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Low phosphorus status might contribute to the onset of obesity

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Overweight and obesity are becoming global health problems. Although genetics certainly plays a role, weight gain is ultimately the result of a failure in the balance between energy expenditure and energy intake. Obesity during the past few decades was paralleled with several changes in dietary habits favouring low phosphorus consumption. This is believed to compromise adenosine triphosphate (ATP) production that is involved in the regulation of energy metabolism. Ingestion of high‐carbohydrate–low phosphorus food is known to increase insulin release, to simultaneously stimulate peripheral uptake of phosphorus and the phosphorylation of many compounds. This creates a competition for phosphorus that compromises its availability for ATP production, possibly translated into low diet‐induced thermogenesis. Moreover, reduced hepatic ATP production is believed to be transmitted through neural afferents to the central nervous system, resulting in an increase in food intake. On the other hand, the positive relation between phosphorus and red blood cell 2,3‐diphosphoglycerate, which reduces oxygen affinity to haemoglobin, would be expected to reduce the capacity for physical activity. In line with that, plasma phosphorus status was reported to be inversely related to body weight. Adequate intakes of phosphorus are thus potentially protective against rising obesity epidemic across the globe.
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Etiology and Pathophysiology
Low phosphorus status might contribute to the onset
of obesity
O. A. Obeid
Department of Nutrition and Food Science,
Faculty of Agricultural and Food Sciences,
American University of Beirut. Beirut, Lebanon
Received 15 January 2013; revised 8 March
2013; accepted 22 March 2013
Address for correspondence: Professor OA
Obeid, Department of Nutrition and Food
Science, Faculty of Agricultural and Food
Sciences, American University of Beirut,
Beirut 1107 2020, PO Box 11-0236, Lebanon.
E-mail: omar.obeid@aub.edu.lb
Summary
Overweight and obesity are becoming global health problems. Although genetics
certainly plays a role, weight gain is ultimately the result of a failure in the balance
between energy expenditure and energy intake. Obesity during the past few
decades was paralleled with several changes in dietary habits favouring low
phosphorus consumption. This is believed to compromise adenosine triphosphate
(ATP) production that is involved in the regulation of energy metabolism. Inges-
tion of high-carbohydrate–low phosphorus food is known to increase insulin
release, to simultaneously stimulate peripheral uptake of phosphorus and the
phosphorylation of many compounds. This creates a competition for phosphorus
that compromises its availability for ATP production, possibly translated into
low diet-induced thermogenesis. Moreover, reduced hepatic ATP production is
believed to be transmitted through neural afferents to the central nervous system,
resulting in an increase in food intake. On the other hand, the positive relation
between phosphorus and red blood cell 2,3-diphosphoglycerate, which reduces
oxygen affinity to haemoglobin, would be expected to reduce the capacity for
physical activity. In line with that, plasma phosphorus status was reported to be
inversely related to body weight. Adequate intakes of phosphorus are thus poten-
tially protective against rising obesity epidemic across the globe.
Keywords: ATP, obesity, phosphorus.
obesity reviews (2013) 14, 659–664
Introduction
Obesity and increased body adiposity are rapidly emerging
global health problems (1–4). While genetics certainly plays
a role, weight gain is ultimately the result of a failure to
balance energy expenditure and energy intake (food
intake). Overweight and obesity are spread in both high-
and low-income countries and are associated with urbani-
zation and westernization of diets, especially among low-
income urban groups (2). The increases in obesity during
the past few decades have paralleled modernization (indus-
trialization, globalization of food markets, etc.) and several
changes in dietary habits. These are mainly related to the
dramatic increase in the consumption of refined cereals
(where refinement reduces phosphorus content by about
70%) and oils, sugars, and sweeteners such as high fructose
corn syrup (HFCS) which contain negligible amounts of
phosphorus (1–4). These commodities contribute to more
than 50% of the food supply (kcal/capita/day) in most
countries (5), not including the contribution of starchy
foods (e.g. potatoes) that are also low in phosphorus. The
contribution of low phosphorus commodities to total
energy intake is known to be inversely related to income,
especially among urban populations (2). On the other
hand, phosphorus content of major raw (non-refined)
foods (e.g. cereals, pulses, meat) is around 1 mg P/kcal. It
can be predicted that a person consuming a diet of mainly
raw, unprocessed foods with a 2,500 kcal daily energy
obesity reviews doi: 10.1111/obr.12039
659© 2013 The Author
obesity reviews © 2013 International Association for the Study of Obesity 14, 659–664, August 2013
intake would consume about 2.5 g of phosphorus, which is
lower than the 4 g d-1upper limit of intake (6). Such a diet
is believed to have been consumed by our ancestors before
the industrial advancement. Current daily phosphorus
intake is about 1.4 g d-1(7), although concern has been
raised regarding the contribution of phosphorus containing
additives, cola beverages (~16 mg/100 mL), etc., as well as
the bioavailability of phosphorus from different sources
(8). This intake is lower than the predicted intake when
consuming a diet with 1 mg P/kcal, but is above the present
recommended daily allowance (RDA) of 700 mg. It should
be mentioned that RDA is based on the lower end of the
normal adult serum inorganic phosphate (Pi) and that this
would have been 2,100 mg if it had been based on the
middle of the normal range (6). On the other hand, food
habits are known to vary according to socioeconomic
status, with high energy dense-nutrient poor foods highly
consumed by people of low socioeconomic status, mainly
because of their high energy density (kcal g-1food) and
low energy cost ($US0.1–$US1/1,000 kcal) (1–4,9). Such
dietary habits were proposed to be one factor behind the
high prevalence of obesity among people of low socioeco-
nomic status (9), and this may implicate phosphorus in this
process due to the fact that these foods are known to be low
in phosphorus. Thus, given the increased prevalence of
obesity among people consuming high quantities of food
containing low levels of phosphorus, it is reasonable to
postulate that low phosphorus intake may be involved in
the development of obesity.
