My scientist friend asked how to detox or clean his body from toxins

Over the years, I have experienced family and friends dying of cancer. I observed their lifestyle and toxins they are exposed to. So to answer my friend’s question on how to detox and the mechanism of cleaning our body or getting rid of toxins, I listed some items for Dos and Donts.

Our lymphatic system which travels opposite our blood is responsible for cleaning our blood.  Search for lymphatic, massage and detox in this site

When we clean the many bad foods or toxins that entered our body, we must clean our liver first, our laboratory.  It is closely linked to our heart that during our last breath, our liver is the first and last signal that our heart gets to shut down.

Detox or cleaning our cells from toxins is the key to living longer, the anti-aging process we all are seeking for. In my 50s, I could have died long time ago if I was born centuries ago with no clean water, fresh produce and raising a dozen children. Each child is minus 5 years of a woman’s age.

Detox is like cleaning the toilet. The following are detox tips and anti-aging tips to clean your cells:

Dos in cleansing your body from toxin, also detoxes your liver

  • Massage
  • Adequate sleep
  • Filtered water
  • Lemon
  • Baking soda (pinch in your drinking water)
  • Activated charcoal
  • Digestive enzymes from pineapple and papaya
  • Apple cider vinegar
  • Wash produce with salt or diluted vinegar
  • No over ripe fruits and left over foods or 3-day old rice ( aflatoxin , mycotoxin )
  • No charred BBQ
  • Whole foods ; sulfur rich as they are anti-inflammatory (ginger, garlic, turmeric, coconut, walnuts)
  • Deep breathing thru nose and blow out thru mouth
  • Prayer: May God’s light energy be with you and say Amen to accept it.
  • Resveratrol from Berries, kiwi, citrus fruit
  • Fasting
  • Activated charcoal
  • Clean air

Donts are ways that when practiced or consumed can kills our nerve cells and produce toxins in our cells.

  • Avoidance of too much caffeine, iron and sugar, these are food for cancer
  • Other metal toxins
  • TRANS fat
  • Processed
  • Plastics in food
  • Stress
  • Shift work: not sleeping from 10pm to 4 am
  • Radiation
  • Over medications, chemo, other carcinogens
  • Avoid exposure to fumes, chemicals (formaldehydes,carcinogens,toxins)



Hi Connnie,

And what is your recipe for liver detox and the mechanism by which it works to accomplish that?

From: Male friend in his late 50s whose brother died of pancreatic cancer

Oxidative Stress, Inflammation, Thyroid and Anti-oxidant

Why is it harder for older people to lose weight? Is inflammed thyroid the culprit?

It can be anything from stress and hormones to poor nutrition, food sensitivities, bacteria in your gut, or toxins in your liver. It could even be the result of an event that happened decades ago that’s causing unhealthy coping patterns or emotional stress.

Although you may think you are past those things, they could still be triggering a reaction in your body and making you sick. In fact, they could be disrupting the thyroid hormones that virtually every cell in the body needs to work properly!

When something triggers a disruption in your thyroid hormone, everything can go awry, from your GI tract to your liver and kidney function. You may experience all kinds of symptoms: gas and bloating, unexplained weight gain, mood swings, rashes, fatigue, aches and pains, and so many others.

How do you balance reactive oxygen species and anti-oxidant species? Whole foods, less inflammed body, rest and sleep, exercise, sunshine and anti-oxidants. AgeLOC is one of its class in my opinion in helping our aging mechanism from oxidation, inflammation and aging.


Email or order AgeLOC to help your aging mechanisms at:

sponsor connie USW9578356

agelok youth 2agelok youth

Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

Balance of Reactive oxygen species and Anti-oxidant defenses

Oxidative stress (OS) is defined as an unbalance between the production of prooxidant substances and antioxidant defenses.

