Children with sleep schedule irregularity or shorter sleep duration more prone to obesity

Posted on January 26, 2011 by Dr. Jonathan

Sleep disorders are well known to have metabolic consequences for adults, but what about children? A study just published in the journal Pediatrics suggests that suboptimal sleep timing and duration have adverse effects on the metabolism of children too that promote obesity and metabolic dysfunction. The authors state:

“The goal was to explore the effects of duration and regularity of sleep schedules on BMI [body mass index] and the impact on metabolic regulation in children.”

The examined the sleep patterns of 308 children ages 4 to 10 for associations with BMI; fasting glucose, insulin, lipids (blood fats), and hsCRP (high sensitivity C-reactive protein, a marker for vascular inflammation). Their data support the importance of sleep for the pediatric metabolism:

“For obese children, sleep duration was shorter and showed more variability on weekends, compared with school days. For overweight children, a mixed sleep pattern emerged. The presence of high variance in sleep duration or short sleep duration was more likely associated with altered insulin, low-density lipoprotein, and high-sensitivity C-reactive protein plasma levels. Children whose sleep patterns were at the lower end of sleep duration, particularly in the presence of irregular sleep schedules, exhibited the greatest health risk.”

The authors’ conclusion supports a public health effort to reduce obesity and metabolic dysfunction in children by promoting regular sleep schedules:

“…the combination of shorter sleep duration and more-variable sleep patterns was associated with adverse metabolic outcomes. Educational campaigns, aimed at families, regarding longer and more-regular sleep may promote decreases in obesity rates and may improve metabolic dysfunction trends in school-aged children.”

Which diet is better for keeping weight off?

Posted on November 29, 2010 by Dr. Jonathan

An international study just published in The New England Journal of Medicine provides the most robust evidence so far that a high protein + low glycemic index diet is best for weight maintenance. The authors observe:

“Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power.”

773 overweight adults from eight European countries who completed an initial low-calorie weight loss phase were randomized to follow one of five diets for weight maintenance: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. The diets were ‘ad libitum’, meaning they were allowed to eat freely within the constraints of their diet plan. What did the data show?

“…only the low-protein–high-glycemic-index diet was associated with subsequent significant weight regain. In an intention-to-treat analysis, the weight regain was 0.93 kg less in the groups assigned to a high-protein diet than in those assigned to a low-protein diet and 0.95 kg less in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet.”

Moreover, it seems that the high-protein and low-glycemic-index groups were more comfortable:

“Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein–high-glycemic-index group dropped out of the study.”

Thus the authors conclude:

“In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss.”

Coffee polyphenols may suppress body fat accumulation

Posted on November 14, 2010 by Dr. Jonathan

A research paper just published in the American Journal of Endocrinology and Metabolism adds to the list of potential benefits from coffee. The authors state:

“The prevalence of obesity is increasing globally, and obesity is a major risk factor for type 2 diabetes and cardiovascular disease. We investigated the effects of coffee polyphenols (CPP), which are abundant in coffee and consumed worldwide, on diet-induced body fat accumulation.”

They fed the animal subjects either a control diet, a high-fat diet, or a high-fat diet supplemented with 0.5% to 1.0% CPP for 2 to 15 weeks. What did the data show?

“Supplementation with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, and infiltration of macrophages [inflammatory white blood cells] into adipose tissues. Energy expenditure evaluated by indirect calorimetry was significantly increased in CPP-fed mice.”

The authors delineated the details of the genetic expression and molecular signaling elicited by coffee polyphenols, concluding:

“These findings indicate that CPP enhances energy metabolism and reduces lipogenesis by downregulating SREBP-1c and related molecules, which leads to the suppression of body fat accumulation.”