Phosphorus, adenosine triphosphate and
energy balance
The production of adenosine triphosphate (ATP), including
hepatic ATP, depends upon adequate sources of phospho-
rus (P) (10,11), and this is coupled with two other factors.
First, only limited quantities of free phosphate are stored
within cells, and most tissues depend upon extracellular
fluid (ECF) Pifor their metabolic phosphate, and under low
ECF Pilevels, cellular dysfunction follows. Second, there is
virtually constant fractional phosphorus absorption across
a broad range of intakes (6), suggesting a lack of an adap-
tive mechanism that improves phosphorus absorption at
low intakes, as can occur with some other micronutrients.
Therefore, phosphorus availability in food becomes an
important factor that governs phosphorus levels in the
circulation and in turn its availability for ATP production.
Thus, low phosphorus intake would be expected to reduce
ATP production, which is believed to affect food intake and
energy expenditure.
The physiological regulation of food intake, which acts
principally at the central level, is believed to be partially
governed by signals originating from the liver via the
hepatic postprandial metabolism involving ATP production
(12,13). Evidence supports a relationship between declin-
ing hepatic ATP levels and increasing food intake; this
decline is thought to transduce changes in hepatic energy
status into neural signals or hepatic vagal afferent activity
that is transmitted to the central nervous system (12–17).
Moreover, there are controversial data on the difference in
diet-induced thermogenesis (DIT) between lean and obese
subjects (18–23), with a large number of studies showing
reduced DIT in obesity (19–23), that seems to be normal-
ized upon losing weight (22,23), indicating that DIT is not
a causal factor for obesity. However, reduced DIT of dia-
betic as compared to non-diabetic obese subjects (24) may
implicate insulin in this process (25). The reduction in DIT
of obese diabetic subjects, with both increased and reduced
insulin response (24), implies that this reduction is not
related to insulin per se, but rather to its function. Insulin
resistance is known to be inversely related to peripheral
uptake of glucose (impaired glucose tolerance) and phos-
phorus, implicating the latter in this process, especially that
peripheral uptake is known to be reduced with the progres-
sion of insulin resistance to impaired glucose tolerance and
diabetes (26).
In addition, plasma phosphorus is known to be posi-
tively related to red blood cell (RBC) ATP and 2,3 diphos-
phoglycerate (2,3-DPG) concentration, which is known
to decrease the oxygen affinity to haemoglobin (27–31).
Reduced 2,3-DPG would be expected to decrease oxygen
availability for oxidation, which in turn would contribute
to lowering the capacity for physical activity resulting in a
reduction in energy expenditure.
Thus, it is the hypothesis that low phosphorus status may
contribute to the development of obesity through its role in
the regulation of food intake, thermogenesis and capacity
for physical activity. (Fig. 1).
Dietary habits, phosphorus and body weight
Several dietary factors are known to compromise phospho-
rus availability for ATP production. Ingestion of a high
carbohydrate-low phosphorus meal is known to induce a
marked reduction in plasma Pistatus (32–34) mainly due to
the stimulation of insulin release, which is known to
increase phosphorus uptake by peripheral tissues (mainly
muscles) (35) and phosphorylation of many compounds
(e.g. protein, carbohydrate, etc.). This creates competition
for phosphorus between ATP production and the phospho-
rylation of other compounds.