The most important prooxidants are the reactive oxygen species (ROS) and reactive nitrogen species (RNS) [1]. The ROS family includes superoxide anion, hydroxyl radical, hydrogen peroxide, and hypochlorous acid. The first three substances are produced in vivo mainly by the mitochondrial respiratory chain during the oxidative metabolism of energetic substrates [2, 3]. They are regulators of redox-sensitive pathways involved in cellular homeostasis [4] and influence some transcription factors, in addition to the endogenous antioxidant pool [4–7].

RNS are peroxynitrite, produced by the reaction of nitric oxide (NO) with superoxide, and nitrosoperoxycarbonate, formed by the reaction of peroxynitrite with carbon dioxide. ROS and RNS are considered important pathogenetic factors in different diseases [8]. Among them, a particular pathogenetic role is played by the free radicals, that is, superoxide anion and hydroxyl radical, that are molecules characterized by high chemical reactivity due to a single unpaired electron in the external orbital.

In some cell types, such as leukocytes, endothelial and mesangial cells, fibroblasts, thyrocytes, oocytes, Leydig cells, and adipocytes, ROS generation could play functional roles [9]. Dual oxidases (DUOX), enzymes crucial for hydrogen peroxide generation, are essential for thyroid peroxidase- (TPO-) catalyzed hormone synthesis [10]. Two oxidases of such family are present in thyroid (DUOX1 and DUOX2). They work in conjunction with DUOXA1 and DUOXA2, which are maturation factors that allow DUOX enzymes to translocate to the follicular cell membrane and exert their enzymatic activity [10]. In addition, NADPH oxidase 4 (NOX4) [11] is a new intracellular ROS generating system recently described in the human thyroid gland.

An increased ROS production by the respiratory chain resulting from the rise of the energetic demand or substrate availability [12], as occurs in obesity, or mitochondrial dysfunction or impairment, can produce cell damage and contribute to the pathophysiology of different diseases, such as inflammatory (e.g., rheumatoid arthritis) and cardiovascular (e.g., myocardial infarction) diseases [2].

A pathophysiological role of ROS has been also suggested in diabetes mellitus, in which oxidation accompanies glycation in vivoand the antioxidant capacity is decreased, resulting in increased susceptibility to oxidative stress [13].

Different defensive mechanisms that protect against the free radical damage have been characterized in various cellular localizations, including the endoplasmic reticulum, mitochondria, plasma membrane, peroxisomes, and cytosol [2]. Enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and transition-metal binding proteins, such as transferrin, ferritin, and ceruloplasmin, prevent the production of or rapidly inactivate free radicals. SOD accelerates the dismutation process of superoxide anion in hydrogen peroxide and molecular oxygen that normally occurs with a rate constant 104-fold lower. CAT detoxifies hydrogen peroxide by transforming it in water and molecular oxygen.

GPx also participates in hydrogen peroxide detoxification when hydrogen peroxide levels are high. In addition, GPx detoxifies lipid peroxides by transforming them in the corresponding alcohols. “Scavengers” molecules, including both water-soluble, such as albumin, bilirubin, ascorbic acid, urates and thiols, and liposoluble, such as Vitamin E and coenzyme Q10 (CoQ10), substances interrupt the lipid-peroxidation chain by reacting with and neutralizing the intermediate radicals.

The high diffusion rate of scavengers, particularly the liposoluble ones in biological membranes, allows them to intercept radicals and transform them into more stable molecules, thus stopping the radical chain. Sometimes scavengers can be regenerated.

A third defensive mechanism uses processes which remove the molecules damaged by the oxidative attack, allowing the reconstitution of normal structures (e.g., specific phospholipases remove the peroxidized fatty acids, making the enzymatic reacylation of damaged molecules possible) [2].

The production of ROS and RNS can occur at the cellular level in response to metabolic overload caused by the overabundance of macronutrients. In addition, mitochondrial dysfunction and endothelial reticulum stress contribute to adipose tissue metabolic derangement in obese patients [14, 15]. ROS generation is further maintained by an inflammatory response, feeding a vicious circle. This picture is worse in pre- and postpubertal children, because puberty alters some inflammatory markers associated with endothelial dysfunction (adipocytokine levels, OS, and insulin sensitivity).

