Interactions between diet, physical activity and genetic predisposition contribute to variable body mass changes observed in response to weight loss interventions. Circulating microRNAs (c-miRNAs) may act as 'biomarkers' that are associated with the rate of change in weight loss, and/or play a role in regulating the biological variation, in response to energy restriction.
The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1beta and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and dopamine (DA) and an increase in serotonin concentration in tumor-bearing rats, in first- and second-order hypothalamic nuclei, while tumor resection reverted these changes and normalized food intake, suggesting negative regulation of NPY and DA systems by cytokines during anorexia, probably mediated by serotonin that appears to play a pivotal role in the regulation of food intake in cancer. Among the different forms of therapy, nutritional manipulation of diet in tumor-bearing state has been investigated. Supplementation of tumor bearing rats with omega-3 fatty acid vs. control diet delayed the appearance of tumor, reduced tumor-growth rate and volume, negated onset of anorexia, increased body weight, decreased cytokines production and increased expression of NPY and decreased alpha-melanocyte-stimulating hormone (alpha-MSH) in hypothalamic nuclei. These data suggest that omega-3 fatty acid suppressed pro-inflammatory cytokines production and improved food intake by normalizing hypothalamic food intake-related peptides and point to the possibility of a therapeutic use of these fatty acids. The sum of these data support the concept that immune cell-derived cytokines are closely related with the regulation of metabolism and have both central and peripheral actions, inducing anorexia via hypothalamic anorectic factors, including serotonin and dopamine, and inhibiting NPY leading to a reduction in food intake and body weight, emphasizing the interconnection of the immune and neuroendocrine systems in regulating metabolism during infectious process, cachexia and obesity.
Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30-70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state.
Vitamin D deficiency is a global health problem, its role as an immune modulator has been recently emphasized. The evidence is increasingly pointing towards vitamin D significant role in reducing the incidence of autoimmune diseases. However, at this time the research on its role in autoimmune and thyroid disease is not conclusive.
We aimed to examine the relationship between hypothyroidism and vitamin D deficiency and to clarify the relation between serum calcium levels with hypothyroid disease.
Both supplements of L-tryptophan and 5-HTP have been used in the treatment of depression, but the use of 5-HTP may offer the advantage of bypassing the conversion of L-tryptophan into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. Tryptophan hydroxylase can be inhibited by numerous factors, including stress, insulin resistance, vitamin B6 deficiency, and insufficient magnesium... Moreover, 5-HTP easily crosses the blood–brain barrier, and unlike L-tryptophan, does not require a transport molecule to enter the central nervous system (Green et al., 1980; Maes et al., 1990). Besides serotonin, other neurotransmitters and hormones, such as melatonin, dopamine, norepinephrine, and beta-endorphin have also been shown to increase following oral administration of 5-HTP. All of these compounds are thought to be involved in the regulation of mood as well as sleep and may represent mechanistic pathways stimulated by 5-HTP administration.
Folic acid deficiency has been found in people with depression and has been linked to poor response to antidepressant treatment. Homocysteine is considered a significant risk factor for cardiovascular disease and may be modified by B vitamins, including folate or derivatives. Daily doses of > or =0.8 mg folic acid are typically required to achieve the maximal reduction in plasma homocysteine concentrations produced by folic acid supplementation. Doses of 0.2 and 0.4 mg are associated with 60% and 90%, respectively, of this maximal effect. Homocysteine Lowering Trialists’ Collaboration.
Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.
Methylenetetrahydrofolate reductase (MTFHR) is an enzyme involved in the processing of amino acids using folic acid, specifically the conversion of homocysteine to methionine. Patients with C677T polymorphism may see increased levels of blood homocysteine when folate levels are low, which may lead to a need for folate supplementation. Various mutations to the MTFHR enzyme may result in altered need and response to folate supplementation.
L-Methylfolate is the centrally active derivative of the vitamin folate and is used for both neurotransmitter synthesis, and vital methylation reactions in all cells. It regulates BH4 (or tetrahydrobiopterin) a critical enzyme cofactor required for serotonin, dopamine and norepinephrine synthesis. Some forms of depression resistant to antidepressant treatment may respond to folate or l-methylfolate. Synthesis of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine is regulated by L-methylfolate, a derivate of the vitamin folate. Copyright 2008 Physicians Postgraduate Press, Inc.