Quercitin as effective as resveratrol for inflammation with diabetes and obesity

Posted on October 27, 2010 by Dr. Jonathan

There has been a lot of interesting science, some of it reported here, documenting the benefits of resveratrol for factors contributing to inflammation, insulin resistance, obesity, diabetes and longevity. A paper just published in the American Journal of Clinical Nutrition offers evidence that the valuable phenolic compound quercitin may be even more effective than resveratrol for reducing the inflammation associated with insulin resistance and diabetes. The authors state:

“Quercetin and trans-resveratrol (trans-RSV) are plant polyphenols reported to reduce inflammation or insulin resistance associated with obesity. Recently, we showed that grape powder extract, which contains quercetin and trans-RSV, attenuates markers of inflammation in human adipocytes and macrophages and insulin resistance in human adipocytes…The aim of this study was to examine the extent to which quercetin and trans-RSV prevented inflammation or insulin resistance in primary cultures of human adipocytes [fat cells] treated with tumor necrosis factor-{alpha} (TNF-{alpha})—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals.”

They stimulated fat cells with TNF-{alpha} to promote inflammation after pretreatment with quercetin and trans-RSV, then measured gene and protein markers of inflammation and insulin resistance. What did the data show?

Quercetin, and to a lesser extent trans-RSV, attenuated the TNF-{alpha}–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1… Quercetin, but not trans-RSV, decreased TNF-{alpha}–induced nuclear factor-{kappa}B transcriptional activity. Quercetin and trans-RSV attenuated the TNF-{alpha}–mediated suppression of peroxisome proliferator–activated receptor {gamma} (PPAR{gamma}) and PPAR{gamma} target genes and of PPAR{gamma} protein concentrations and transcriptional activity….”

Quercitin is known to be helpful for gut inflammation associated with food allergies, and I have found it to be a surprisingly helpful palliative for airborne allergies. In light of this the authors’ conclusion is not a surprise:

“These data suggest that quercetin is equally ormore effective than trans-RSV in attenuating TNF- ${alpha}$ –mediatedinflammation and insulin resistance in primary human adipocytes.”

Losing weight can release pollutants into the blood

Posted on September 10, 2010 by Dr. Jonathan

Adipose tissue (fat) is the body’s primary storage depot for environmental toxins. There they can be sequestered from the circulation and other tissues. A study just published in the International Journal of Obesity reveals that weight loss can release toxic pollutants into the circulation with potential adverse consequences for health. The authors state:

“There is emerging evidence that persistent organic pollutants (POPs) can increase the risk of various chronic diseases. As POPs mainly bioaccumulate in adipose tissue, weight change can affect serum concentrations of POPs.”

The authors set out to examine serum concentrations of seven POPs in association with weight change over 1 year and 10 year periods in 1,099 adults age 40 or older. What did their data show?

“Serum concentrations of most POPs were higher in those with long-term weight loss, whereas they were lower in those with long-term weight gain. Weight change for 1 year showed similar but weaker associations, compared with those of long-term weight changes.”

Their conclusion contains a note of irony:

“Although both beneficial health effects after weight loss and harmful health effects after weight gain are generally expected, changes in serum concentrations of POPs in relation to weight change may act on health in directions opposite to what we expect with weight change.“

There are ample resources in the functional medicine model to objectively investigate the release of toxins into circulation, the presence or absence of harm from them, and the capacity of the individual to metabolize and eliminate them efficiently. The complete picture is too extensive for this post, but the casual reader may be interested in simple tests for blood contamination by volatile solvents, polychlorinated biphenyls (PCBs), and chlorinated pesticides.

The tape measure: a powerful predictive ‘instrument’ for mortality

Posted on September 7, 2010 by Dr. Jonathan

More research recently published in the Archives of Internal Medicine further validates the power of waist circumference measurements to predict death from all causes. This study provides evidence that its accuracy is far superior to body mass index (BMI).

“Waist circumference (WC), a measure of abdominal obesity, is associated with higher mortality independent of body mass index (BMI). Less is known about the association between WC and mortality within categories of BMI or for the very high levels of WC that are now common.”

The authors examined the association between WC and mortality among 48 500 men and 56 343 women between 1997 and 2006, during which 9315 men and 5332 women died. Considering the adverse metabolic and hormonal activity of visceral (intra-abdominal versus subcutaneous) fat, their data is not surprising:

“After adjustment for BMI and other risk factors, very high levels of WC were associated with an approximately 2-fold higher risk of mortality in men and women…The WC was positively associated with mortality within all categories of BMI.”