Recent findings suggest that mitochondrial reactive species are signalling molecules that mediate the production of proinflammatory cytokines, thus connecting OS and inflammation. This topic has been extensively studied in cardiovascular diseases [16].

However, besides inflammation, OS can be related to hormonal derangement in a reciprocal way. Some hormones influence antioxidant levels; on the other hand, OS can modify synthesis, activity, and metabolism of hormones. Therefore, OS is related to both systemic inflammation and hormonal derangement. In particular, thyroid hormones play important roles in antioxidant modulation, as demonstrated in different in vitro and in vivo studies. Reduced glutathione (GSH) is an important cofactor of both antioxidant enzymes and deiodinases, the enzymes responsible for the conversion of thyroxine (T4) to triiodothyronine (T3).

Moreover, plasma levels of small antioxidant molecules, such as Vitamin E and CoQ10, and thyroid hormones are closely related to each other [2, 17]. Both hyperthyroidism and hypothyroidism have been shown to be associated with OS and special cases are the autoimmune thyroiditis or the functional picture of low-T3 syndrome, observed in acute and chronic nonthyroidal illness syndrome (NTIS) [17–19]. It is still debated whether NTIS represents an adaptive response or a real hypothyroidism at the tissue level. Therefore, studies on OS in NTIS are important to gain knowledge about the pathophysiology of the syndrome itself.

In this review, we firstly examine the relationships between OS and inflammation. Then, we present available data on thyroid hormones and antioxidant regulation. Finally, we report the results of investigations on the relationships between inflammatory mediators and OS in NTIS, in the attempt of hypothesizing a reciprocal influence between tissue hypothyroidism (as primary cause or secondary to inflammation) and OS. Thus, the aim of our review is to discuss and clarify the relationships between thyroid hormones and parameters of OS in the context of the inflammatory diseases.

2. Oxidative Stress and Inflammation

Different mediators produced by the adipose tissue may potentially cause an increase of systemic and local ROS and RNS. Thus, the dysregulation of signalling pathway originating in adipocytes, as observed in obese patients, can induce and perpetuate inflammation and OS. Recent studies clearly indicate that the adipose tissue can be considered as an endocrine organ producing different proteins (adipokines) with wide biologic activities. In addition, after maturation from the stage of preadipocytes, the adipocytes gain functions similar to those of macrophages, including the ability to be activated by components of the bacterial wall and to synthesize and secrete cytokines [20]. Moreover, during the periods in which weight gain or loss occurs, the cellular composition of the adipose tissue dynamically changes, showing variations in the levels of various cell types represented in the tissue, in particular vascular and immune cells.

The levels of the latter, in particular the macrophages, importantly increase in obese patients.

The macrophages seem to play important roles in the pathogenesis of insulin resistance associated with obesity, through the production of Monocyte Chemoattractant Protein-1 (MCP-1) and the modulation of the spreading and the growth of the adipose tissue itself [21]. Monocytes mobilized and attracted by MCP-1, together with neutrophils and lymphocytes T present in the adipose tissue, originate an inflammatory response that is reinforced by the stimulation of the synthesis and secretion of tumor necrosis factor (TNF) by macrophages, in turn induced by the increased production of free fatty acids (FFAs) by adipocytes. In addition, a two-way interaction between adipocytes and macrophages seems to develop, by which the macrophages stimulate the expression and release of MCP-1 from the adipocytes through ROS production.