Some research suggests that vitamin C may reduce cartilage loss and osteoarthritis progression. One randomized, placebo controlled crossover trial and showed that osteoarthritis pain significantly decreased in the vitamin C group in comparison to the placebo.
The objective of this article is to provide a review of the fundamental aspects of body fluid balance and the physiological consequences of water imbalances, as well as discuss considerations for the optimal composition of a fluid replacement beverage across a broad range of applications. Early pioneering research involving fluid replacement in persons suffering from diarrheal disease and in military, occupational, and athlete populations incurring exercise- and/or heat-induced sweat losses has provided much of the insight regarding basic principles on beverage palatability, voluntary fluid intake, fluid absorption, and fluid retention. We review this work and also discuss more recent advances in the understanding of fluid replacement as it applies to various populations (military, athletes, occupational, men, women, children, and older adults) and situations (pathophysiological factors, spaceflight, bed rest, long plane flights, heat stress, altitude/cold exposure, and recreational exercise). We discuss how beverage carbohydrate and electrolytes impact fluid replacement. We also discuss nutrients and compounds that are often included in fluid-replacement beverages to augment physiological functions unrelated to hydration, such as the provision of energy. The optimal composition of a fluid-replacement beverage depends upon the source of the fluid loss, whether from sweat, urine, respiration, or diarrhea/vomiting. It is also apparent that the optimal fluid-replacement beverage is one that is customized according to specific physiological needs, environmental conditions, desired benefits, and individual characteristics and taste preferences.
Magnesium is especially important in athletes because it is crucial for production of energy and the mineral is lost through sweating (~0.1 mmol/L). Several other electrolytes are lost in sweat including chloride (~30mmol/L), potassium (~5mmol/L), calcium (~0.5 mmol/L).
Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men.
Vitamin K is often supplemented alongside Vitamin D, since they both support bone health. In fact, taking both together will improve the effects of each, since they are known to work synergistically. Vitamin K may attenuate the risk for vitamin D overdosing.
It has long been known that insulin-like growth factor 1 (IGF1) causes an increase in the circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), the hormonally active vitamin D metabolite, by stimulating the expression and activity of the 1α-hydoxylase that produces 1,25(OH)2D in the kidney. Indeed, plasma 1,25(OH)2D is significantly higher in active than controlled acromegaly, with a tendency to hypercalcemia, hyperphosphatemia, and hypercalciuria. On the other hand, more recent data has suggested that vitamin D may contribute to determining IGF1 concentrations. Mice knockout for the vitamin D receptor (VDR) exhibit 30% lower IGF1 levels compared with WT animals and a significant increase in serum IGF1 was noted in response to vitamin D in two small cohorts of children. Furthermore, cross-sectional analyses of community-based cohorts disclosed a positive correlation between the concentrations of 25-hydroxyvitamin D (25(OH)D), the marker of vitamin D status, and IGF1. Here we first conducted an open-label, controlled study of the changes in circulating IGF1 following vitamin D supplementation in adults. Then, we asked whether the influence of vitamin D on IGF1 might be clinically relevant for the management of growth hormone deficiency (GHD), which relies on measurement of IGF1 levels.
In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor α and β were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.