Fructose is known to have a ‘phosphate-sequestering’
capacity, where fructose 1-phosphate accumulates in the
liver because, unlike for glucose, there is no feedback
mechanism for fructose phosphorylation. This makes
phosphorus unavailable to participate in other essential
metabolic reactions, including the regeneration of ATP
(10,15,36,37). Therefore, under high fructose or high
660 Phosphorus and obesity O. A. Obeid obesity reviews
© 2013 The Author
obesity reviews © 2013 International Association for the Study of Obesity14, 659–664, August 2013
glucose/low phosphorus conditions, competition for phos-
phorus occurs between ATP production and phosphoryla-
tion of other compounds.
Studies looking at the relation between phosphorus
intake and body weight have reported conflicting findings
(38,39). While those looking at serum phosphate were
consistently reported to be inversely related to body weight
(40–49) (Table 1), hypophosphatemia was proposed to be
involved in the development of the metabolic syndrome,
including increased body mass index (BMI) (50). The simi-
larity in phosphate fractional excretion rate between lean,
overweight and obese subjects implied that the reduction in
serum phosphate was mainly attributed to a reduction in
dietary intake rather than to problems with excretion (42).
It is therefore possible to suggest that phosphorus is
involved in the regulation of body weight.
Many studies are in support of a role for phosphorus or
hepatic ATP in the regulation of body weight and food
intake. Several abnormalities in hepatic ATP were reported
in animal and human experiments on obesity (50–52). In
humans, liver ATP status was reported to be affected by
fructose consumption (53) and infusion (51). In addition,
hepatic ATP stores (52) and recovery from hepatic ATP
depletion (using fructose infusion) (51) were inversely
related to BMI. Moreover, an analysis of metabolic data
using the Knowledge Discovery in Databases concluded
that ATP deficiency or decreased energy levels were
strongly linked to the development and sustenance of
obesity by driving overeating and conserving energy (54).
Thus, human studies indirectly support a potential role for
hepatic ATP in energy and body weight regulations (52,53).
In line with that, we have recently found that the addition
of 500 mg P to different carbohydrate preloads caused a
substantial reduction in ad libitum subsequent energy
intake (27–33%) (55).
There is also evidence in support of phosphorus involve-
ment in thermogenesis. Addition of phosphorus to orange
juice was reported to increase postprandial thermogenesis
of obese but not lean subjects (56,57), and phosphorus
supplementation of obese subjects, in a weight reducing
program, was shown to increase resting metabolic rate
(58,59). It is thus believed that phosphorus supplementa-
tion may have exerted its effect through an increase in
peripheral phosphorus (as well as glucose) uptake, espe-
cially that P is known to stimulate insulin sensitivity
(26,40,60). Pointing to the capacity of P for inducing
physical activity, there are limited and inconsistent data on
RBC 2,3-DPG concentration of obese subjects (57,61,62).
Nevertheless, the magnitude of increase in RBC 2,3-DPG
concentration following phosphate loading (27,30,57) was
reported to be higher in obese as compared to lean subjects,
and this was accompanied with higher energy expenditure
in the former (57). Along the same lines, obesity was
reported to be associated with chronic fatigue syndrome
(63) and physical fatigue (64), and phosphate loading (up
to4gd
-1) has been used for different durations to improve
physical performance (65).
Discussion
Phosphorus may provide a link between different observa-
tions associated with increased body weight or energy
intake. The phosphate-sequestering capacity of fructose
may be involved in the synergetic relation between HFCS
intake and obesity (66). The high phosphorus content of
protein may be implicated in the reduction of energy intake
under conditions of increased protein intake (67,68), as
well as in the decrease in body weight and fat mass under
an isocalorically high-protein diet (69). In addition, the
high phosphorus content of milk may partially explain the
inverse association between dairy product intake and body
weight, especially given that calcium failed to clarify such
an association (70–72). In fact, increased calcium intake
from both diet and supplements is known to reduce phos-
phorus absorption (73), and calcium carbonate in high
doses is used as phosphate binder. Moreover, the inverse
relationship between increased intake of whole grains and
the risk of the different components of metabolic syndrome
(74,75) may be partially explained by their richness in
phosphorus, as added cereal fibre failed to induce such an
Hyperphagia
High CHO-Low P
High Insulin release
Increased P uptake and phosphorylation
Liver Muscle
Low hepatic ATP production Low ATP production
Low thermogenesis
Increased efficiency of weight gain
Competition for phosphorus
Weight gain Obesity
Figure 1 Proposed interaction among phosphorus, adenosine
triphosphate (ATP) production and obesity.
obesity reviews Phosphorus and obesity O. A. Obeid 661
© 2013 The Author
obesity reviews © 2013 International Association for the Study of Obesity 14, 659–664, August 2013
effect and was proposed to be a marker of other compo-
nents of whole grains that impart health advantages (76).
