fold and 2-fold, respectively). Both metabolites showed an inverse relation to the plasma cobalamin level. The very low cobalamin content of the macrobiotic diet and low plasma cobalamin in macrobiotic infants makes an impaired cobalamin function likely in these infants. We therefore used dietary group as an independent indicator of cobalamin status. Different test parameters for cobalamin status were evaluated by comparing their ability to discriminate between the two dietary groups. Logistic regression analysis showed that methylmalonic acid followed by total homocysteine and cobalamin, in that order, were the strongest predictors of dietary group. Mean corpuscular volume and Hb had low discriminative power. We conclude that the determination of methylmalonic acid and total homocysteine represents a sensitive and specific test for the diagnosis and follow-up of nutritional cobalamin deficiency in infants. Furthermore, the finding of high methylmalonic acid and total homocysteine in plasma of most macrobiotic infants demonstrates a functional cobalamin deficiency in these subjects.

A population-based study on the nutritional status of children consuming macrobiotic diets was carried out in The Netherlands. Participants followed a macrobiotic diet based mainly on whole-grain cereals, pulses, and vegetables. Studies in children aged 0-10 y suggested that growth was retarded mainly between 6 and 18 mo. This was confirmed in a subsequent mixed-longitudinal study (including data on diet, anthropometry, blood chemistry, and pediatric examination) in 4-18 mo-old macrobiotic infants and a matched omnivorous control group. Ubiquitous deficiencies of energy, protein, vitamin B-12, vitamin D, calcium, and riboflavin were detected in macrobiotic infants, leading to retarded growth, fat and muscle wasting, and slower psychomotor development. Breast milk from macrobiotic mothers contained less vitamin B-12, calcium, and magnesium. Supplementation of the macrobiotic diet with fat (minimum 20-25 g/d), fatty fish (minimum 100-150 g/wk), and dairy products (minimum 150-250 g/d) is recommended.

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by omega 3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chow ad libitum were inoculated with 10(6) MAT-LyLu cells (n = 14) or saline (n = 9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumor-bearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7-14 (difference by dietary group: NTB, P < 0.001; TB, P < 0.001). During days 14-21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB, P < 0.003; TB, P = 0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P = 0.05) and mean food intake during the study (P = 0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean +/- SEM 58 +/- 10 g loss, P < 0.001), but not in TB animals on fish oil diets (8 +/- 18 g loss, P = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study the relationship between diet and growth, we have assessed growth patterns in children 0-10 years old on macrobiotic diets. A cross-sectional anthropometric study (0-8 years old children, n = 243) indicated that deviation from the reference growth curve occurred during the weaning period. Between 2 and 4 years there was a partial catch-up for weight and arm circumference but not for height. As a next step, a mixed-longitudinal study was performed in 4-18-month-old macrobiotic infants (n = 53) and matched omnivorous controls (n = 57). For a period of 6 months, data on growth and dietary intake were collected. The data on linear growth supported the findings on growth stagnation observed cross-sectionally. Linear growth was associated with the protein content of the diet, but not with energy intake. On the basis of our findings nutritional modifications to the macrobiotic diet (addition of fat and fish) were recommended for all macrobiotic families. Six months later (two years after the first cross-sectional data collection) the anthropometric study was repeated in the same cohort (n = 194). This follow-up study revealed that children from families which, since the initial study, had increased the consumption of fatty fish, dairy products, or both, had grown in height more rapidly than the remaining children (P < 0.05). Since no indications were found for the presence of adverse social circumstances, infectious diseases or other confounding factors, our data clearly demonstrate that linear growth retardation in children on macrobiotic diets is caused by nutritional deficiencies alone.

Although the reduction of serum triacylglycerol concentrations by dietary fish oil is a well-known effect, the exact mechanism of this effect has not been previously studied in human subjects. Therefore, the aim of this study was (i) to examine the effect of short-term fish oil supplementation on blood concentrations of ketone bodies, free fatty acids and triacylglycerol in healthy humans and (ii) to verify whether the observed relationships between these variables would be consistent with reduced lipolysis and/or enhanced hepatic fatty acid oxidation after fish oil supplementation. Twenty subjects (21-23 years, normal liver function tests) were randomly divided into two groups to supplement their usual diet with either 30 g/d of fish oil (n = 11) or olive oil (n = 9). Venous blood samples were drawn after an overnight fast, before and after 1, 3 and 7 d of fish oil/olive oil supplementation. Blood concentrations of triacylglycerol and free fatty acids decreased consistently after fish oil supplementation; the reduction was already significant after one day of fish oil (P < 0.001 for triacylglycerol and P = 0.01 for free fatty acids). In contrast, neither of these blood values changed after olive oil supplementation (P > 0.10). No significant changes in glucose, insulin or ketone body levels were observed in either group after supplementation. After fish oil, but not after olive oil supplementation, the ratio of blood ketone body levels to free fatty acid levels increased significantly (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour-bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose-6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer.