Very high levels of WC means 47 inches for men and 43 inches for women. Waist circumference is a more reliable indicator than weight or BMI. If you’re losing weight without your WC getting smaller, you’re probably losing more muscle than fat. As the authors state in their conclusion:

“These results emphasize the importance of WC as a risk factor for mortality in older adults, regardless of BMI.”

Blood sugar and the brain in learning and behavioral disorders

Posted on September 5, 2010 by Dr. Jonathan

The brain needs a steady supply of glucose to work normally. Disorders of blood sugar regulation, whether hypoglycemia or insulin resistance (precursor to type 2 diabetes), deprives the brains cells of the fuel to produce the energy they need to function. Research just published in the journal Diabetologia examines the cognitive impairments present in adolescents when insulin resistance and overweight have progressed to type 2 diabetes.

“Central nervous system abnormalities, including cognitive and brain impairments, have been documented in adults with type 2 diabetes…Assessing adolescents with type 2 diabetes will allow the evaluation of whether diabetes per se may adversely affect brain function and structure years before clinically significant vascular disease develops.”

The authors compared two groups of overweight adolescents, one with and the other without type 2 diabetes. The depredations of insulin resistance on the brain were stunning:

“Adolescents with type 2 diabetes performed consistently worse in all cognitive domains assessed, with the difference reaching statistical significance for estimated intellectual functioning, verbal memory and psychomotor efficiency…[and] executive function, reading and spelling. MRI-based automated brain structural analyses revealed both reduced white matter volume and enlarged cerebrospinal fluid space in the whole brain and the frontal lobe in particular… In addition, assessments using diffusion tensor imaging revealed reduced white and grey matter microstructural integrity.”

The authors conclusion places both clinicians and parents on the alert:

“These abnormalities are not likely to result from education or socioeconomic bias and may result from a combination of subtle vascular changes, glucose and lipid metabolism abnormalities and subtle differences in adiposity in the absence of clinically significant vascular disease.”

On the hypoglycemic pole of glucose regulation we can appreciate earlier fascinating research published Pediatric Research documenting an impaired neurotransmitter response to falling blood sugar in children with ADD (the catecholamines epinephrine and norepinephrine attenuate the drop in blood sugar).

“Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children with attention deficit disorder (ADD)…metabolic, hormonal, and cognitive responses to a standard oral glucose load (1.75 g/kg) were compared in 17 children with ADD and 11 control children.”

Their data showed a significant difference between ADD and control children:

“The late glucose fall stimulated a rise in plasma epinephrine that was nearly 50% lower in ADD than in control children. Plasma norepinephrine levels were also lower in ADD than in control children…”

The authors’ conclusion indicates the need for conscientious blood sugar management through dietary and other measures:

“These data suggest that children with ADD have a general impairment of sympathetic activation involving adrenomedullary as well as well as central catecholamine regulation [of blood sugar].”

Similar phenomena are presented in a paper published in the Journal of the American Academy of Child & Adolescent Psychiatry describing abnormalities of brain metabolism in girls with ADHD:

“This study assesses the effect of attention-deficit hyperactivity disorder (ADHD) and gender on cerebral glucose metabolism (CMRglu), using positron emission tomography and 18F-fluorodeoxyglucose.”

An interesting gender difference emerged from the data:

“However, the global CMRglu in ADHD girls was 15.0% lower than in normal girls, while global CMRglu in ADHD boys was not different than in normal boys. Furthermore, global CMRglu in ADHD girls was 19.6% lower than in ADHD boys and was not different between normal girls and normal boys.”

Gender differences that must be respected are pronounced here and throughout medicine and biology:

“The greater brain metabolism abnormalities in females than males strongly stress that more attention be given to the study of girls with ADHD.”

Addressing the dysfunctions in blood sugar dysregulation associated with disorders of learning and behavior requires understanding that deleterious eating conducts can manifest as a form of self-medication. A paper recently published in Current Psychiatry Reports brings attention to this:

“In the past decade, we have become increasingly aware of strong associations between overweight/obesity and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults.”

The need to satisfy imperious physiological urges on a cellular level when an individuals genetic needs are not being met can overwhelm all advice and intention to acquire more wholesome and sustainable habits:

“It is also proposed—based on the compelling evidence that foods high in fat, sugar, and salt are as addictive as some drugs of abuse—that excessive food consumption could be a form of self-medication. This view conforms with the well-established evidence that drug use and abuse are substantially higher among those with ADHD than among the general population.”