Allostasis differs from homeostasis Vis-a` -Vis its emphasis on dynamic rather than static biological set-points, considerations of the brain’s role in feedback regulation, and view of health as a whole-body adaptation to contexts (Schulkin, 2003b). These insights have encouraged new ways of conceptualizing complex, multi-systemic biological activities where, as Heraclitus wrote, ‘‘the only constant is change’’. The allostatic load model expands the theory of allostasis by applying it to the cause and effects of chronic stress… Allostatic load (AL) represents the ‘wear and tear’ the body experiences when repeated allostatic responses are activated during stressful situations (McEwen and Stellar, 1993). Real or interpreted threats to homeostasis initiate the sympathetic– adrenal–medullary (SAM) axis release of catecholamines and the hypothalamic–pituitary–adrenal (HPA) axis secretion of glucocorti- coids that mobilize energy necessary for fight-or-flight responses (Sapolsky et al., 2000)… While adaptive acutely, chronic over-activation of SAM- and HPA-axis products induce a ‘domino effect’ on interconnected biological systems that overcompensate and eventually collapse themselves, leaving the organism susceptible to stress-related diseases (Korte et al., 2005; Lupien et al., 2006; McEwen, 1998b)… A key feature of allostasis, AL, and ultimately allostatic overload is that multiple mediators of adaptation are involved and interconnected in a non-linear network… At first, prolonged secretion of the stress hormones epinephrine, norepinephrine, and cortisol (antagonized by dehydroepiandosterone) can falter in their ability to protect the distressed individual and instead begin to damage the brain and body (McEwen, 2006a)… Over time, subsidiary biological systems compensate for the over and/or under production of primary mediators and in turn shift their own operating ranges to maintain abated chemical, tissue, and organ functions. This prodromal stage is referred to as the secondary outcomes, whereby metabolic (e.g., insulin, glucose, total cholesterol, high density lipoprotein cholesterol, triglycerides, visceral fat depositing), cardiovascular (e.g., systolic and diastolic blood pressure), and immune (e.g., fibrinogen, c-reactive protein (CRP)) parameters reach sub-clinical levels. The final stage of AL progression is allostatic overload, whereby the culmination of physiological dysregulations leads to disordered, diseased, and deceased endpoints referred to as tertiary outcomes.
Restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects
Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) decrease with aging and are important androgen and estrogen precursors in older adults. Declines in DHEAS with aging may contribute to physiological changes that are sex hormone dependent… DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women.
Hormone Precursor - DHEA decreases with age and replacement may help mitigate the effects of age-related physical decline through its role as a precursor to androgens and estrogens. “[T]he present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.”
DHEA has been studied for its affects on stress adaptation. “Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously.”
Low-dose GHR [growth hormone replacement] improves body composition and QoL [quality of life] as early as 1 month after commencement and the beneficial effects continue at 3 months. Most importantly, these changes occur in the absence of side-effects. We therefore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of AGHD [Adult Growth Hormone Deficiency].
Growth Hormone Deficiency - Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.
Inducing Endogenous Testosterone & Preserving Spermatogenesis - Low-dose hCG when given with exogenous testosterone for hypogonadotropic hypogonadism, maintains production of intratesticular testosterone (ITT) and sperm production
It is important to understand the inter-relationship between thyroid hormones and corticosteroids. If you address hypothyroidism it may push the cortisol more towards cortisone and increase cortisol clearance even more. Furthermore, thyroid hormone suppresses corticosteroid binding globulin, which may free up more cortisol and this could lead to negative feedback on endogenous production. Both situations could induce low cortisol, so as you address the thyroid you may have to be supporting adrenals too. [T]hyroid hormones exert different effects on the production of various carrier proteins in vivo. Whereas they stimulate the production of SHBG, they suppress the level of CBG and of their own carrier protein, TBG
In the study reported here we show that treatment of hypothyroid subjects with a combination of T4 plus slow-release T3 leads to a considerable improvement of serum T4 and T3 values, the T4/T3 ratio and serum TSH as compared to treatment with T4- only. Serum T3 administration with slow-release T3 did not show serum peaks, in contrast to plain T3.
Experimental and clinical evidence suggests that a TSH level within the reference range is not a sufficiently optimal marker of adequate thyroid hormone replacement therapy in hypothyroid patients… Conceivably, four different groups of hypothyroid patients could benefit from combination treatment with T4 and T3: 1) patients with hypothyroidism due to an under- lying autoimmune condition (38, 64, 65); 2) thyroidectomized patients or patients submitted to radioiodine activities resulting in a lack of sufficient endogenous thyroid function and absence of residual thyroidal T3 production (36); 3) patients with certain D2 polymorphisms (the enzyme responsible for T3 tissue availability) who tend to have a preference for combination T4/T3 replacement therapy (66, 67); and 4) depressed hypothyroid patients who might benefit from the antidepressant effect of lio-thyronine (68)…