The effect of omega 3 fatty acids on the metabolism of the normal liver was studied using 31P NMR spectroscopy. Human subjects were examined before and after 1, 3 and 7 days of supplementation with 50 mL fish oil per day (12 g omega 3 fatty acids). 31P NMR spectra (1.6 T) revealed a significant increase in phosphodiester (PDE) to ATP ratios after 1 and 3 days of fish oil. After 7 days, [PDE]/[ATP] ratios at a TR of 1 s had returned to baseline levels, but [PDE]/[ATP] at a TR of 5 s appeared to remain high. Rats were fed diets containing 50% of the energy from fish oil or normal rat chow (controls) for 14 days. 31P NMR liver spectra in vivo (4.7 T) confirmed increased [PDE]/[ATP] in rats fed fish oil compared to controls, although the difference was only statistically significant at a TR of 1.5 s but not at a TR of 8 s. 31P NMR spectra of rat liver extracts (8.7 T) suggested that increased concentrations of glycerophosphocholine and possibly glycerophosphoethanolamine were responsible for rising PDE levels in vivo. Phosphocholine (PC) concentrations were markedly reduced in rat liver after fish oil. The combined rise in glycerophosphocholine and reduction in PC would be consistent with a shift from the phospholipase C to the phospholipase A1/A2 pathway of phosphatidylcholine breakdown after fish oil consumption.

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of L-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34-44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of L-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the beta-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean +/- SEM: 98 +/- 12%, P < 0.005) and [Pi]/[ATP] (-33 +/- 3%, P < 0.001) were observed approximately 45 min after the L-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 +/- 6% (P < 0.05), which was independent of the L-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of L-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after L-alanine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.

The effect of algae (nori and spirulina) and fermented plant foods on the hematological status of vitamin B-12-deficient children was evaluated. Although rising plasma vitamin B-12 concentrations in children consuming only plant foods (0.1-2.7 micrograms vitamin B-12/d) indicated that the vitamin B-12 was absorbed, elevated baseline values of mean corpuscular volume (MCV) further deteriorated. In contrast, MCV improved in children receiving fish containing 0.15-0.5 microgram vitamin B-12/d or a vitamin B-12 supplement. Further studies on the specificity of current vitamin B-12 assays are warranted. It seems unjustified to advocate algae and other plant foods as a safe source of vitamin B-12 because its bioavailability is questionable.

Studies in children fed alternative diets showed that anthropometric parameters and the intake of energy and nutrients by macrobiotic children deviated most from current norms. Therefore weaning practice, growth and haematological status were investigated in 3 age-cohorts of macrobiotic fed infants between 4 and 18 months of age and a control group. A mixed longitudinal design was used for this study. Main findings were a growth retardation which was strongest in the second cohort (8-14 months of age) and related to a diet low in energy density, fat and protein. Haematological data revealed very low vitamin B12 concentrations with consequently low values of haematocrit and red blood cell count and higher values of mean corpuscular volume and mean corpuscular haemaglobin mass in the macrobiotic group. High folate concentrations also seemed to be a consequence of Vitamin B12 deficiency. Iron deficiency was found in 15% of the macrobiotic group vs. no infants in the control group. Nutritional recommendations acceptable within the macrobiotic philosophy are discussed.

As a follow-up of a population-based descriptive study on the nutritional status and growth of infants on macrobiotic diets (n = 53), an intervention study was carried out in 27 selected infants with clear nutritional deficiencies. This intervention program consisted of information on the nutrient content of macrobiotic foods, a regular newsletter, personal advice if needed, and reference to teachers in macrobiotics for further advice. Adaptation of the diet within the scope of current macrobiotic guidelines did not lead to an improvement in nutritional intake, growth and blood values. As a consequence of these findings, the macrobiotic community in the Netherlands and abroad has become more aware of the need for adaptation of the macrobiotic diet. It is recommended to include a source of dietary fat (minimum 20-25 g/day), fatty fish (minimum 100-150 g/wk) and dairy products (minimum 150-250 g/day).