True remediation demands a functional medicine approach to resolve the underlying cellular and metabolic needs that are not being met so they can be supported in a physiological and sustainable manner to restore normal function.

A paper published in the Journal of Nutrition, Health & Aging brings us back to the fundamental importance of glucose regulation for the brain.

“The regulation of glycaemia (thanks to the ingestion of food with a low glycaemic index ensuring a low insulin level) improves the quality and duration of intellectual performance, if only because at rest the brain consumes more than 50% of dietary carbohydrates, approximately 80% of which are used only for energy purpose. In infants, adults and aged, as well as in diabetes, poorer glycaemic control is associated with lower performances, for instance on tests of memory. At all ages, and more specifically in aged people, some cognitive functions appear sensitive to short term variations in glucose availability.“

Compulsive eating and dopamine receptor dysfunction

Posted on May 11, 2010 by Dr. Jonathan

As most of you well know, the neurotransmitter dopamine and its receptors are critical to the brain’s reward pathways, and dysfunction of these pathways is associated with addictive behaviors. This paper recently published in the journal Nature Neuroscience elucidates the role of dopamine receptors in compulsive eating with obesity. The authors first noticed that…

“…development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking.”

On investigating the underlying mechanism they found that compulsive feeding was present in obese but not lean rats because…

“Striatal (corpus striatum of the brain) dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs.”

What did they conclude from their data?

“These data demonstrate that overconsumption of palatable food [which produces insulin resistance] triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.”

Journal of Neuorendocrinology A paper published in the Journal of Neuroendocrinology adds further support to the importance of dopamine in appetite regulation. Ghrelin is a peptide produced in the stomach that increases appetite by stimulating a part of the brain (VTA = ventral tegmental area) that is rich in dopamine producing neurons:

“Interestingly, ghrelin infusions into the VTA increase food intake dramatically, and stimulate dopamine release from the VTA…ghrelin increases food intake by modulating the activity of dopaminergic neurones in the VTA.“

The author offers this conclusion:

“On the basis of these data as well as the fact that VTA dopamine cells respond to other metabolic hormones such as insulin and leptin, it is proposed that VTA dopamine cells…are first-order sensory neurones that regulate appetitive behaviour…”

Pharmacology Biochemistry Behavior Blood sugar and insulin have such a powerful effect on the brain and energy (nutrient) seeking behavior it’s no wonder there’s abundant evidence that they are associated with dopamine in the regulation of appetite. This paper published in Pharmacology Biochemistry and Behavior notes that:

“The hormones insulin, leptin, and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis…CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulators of energy homeostasis.”

Their research demonstrates that insulin and leptin can dampen reward satisfaction through an effect on dopamine signaling:

“Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, the midbrain dopamine (DA) and opioidergic pathways.”

Another study published in Acta Diabetologica also confirms the profound effect of insulin on dopamine signaling:

“Administration of various doses of glucose to rats produced a significant decrease of dopamine turnover…a close connection between 3,4-dihydroxyphenylacetic acid (DOPAC) (metabolite of dopamine) variation and insulin plasma level was demonstrated. However, glucose did not affect dopamine metabolism in starved or streptozotocin-treated rats (rats made to be diabetic). This indicates that the effect of glucose on the central dopaminergic system is mediated by pancreatic insulin, even in the presence of endogenous brain insulin.”

Moreover, dopamine gives the message that the cells are satisfied and shuts down pancreatic production of insulin as described in this paper published in The Journal of Biological Chemistry:

“Both dopamine and insulin actions in the brain modulate appetite and feeding behaviors. In this work we show for the first time that pancreatic beta cells express dopamine receptors mediating inhibition of glucose-stimulated insulin secretion.”

They go on to further describe the close association of dopamine with insulin and problems related to blood sugar regulation and obesity:

“Moreover, antipsychotic (neuroleptic) drugs blocking dopamine receptors may cause hyperinsulinemia, hypoglycemia, increase appetite, and obesity and are associated with diabetes. Therefore, dopamine action on beta cells (of the pancreas that secrete insulin)might have relevant implications for the study of obesity and diabetes, in particular in situations where dopamine transmission is altered.”