On the other hand, the ability of phosphate depletion to
simulate glucose intolerance, probably through the stimu-
lation of hepatic glucose production and reduced insulin
level (77) that requires ATP for its release by pancreatic
b-cells (78), is supported by several observations. For
example, increased serum phosphate and phosphorus
intake of non-diabetic subjects were reported to be syner-
gistically related to improvement in glucose tolerance
(32,40) and insulin sensitivity (26,32,40,47,60). Thus,
reduced phosphorus status would favour the development
of obesity, as postprandial glycaemia is known to be impli-
cated in the development of chronic metabolic diseases
such as obesity, type 2 diabetes mellitus and cardiovascular
disease (79). Such a process can be further aggravated
by the development of obesity that is characterized by
insulin resistance, which predisposes to the development
of impaired glucose tolerance that is known to decrease
peripheral uptake of both glucose and phosphorus (26),
therefore reducing the capacity of ATP synthesis that would
be translated into a reduction in thermogenesis (26,80).
In summary, ATP production, which is dependent on
phosphorus availability, is essential for many processes
including eating behaviour and energy expenditure.
Increased consumption of refined cereals, potatoes, sugars
(fructose) and oils, which are characteristics of the modern
diet, would negatively impact phosphorus availability.
Insulin release stimulates the phosphorylation of many
compounds and this may compromise phosphorus avail-
ability for ATP production, especially given that ATP seems
to act as a phosphate donor (37). Thus, increased insulin
release under low phosphorus diet exacerbates the situa-
tion. Moreover, reduced phosphorus peripheral uptake due
to impaired glucose tolerance was postulated to affect ther-
mogenesis (26,80). It is also reasonable to postulate that
boosting the status of phosphorus in food would amelio-
rate such metabolic changes. This can be accomplished by
fortification (e.g. white flour) and/or the establishment of a
carbohydrate to phosphorus ratio comparable to that of
carbohydrate to thiamine or energy to thiamine.
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664 Phosphorus and obesity O. A. Obeid obesity reviews
© 2013 The Author
obesity reviews © 2013 International Association for the Study of Obesity14, 659–664, August 2013
... Suppressing elevated parathormone increases the reabsorption of phosphate from the proximal tubules of the kidney, thereby preventing urinary wasting of phosphorous [12]. Due to its widespread distribution and important role in vital cellular processes such as adenosine triphosphate production (ATP), insufficient phosphorus levels may promote muscle weakness, impaired leukocyte function [13], and obesity [14]. ...
... However, the industrialization and globalization of food markets has caused several changes in dietary habits. The dramatic increase in the consumption of refined cereals, oils, sugars, and sweeteners has caused a decrease in daily phosphorus ingestion [14,28]. These changes have occurred in parallel with increase in obesity [29]. ...
... It has been hypothesized that low phosphorus levels may contribute to the development of obesity through its role in the regulation of food intake and thermogenesis. Additionally, phosphorus has the capacity for inducing physical activity [14]. Phosphorus supplementation in obese subjects in a weight-reducing program resulted in an increase in resting metabolic rate [30,31]. ...
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Abstract Background To evaluate the association of vitamin D and thyroid-stimulating hormone (TSH) with weight loss (WL) percentage (%) in patients with diabetes/prediabetes and Class II/III obesity. Methods A retrospective cohort study was designed. Data were collected from a database of a referral endocrinology clinic that is prospectively and systematically generated. After exclusion of unavailable cases, the study enrolled 285 patients (51 ± 11 years old, female/male = 208/77; diabetes/prediabetes = 159/126; no/on levothyroxine replacement = 176/109; Class II/III obesity = 184/101, respectively) who maintained euthyroidism and were followed up for ≥6 months. The data were analyzed to determine the predictors of WL%. Results Compared with baseline, in the median 22 months of follow-up, the whole study group lost 5.1% of their baseline body weight. As most obesity management trials define success as ‘at least 10% of WL compared to baseline’, we stratified the patients based on WL% extents. The distribution was as follow: Group 1 (n = 61) lost ≥10% body weight, Group 2 (n = 162) lost
... Secondly, low phosphorus intake limits phosphorus availability for adenosine triphosphate (ATP) synthesis. The signal of declined hepatic ATP production is transmitted to the central nervous system, leading to hyperphagia and increased food consumption [36]. Thirdly, low ATP production causes deficiency in thermogenesis and subsequently increases efficiency in weight gain [36]. ...
... The signal of declined hepatic ATP production is transmitted to the central nervous system, leading to hyperphagia and increased food consumption [36]. Thirdly, low ATP production causes deficiency in thermogenesis and subsequently increases efficiency in weight gain [36]. Fourthly, low serum phosphorus is associated with reduced 2,3-diphosphoglycerate level, a compound that has a strong affinity towards deoxygenated haemoglobin. ...