The vitamin D status of 53 Caucasian infants aged 10-20 mo on a macrobiotic diet and 57 matched control infants on omnivorous diets was studied. In late summer (August-November) physical symptoms of rickets were present in 28% of the macrobiotic group; these infants had lower average plasma 25(OH)D concentrations (34.0 +/- 15.3 nmol/L) (mean +/- SD) than did the macrobiotic infants without such symptoms (49.7 +/- 21.9 nmol/L, p less than 0.02). Follow-up of a subsample of 25 macrobiotic infants in March-April revealed physical symptoms of rickets in 55% of the macrobiotic infants. All concentrations in blood were considerably below those in the preceding summer; the average 25(OH)D concentration was 12.3 +/- 4.3 nmol/L. Further analysis indicated that the low availability of calcium in the macrobiotic diet was an independent factor in causing the high prevalence of rickets in summer. Avoidance of milk products in combination with a high fiber intake may damage bone development in young children.

In this first article out of a series of two articles, a critical review of available scientific information on the nutritional consequences of alternative and especially vegan-type food habits in infants and preschool children is presented. This article involves definitions and information on general health indicators, such as the health of mothers during pregnancy and the growth and development of children. Some difficulties in interpreting available literature are also discussed. Many of the available case studies do not seem to be representative for population groups of infants and children fed alternative diets. Population studies mostly lack a control group and do not provide information on whether the sample is representative or not. Because of changing alternative food habits, some studies may be outdated. Alternatively fed toddlers six months to three years old, especially macrobiotics and veganists, seem to be somewhat smaller than their counterparts eating mixed diets, whereas there is some evidence of increased growth after the age of two years. The significance of these differences is not completely clear.

Children who are fed alternative and especially macrobiotic diets have been reported to be smaller and weigh less than their peers fed omnivorous diets. To answer the questions: at what age does growth in children on macrobiotic diets slow down, and is there any return to standards later in childhood, a cross-sectional anthropometric study was performed in the Dutch macrobiotic child population aged 0-8 years (n = 243). Addresses were obtained from macrobiotic organizations and from families already participating in the study. Food habits were checked by a structured food frequency questionnaire. Anthropometric measurements included weight, height, mid-upper arm circumference and triceps and subscapular skinfolds. For each sex, age curves were constructed in comparison to standards. For selected age intervals, standard deviation scores (SDS) were tested for differences from the reference after accounting for confounding variables in a multiple regression model. Reported birth weight was 150 g lower than the Dutch reference; birth weight was positively associated with the consumption frequency of dairy products and fish. During the first 6-8 months of life, SDS were not different from the standard except for arm circumference and skinfolds. From 6-8 months onwards, growth stagnation occurred in both sexes, but was most marked in girls. A minimum level of 1 to 1.5 SD below the P50 of the reference was reached by the age of 18 months. Between 2 and 4 years a partial return towards the P50 occurred for arm circumference and, in boys only, for weight and skinfolds, but not for height. SDS of weight, height and arm circumference were higher in children from families with regular consumption of dairy products than in children from families avoiding dairy products.

A review of four studies examining food consumption growth and development of Dutch children fed on alternative diets is given. A literature study indicated that regarding child nutrition the three important movements in the Netherlands are the ecological movement, the anthroposophics, and the macrobiotics. A study on food consumption, height, and weight in preschool children fed these diets showed that the group of macrobiotic children were most at risk. Antropometric data collected in a cross-sectional study with 300 macrobiotic-fed children aged 0-8 y showed that the growth curves for boys and girls deviated from the Dutch standard curves after approximately 5 mo of age. There was no catch-up growth. In a selected sample of this latter group (43 children aged 4-6 y) mental development was measured by the Snijders-Oomen-Nonverbal intelligence test. The results of this test did not indicate an abnormal mental development for this age group of macrobiotic children.

This article, which is the second in a series of two articles, discusses available scientific information on the nutritional status of infants and preschool children on alternative diets with regard to calcium, iron, vitamin B12 and D. Some favourable aspects of alternative food habits in such children are also mentioned. Most studies report low intakes of vitamin D and in vegan and macrobiotic children also of calcium and vitamin B12, but it cannot be excluded that some alternative sources of these nutrient may have been missed. Deficiencies have been described for vitamin D and B12 but the evidence is often unconvincing. For example, exposure to sunlight has not been measured in most of the studies on rickets. From the literature available, it would appear that there is a need for longitudinal research on the growth and development of alternatively fed infants and preschool children and for information on the nutrient composition of alternative foods.