As if that wasn’t enough, the effect of insulin on dopamine signaling is so strong that it can even block the effects of amphetamine as described in this study published in PLoS Biology:

“Amphetamines mediate their behavioral effects by stimulating dopaminergic signaling throughout reward circuits of the brain. This property of amphetamine relies on its actions at the dopamine transporter (DAT)…we and others have revealed the novel ability of insulin signaling pathways in the brain to regulate DAT function as well as the…actions of amphetamine…by depleting insulin, or…insulin signaling, we can severely attenuate amphetamine-induced dopamine release and impair DAT function. Our findings demonstrate in vivo the novel ability of insulin signaling to dynamically influence the neuronal effects of amphetamine-like psychostimulants.”

The bottom line: compulsive eating (and other addictive behaviors) occurs when the reward (satisfaction) circuits are not functioning. To feel satisfied, we need adequate dopamine production and healthy insulin regulation. For the former we have natural precursor therapy to replenish exhausted dopamine resources. Healthy insulin and blood sugar regulation is, of course, a fundamental to any health strategy.

Mechanisms that link inflammation, obesity and cancer

Posted on May 5, 2010 by Dr. Jonathan

The latest issue of the Journal of the National Cancer Institute comments on recent research investigating how the inflammatory cytokines (cell signaling molecules), which are increased under various conditions that include obesity, can turn healthy liver cells into malignant ones:

“As obesity’s ties to multiple cancers strengthen, a new study suggests that inflammation may be the primary culprit in at least one malignancy: liver cancer.”

Cell The study itself was recently published in the journal Cell. The report that…

“We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice…Obesity-promoted HCC (hepatocellular carcinoma = liver cancer) development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3.”

Readers here will not be surprised that they also assert…

“The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.”

Three important points: (1) nothing increases the storage of fat in the liver like the high levels of insulin associated with insulin resistance (remember the link between insulin and fatty liver disease). (2) Chronic inflammation, whatever the cause, is a component of most chronic degenerative diseases. (3) Those of us who are health care professionals should be using the available laboratory tests for inflammatory cytokines in the care of our patients when appropriate; readers who are patients should be asking about them.

Normal weight obesity: heart disease from being fat without looking fat

Posted on May 1, 2010 by Dr. Jonathan

This study published not long ago in the European Heart Journal is consonant with my findings for certain patients (using bioelectric impedance analysis for body composition determination) who were slim in appearance but turned out to be metabolically obese. They had a proportionately large amount of fat packed around the internal organs that wasn’t apparent externally. High levels of visceral fat are associated with the chronic inflammation that is a fundamental cause of cardiovascular and other diseases. The authors of this paper suspected this phenomenon:

“We hypothesized that subjects with a normal body mass index (BMI), but high body fat (BF) content [normal weight obesity (NWO)], have a higher prevalence of cardiometabolic dysregulation and are at higher risk for cardiovascular (CV) mortality.”

They thoroughly evaluated 6171 subjects with body composition measurement, blood tests and cardiovascular risk factors. Their data showed that…

“The highest tertile of BF (>23.1% in men and >33.3% in women) was labeled as NWO. When compared with the low BF group, the prevalence of metabolic syndrome in subjects with NWO was four-fold higher. Subjects with NWO also had higher prevalence of dyslipidaemia, hypertension (men), and CV disease (women). After adjustment, women with NWO showed a significant 2.2-fold increased risk for CV mortality in comparison to the low BF group.”

This means that excessive levels of body fat can be present in someone of normal weight and appearance (“metabolic obesity”), contributing to cardiovascular damage in both men and women. In women there is a stronger association with death from cardiovascular disease.

The author’s conclusion:

“Normal weight obesity, defined as the combination of normal BMI and high BF content, is associated with a high prevalence of cardiometabolic dysregulation, metabolic syndrome, and CV risk factors. In women, NWO is independently associated with increased risk for CV mortality.”

Important: There are consumer devices such as scales marketed as bioelectric body composition instruments but these do not give accurate or reliable results. Dependability requires a medical-grade device that utilizes electrodes on both the lower and upper extremities along with validated algorithms.