... Fourthly, low serum phosphorus is associated with reduced 2,3-diphosphoglycerate level, a compound that has a strong affinity towards deoxygenated haemoglobin. Reduced interaction between 2,3-diphosphoglycerate and haemoglobin increases the oxygen affinity towards haemoglobin, thus lowering the oxygen availability for oxidation, capacity for physical activity, and energy expenditure [36]. a compound that has a strong affinity towards deoxygenated haemoglobin. ...
Article
Phosphorus, present as phosphate in biological systems, is an essential mineral for various biological activities and biochemical processes. Numerous studies have indicated that disturbed phosphate balance may contribute to the development of metabolic syndrome (MetS). However, no consistent result was found on the association between phosphorus intake and serum phosphate concentration with MetS. It is believed that both positive and negative impacts of phosphorus/phosphate co-exist in parallel during MetS condition. Reduced phosphate level contributed to the development of obesity and hyperglycaemia. Low phosphate is believed to compromise energy production, reduce exercise capacity, increase food ingestion, and impair glucose metabolism. On the other hand, the effects of phosphorus/phosphate on hypertension are rather complex depending on the source of phosphorus and subjects' health conditions. Phosphorus excess activates sympathetic nervous system, renin-angiotensin-aldosterone system, and induces hormonal changes under pathological conditions, contributing to the blood pressure-rising effects. For lipid metabolism, adequate phosphate content ensures a balanced lipid profile through regulation of fatty acid biosynthesis, oxidation, and bile acid excretion. In conclusion, phosphate metabolism serves as a potential key feature for the development and progression of MetS. Dietary phosphorus and serum phosphate level should be under close monitoring for the management of MetS.
... Finally, we observed a significant reduction in serum phosphate concentration in children with obesity. This is in line with observations in adult obese populations, but it has not been studied extensively in pediatric patients [88,89]. Phosphorus availability modulates adenosine triphosphate (ATP) production. ...
... Phosphorus availability modulates adenosine triphosphate (ATP) production. In patients with obesity, two main factors contribute to decreased availability of phosphorus; firstly, 'western' dietary patterns, including high consumption of refined cereals, potatoes, fructose, and oils, all of which negatively impact phosphorus availability; secondly, insulin resistance, one of the most common consequences of obesity, characterized by increased insulin release, which in turn stimulates the phosphorylation of many compounds and limits phosphorus availability for ATP production, exacerbating the effects of low phosphorus availability caused by diet [88]. Thus, in our study, the decreased concentration of phosphate might indicate the early stages of insulin resistance development in obese children. ...
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Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography–mass spectrometry (GC–MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC–MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.
... In the literature, a link between phosphate and adipose tissues is rarely reported, either in extra-or intra-medullar adipose tissues. In humans, an inverse correlation between serum Pi levels and obesity has been observed, and an association between high phosphate diet and the suppression of lipogenesis in white adipose tissue has been described both in humans and rodents (50)(51)(52)(53)(54)(55)(56)(57). Interestingly, acute phosphate restriction in mice decreases bone formation and results in an increase in BMAT due to defects in the commitment of BMSC preferentially towards the adipogenic lineage involving the Wnt signaling pathway (58,59). ...
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The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in PiT2-/- mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although PiT2-/- mice have higher BMAT volume than control PiT2+/+ mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old PiT2-/- compared to PiT2+/+ mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify SLC20a2/PiT2 as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs.
... Studies have reported that low consumption of phosphorus (<2.5 g/day) is positively associated with increased body weight. 95,96 Another study reported that phosphorus supplementation (375 mg in every main meal, for 12 weeks) and dietary magnesium (10 mg per 1000 kcal/day, for eight months) halted weight gain and BMI growth while significantly decreasing waist circumference in healthy and obese participants, thus suggesting that phosphorus supplementation and magnesium have the potential to prevent obesity. 95,97 Antioxidant Properties ...
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Honey has a long history of therapeutic properties for multiple diseases, including inflammation and oxidative stress. This review aimed to provide a better understanding and renewed interest in the potential role of honey in obesity control, obesity-related diseases treatment and weight management, with specific reference to its components and the effect of honey overall. There is compelling evidence that honey possesses the desired properties for this purpose, as seen in the in vitro, in silico, in vivo and clinical analyses discussed in this review. This review also highlights the components potentially responsible for the health benefits of honey. Honey and its components reduce blood sugar levels, improve insulin sensitivity and lipid metabolism by reducing triglycerides, and reduce total cholesterol and LDL levels while increasing HDL levels that prevent excessive weight gain and reduce the risk of obesity and its complications. Further controlled studies are necessary to validate the role of honey in the management of obesity, both as a preventive and as a therapeutic agent.
... Obeid argued that reduction in intracellular phosphate availability causes low thermogenesis secondary to reduced ATP production. 35 Thermogenesis has been shown to affect weight control, with low thermogenesis associated with greater predisposition to gain weight. 36 This is possibly due to the effects of low thermogenesis on hunger and appetite. ...