The blood iron, vitamin B-12, and folate status of the 1985 birth cohort of Dutch infants aged 10.1-20.4 mo fed macrobiotic diets (n = 50) and matched omnivorous control infants (n = 57) was measured. Fe deficiency (combination of Hb less than 120 g/L, ferritin less than 12 micrograms/L, and FEP greater than 1.77 mumol/L) was observed in 15% of the macrobiotic group but not in the control group (p = 0.003). Plasma vitamin B-12 concentrations in the macrobiotic group were far below those of the control group (geometrical mean: 149 and 404 pmol/L, respectively, p less than 0.001). Plasma folate concentrations were higher in the macrobiotic group (31.6 +/- 11.7 nmol/L) than in the control group (21.1 +/- 8.8 nmol/L, p less than 0.001). In the macrobiotic group mean corpuscular volume, mean corpuscular hemoglobin mass, and mean corpuscular hemoglobin concentration were higher and hematocrit and red blood cells were lower (all p less than 0.05) than in the control group. It is advised to incorporate regular servings of animal foods into the macrobiotic diet to obtain an adequate amount of vitamin B-12.

A mixed-longitudinal study was carried out in the 1985 Dutch birth cohort of macrobiotic infants aged 4-18 months (n = 53) and 57 omnivorous control infants matched for month of birth, sex, parity, educational level of the father and the residential area. Study methods included regular anthropometric measurements and a psychomotor testing. Reported birth weight was 180 g lower in the macrobiotic group than in the control group and was positively associated with maternal weight increase during pregnancy. Between 4 and 18 months of age, mean values for all anthropometric parameters were considerably lower in the macrobiotic infants. From birth to 4 months, weight gain was less in macrobiotic infants, and from 6 months the rate of growth in weight and length decreased further, reaching its lowest value between 8 and 14 months of age. A similar pattern was also observed for other anthropometric parameters. Between 8 and 14 months, arm circumference showed an absolute decrease. During this period, increase in arm muscle mass in the macrobiotic group was only half of that in the control group. From 14 months of age, growth stabilized parallel to the 10th percentile of the Dutch references. Gross motor and language development were also slower in the macrobiotic infants. The paediatrician observed major wasting of skin and muscles in 30 per cent of them. The growth rate for weight and arm circumference was independently associated with the energy intake and the protein content of the macrobiotic diet. Growth in length was positively associated with protein content of the diet, but not with energy intake.

Information on food intake during weaning was collected as part of a mixed-longitudinal study on the nutritional status and growth of the 1985 Dutch birth cohort of infants on macrobiotic diets (n = 53) and a matched control group on omnivorous diets (m = 57). Weighed food records over 3d, including breast-milk, were obtained on 49 macrobiotic and 57 control infants at 2-monthly intervals between the ages of 6 and 16 months. Intake of energy and nutrients was calculated using the Dutch food composition table which was supplemented by our own analyses of 50 macrobiotic foods. Ninety-six per cent of the macrobiotic infants and 74 per cent of the control infants had been breast-fed, but breast-feeding continued longer in the macrobiotic group (13.6 vs 6.6 months, P less than 0.001). In the macrobiotic group, complementary feeding started at 4.8 months with water-based cereal porridges, followed later by vegetables, sesame seeds and pulses. Fruits were rarely given and products of animal origin were avoided. For all age groups combined, the intake of energy, protein, fat, calcium, riboflavin and vitamin B12 was significantly lower in the macrobiotic infants, whereas their intake of polysaccharides, fibre, iron and thiamin was higher than that of the control infants. The macrobiotic weaning diet tended to be bulky with a low energy density (2.4 kJ/g, controls: 3.4 kJ/g, P less than 0.05) and a high fibre content. Protein intake of the macrobiotic infants was only 80 per cent of the Dutch recommended daily intakes at the age of 6-8 months, and at 8 months, 69 per cent of this was derived from plant sources. Calcium intake was 280 mg/d; correction for calcium derived from hard tap-water raised the calcium intake to 308 mg in the macrobiotic age group of 14 months. The evidence of biochemical deficiencies of iron, riboflavin, vitamin B12, vitamin D and calcium is discussed. It is suggested that the macrobiotic diet should be supplemented with fat, fatty fish and dairy products.