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Purpose: This study aimed to investigate the association between sex-specific baseline serum phosphate and the incidence of new-onset cardiometabolic disease in a cohort of Shanghai-based older Chinese individuals. Patients and methods: A community cohort of 5000 disease-free Chinese men and women was recruited in 2013 and followed until 2017 for the development of cardiometabolic disease. Participants underwent index and follow-up health screens at the Tongji Medical School affiliated Shanghai East Hospital, including blood biochemistry analysis, anthropometric measurements, interview on health-related behaviors, and clinical evaluation. Results: Higher baseline serum phosphate (>1.25 mmol/L) was significantly associated with new-onset type-2 diabetes mellitus (HR 1.730, 95% CI 1.127-2.655) and metabolic syndrome (HR 0.640, 95% CI 1.085-2.155) in women. Baseline serum phosphate was associated with age, BMI, waist circumference, SBP, total calcium, bicarbonate, and total cholesterol in women. The estimated risk of developing diabetes mellitus in women with inorganic phosphate >1.25 mmol/L was 14.54%. Inorganic phosphate accounted for 9.2% of the variance explained in a total estimated 14.52% of variance attributed to BMI, total cholesterol, total calcium, waist circumference, and inorganic phosphate. Conclusion: Serum phosphate concentration showed sex-specific associations with diabetes and metabolic syndrome. Higher inorganic phosphate was associated with increased risk of developing diabetes mellitus in women. These findings may be important in the assessment of individualized metabolic risk.
... 19,20 Regarding phosphate, two studies have described positive associations between a low phosphorus status and a higher risk for incident obesity. 21,22 Our results showed decreased levels of α-hydroxycaproate (Sup. Table 1) and 1-palmitoyl-2-stearoyl-GPC in the group given the pasteurized A. muciniphila. ...
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Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced β-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.
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Background: Although vitamin D deficiency has been studied in various populations, there are few data on its prevalence and associated factors among Moroccan women. Aim: To determine the prevalence of vitamin D deficiency and investigate its association with body mass index (BMI), waist circumference, and serum concentrations of parathyroid hormone, calcium, and phosphorus in a sample of Moroccan adult women. Methods: This is a cross-sectional study conducted at Mohammed V Military Hospital of Instruction, Rabat. Anthropometric measurements and biochemical analyses were performed using standard procedures Results: A total of 714 women aged 18–65 years participated in this study. The overall prevalence of vitamin D deficiency was 74.4%. Approximately 24% and 51% of women had severe and moderate vitamin D deficiency, respectively. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were inversely correlated with BMI in vitamin D-deficient subjects ( P = 0.036) and with parathyroid hormone 1–84 (PTH1-84) levels in the study sample ( P = 0.010). PTH1-84 concentrations were greater among overweight/obese individuals compared to their non-overweight peers ( P = 0.001) and tended to be higher among vitamin D-deficient women than vitamin D-sufficient women ( P = 0.053). Conclusion: This study showed a very high prevalence of vitamin D deficiency in this sample of Moroccan women. Lower serum 25(OH)D levels were associated with increased BMI in vitamin D-deficient women and with elevated PTH1-84 levels among the study sample. Although these findings come from a convenience sample of women that attended a nutrition clinic, they underscore the urgent need to develop public health interventions to improve women’s vitamin D status.
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Minerals are critical for maintaining overall health. These tiny chemical compounds are responsible for enzymatic activation, maintaining healthy teeth and bones, regulating energy metabolism, enhancing immunity and aiding muscle and brain function. However, mineral deficiency in the form of inadequate or under nourished intake affects millions of people throughout the world, with well-documented adverse health consequences of malnutrition. Conversely, mineral deficiency may also be a risk factor for insulin resistance (IR) and obesity. This review focuses on another, more “less discussed” form of malnutrition, namely mineral deficiency and its contribution to metabolic disorders. At the cellular level, minerals maintain not only molecular communication but also trigger several key biochemical pathways. Disturbances in these processes due to mineral insufficiency may gradually lead to metabolic disorders such as insulin resistance, pre-diabetes and central obesity which might lead to renal failure, cardiac arrest, hepatic carcinoma and various neurodegenerative diseases. Here we discuss the burden of disease promoted by mineral deficiencies and the medical, social and economic consequences. Mineral deficiency-mediated IR and obesity have a considerable negative impact on individual well-being and physical consideration and economic productivity. We discuss possible molecular mechanisms of mineral deficiency that may lead to IR and obesity and suggest strategies to counter these metabolic disorders. To protect mankind from mineral nutrient deficiencies, the key is to take a variety of foods in reasonable quantities, such as organic and pasture-raised eggs, low fat dairy, and grass-fed and finished meats, insecticide and pesticide-free vegetables and fruits.
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Objective Few epidemiological studies have investigated the associations between calcium, magnesium, and phosphorus intake and pancreatic cancer. We examined these associations in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods Diet was assessed using the Dietary Questionnaire (DQX) at baseline in the intervention arm and the Dietary History Questionnaire (DHQ) in 1999 or around the third anniversary of randomization in both the intervention and control arms. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer occurred from 58,477 participants who completed DQX; 380 cases arose from 101,622 participants who responded to DHQ over a median follow-up of 8.9 years. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Total calcium intake was inversely associated with pancreatic cancer [HR (95% CI) for the fourth vs. the first quartiles in the DHQ cohort: 0.67 (0.47, 0.96); p-trend: 0.035]. An inverse association was also observed for total magnesium intake [HR (95% CI) for the fourth vs. the first quartiles in the DQX cohort: 0.61 (0.37, 1.00); p-trend: 0.023]. Reduced risk associated with total calcium intake was confined to subjects with a high fat intake (>73 g/day) in the DHQ cohort (p-interaction: 0.16). Conclusions There was not a significant association between dietary phosphorus intake and pancreatic cancer risk in both cohorts. Total intake of calcium and magnesium are associated with a lower pancreatic cancer risk. The effect of total calcium intake was modified by fat intake.
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Global energy imbalances and related obesity levels are rapidly increasing. The world is rapidly shifting from a dietary period in which the higher-income countries are dominated by patterns of degenerative diseases (whereas the lower- and middle-income countries are dominated by receding famine) to one in which the world is increasingly being dominated by degenerative diseases. This article documents the high levels of overweight and obesity found across higher- and lower-income countries and the global shift of this burden toward the poor and toward urban and rural populations. Dietary changes appear to be shifting universally toward a diet dominated by higher intakes of animal and partially hydrogenated fats and lower intakes of fiber. Activity patterns at work, at leisure, during travel, and in the home are equally shifting rapidly toward reduced energy expenditure. Large-scale decreases in food prices (eg, beef prices) have increased access to supermarkets, and the urbanization of both urban and rural areas is a key underlying factor. Limited documentation of the extent of the increased effects of the fast food and bottled soft drink industries on this nutrition shift is available, but some examples of the heterogeneity of the underlying changes are presented. The challenge to global health is clear.
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Phosphate infusion under euglycemic conditions have been reported to influence insulin sensitivity, with an increased rate of glucose disposal (1). While hypophosphatemia was found to be associated with insulin insensitivity and impaired glucose tolerance (2). It was also reported that healthy non-diabetic individuals with low serum phosphate levels tend to have elevated blood glucose levels and reduced insulin sensitivity in the 2 h postprandial period (3). The rise in insulin levels is known to reduce serum phosphate due to the shift of extracellular phosphate to the intracellular region. In view of the increased intake poor dietary P (refined cereals, sugar and sweeteners), it became questionable whether phosphate can affect the postprandial glycaemia. The objectives of the study were to determine the effect of phosphate on postprandial glycaemia, insulinemia and insulin sensitivity in an oral glucose tolerance test (OGTT). Eight healthy male subjects of normal BMI were recruited. Each subject was exposed in random order to two experimental solutions: (1) glucose solution containing 75 g glucose; (2) glucose and phosphate solution, containing 75 g glucose and 500 mg P. Blood samples were collected at fasting, and after drinking the solutions at 15, 30, 60, 90, 120, 180 and 240 min. Serum insulin, glucose, total phosphate and inorganic phosphate were measured. Homoeostatic model assessment (HOMA) was calculated to determine insulin sensitivity.
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Background: It is currently unclear whether altering the carbohydrate-to-protein ratio of low-fat, energy-restricted diets augments weight loss and cardiometabolic risk markers. Objective: The objective was to conduct a systematic review and meta-analysis of studies that compared energy-restricted, isocaloric, high-protein, low-fat (HP) diets with standard-protein, low-fat (SP) diets on weight loss, body composition, resting energy expenditure (REE), satiety and appetite, and cardiometabolic risk factors. Design: Systematic searches were conducted by using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials to identify weight-loss trials that compared isocalorically prescribed diets matched for fat intake but that differed in protein and carbohydrate intakes in participants aged ≥18 y. Twenty-four trials that included 1063 individuals satisfied the inclusion criteria. Results: Mean (±SD) diet duration was 12.1 ± 9.3 wk. Compared with an SP diet, an HP diet produced more favorable changes in weighted mean differences for reductions in body weight (−0.79 kg; 95% CI: −1.50, −0.08 kg), fat mass (FM; −0.87 kg; 95% CI: −1.26, −0.48 kg), and triglycerides (−0.23 mmol/L; 95% CI: −0.33, −0.12 mmol/L) and mitigation of reductions in fat-free mass (FFM; 0.43 kg; 95% CI: 0.09, 0.78 kg) and REE (595.5 kJ/d; 95% CI: 67.0, 1124.1 kJ/d). Changes in fasting plasma glucose, fasting insulin, blood pressure, and total, LDL, and HDL cholesterol were similar across dietary treatments (P ≥ 0.20). Greater satiety with HP was reported in 3 of 5 studies. Conclusion: Compared with an energy-restricted SP diet, an isocalorically prescribed HP diet provides modest benefits for reductions in body weight, FM, and triglycerides and for mitigating reductions in FFM and REE.
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Understanding energy and macronutrient metabolism is critical to the understanding of obesity, especially etiology, relationship between genetic and environmental influences, and approaches to prevention and treatment. The importance of fat balance to obesity is emphasized, and this is first established by an analysis of energy and macronutrient balance based on known human physiology and then backed up by clinical studies. The known metabolic risk factors for body weight gain are briefly summarized, and the emerging pattern of their relationships with weight gain is described. The metabolic responses to weight loss are also examined, along with the question of possible metabolic adaptation to a hypocaloric diet. Since the fat balance concept has major implications for the prevention and treatment of obesity, some overall directions for these areas are presented.
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A marked reduction in red cell glucose utilization, lactate production, and 2,3-diphosphoglycerate and adenosine triphosphate concentration occurred in a patient with intractable diarrhea during a period of hypophosphatemia induced by parenteral nutrition with hypertonic glucose and protein hydrolysate. During the period of hypophosphatemia the patient's hemoglobin had an increased affinity for oxygen. Restoration of plasma phosphate to normal in vivo or in vitro corrected the metabolic abnormalities of the patient's erythrocytes. During normophosphatemia hemoglobin-oxygen affinity was decreased in keeping with the increase in red cell organic phosphates associated with anemia. Therefore, severe hypophosphatemia in man can produce significant limitations on red cell metabolism, resulting in a curtailment of glycolysis, reduction of organic phosphates, and an inefficient relationship between hemoglobin and oxygen. Tissue oxygen delivery could be impaired under such circumstances. Furthermore, adenosine triphosphate levels can reach concentrations that threaten the survival of the red cell. These observations also provide support for the critical role of extracellular inorganic phosphate concentration in the maintenance and modulation of red cell metabolism in vivo.
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Objective Although obesity-associated fatty liver disease is emerging as one of the most common diseases in hepatology practice, it is unclear why liver disease prevalence increases with obesity. Because impaired energy homeostasis enhances the susceptibility of hepatocytes to injury, the aim of this study was to determine whether increased body mass index (BMI) is associated with decreased basal hepatic adenosine triphosphate (ATP) stores or impaired recovery from fructose-induced hepatic ATP depletion.
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. Obesity is characterized by insulin resistance which predisposes to the development of impaired glucose tolerance. It is postulated that in addition to its role in carbohydrate metabolism, insulin is the mediator of feecling-related increases in thermogenesis (the thermic effect of food and dietary-induced thermogenesis). The development of insulin resistance and/or deficiency is postulated to result in a decrease in feecling-related, insulin-mediated thermogenesis. As a consequence of this thermogenic defect there is an increase in efficiency of weight gain which accelerates the development and facilitates the maintenance of the obese state. Abnormalities in the insulin axis are thus not only involved in the pathogenesis of the carbohydrate intolerance of obesity but are also proposed as having a central role in a dysregulation of energy balance which contributes to the pathogenesis of obesity.
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High serum phosphorus is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Dietary intake of phosphorus, a major determinant of serum phosphorus, seems to be systematically underestimated using the available software tools and generalized nutrient content databases. Several sources of dietary phosphorus including the addition of phosphorus ingredients in food processing, and phosphorus content of vitamin and mineral supplements and commonly used over-the-counter or prescription medications are not fully accounted for by the nutrient content databases and software programs in current clinical use or used in large population studies. In this review, we explore the many unknown sources of phosphorus in the food supply to identify all possible contributors to total phosphorus intake of Americans that have escaped inclusion in past intake estimates. Our goal is to help delineate areas for future interventions that will enable tighter control of dietary phosphorus intake, a critical factor to maintaining health and quality of life in CKD and dialysis patients.
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ABSTRACT Serum inorganic phosphate was determined in 752 men born in 1926. An inverse correlation was found between serum inorganic phosphate levels and body weight. Other parameters of possible relevance to this finding, such as serum calcium, serum albumin, serum γ-glutamyltransferase, and the occurrence of upper gastrointestinal disorders were analysed, and no correlations to the phosphate level were detected.