By this way a vicious circle is established, which may promote a chronic inflammatory status gradually more and more intense, typical of obesity and its complications. Finally, the macrophages regulate the remodelling of the adipose tissue when a chronic positive energetic balance ensues. Different pathways are activated in adipocytes depending on whether subtype M1 or M2 macrophages are stimulated, that regulate adipocyte proliferation, growth, and survival. The induced changes are responsible for the appearance of a hypertrophic or hyperplastic obesity. In case of the prevalence the M1 proinflammatory macrophagic subtype, the reduced survival and proliferation of the preadipocytes will cause an inadequate adipocyte reserve; consequently, the energetic backlog, through an excessive hypertrophy, will produce a dysfunctional adipose tissue, which will perpetuate the inflammatory process and, in the long term, produce insulin resistance. Conversely, if the M2 macrophagic subtype is prevalent, the functional pool of preadipocytes will be favoured. They will differentiate into adipocytes, contributing to the formation of an adequate hyperplastic adipose tissue with preserved cell functions and insulin sensitivity [22].

Therefore, obesity is associated with increased secretion of proinflammatory hormones and cytokines (leptin, resistin, TNF-α, and interleukin- (IL-) 6) and decreased release of adipokines that downregulate inflammation (adiponectin, IL-10). Recent studies [23] show that not only the amount but also the kind of adipose tissue, as well as the kinds of fats in the diet, influence in different ways this chronic inflammatory state.

Many other mechanisms reviewed by Siti et al. [16] reinforce the link between OS and inflammation. Among these, there is the overexpression of endothelin that induces ROS production in endothelial cells by increasing NADPH oxidase activity [24]; on the other hand, OS causes an increase in angiotensin converting enzyme [25], creating a loop with the previously cited mechanism. Another important mechanism is the OS-induced Ca2+ influx, responsible for inflammatory processes [26].

In diabetes, the chronic inflammation, the increase in FFA levels, and the overactivation of the renin-angiotensin system contribute to insulin resistance via OS [27]. TNF-α, an important mediator of inflammation, interferes with insulin signals through the activation of the PI3-kinase pathway in endothelial cells [28]. A systemic lipid infusion, that induces acute elevation of plasma FFA levels, causes the activation of the NF-kB pathway, OS, and impairment of endothelium-dependent vasodilatation. In addition, insulin effects on vasodilatation, NO production, and muscle capillary recruitment are blunted by the lipid infusion [29–32]. Regarding this subject, we have shown that a naturally enriched antioxidant diet is capable of improving insulin sensitivity and metformin effects in adult obese patients [33].

Other studies confirmed the link between OS, vascular inflammation, and hypertension-associated vascular changes [34]. Moreover, it is well known that oxidized LDL have a key role in the initiation and progression of the atheromatous plaque [16, 35]; a main role has been recently attributed to the lectin-like oxidized LDL receptor-1 (LOX-1), which is upregulated by the exposure to inflammatory stimuli [36]. The role of the renin-angiotensin system in OS-related injury of endothelial cells has been recently reviewed [37]. Elegant studies conducted in experimental animal models, such as the ApoE knock-out mouse, confirmed an oxidant/antioxidant unbalance in the atherosclerotic process [38–40]. A large number of studies have been published on this topic, which, however, is not among the subjects of the present review. Nevertheless, they overall confirm the association between inflammation and OS.

3. The Role of Thyroid Hormones in Antioxidant Regulation

The role of thyroid in the regulation of the antioxidant systems has been recently reviewed in the context of the reproductive endocrinology [41]. It is well known that thyroid function influences the ovarian activity. ROS play physiological roles in the ovary and hypothyroidism, or a low-T3 syndrome, can induce ovarian dysfunction by interfering with the antioxidant systems.

OS has been shown to be associated with both hyperthyroidism and hypothyroidism [42]. However, the mechanisms by which OS is generated in these two clinical conditions are different: increased ROS production in hyperthyroidism and low availability of antioxidants in hypothyroidism.

Some complications of hyperthyroidism in target tissues are caused by OS [43]. Thyroid hormones per secan act as oxidants and produce DNA damage (contrasted by CAT), probably through the phenolic group, which is similar to that of steroidal estrogens [44]. Many other mechanisms, as previously reviewed [45], can be involved, in particular the enhanced Nitric Oxide Synthase (NOS) gene expression with NO overproduction and the activation of hepatic NF-kB with the consequent increase in cytokines levels which induces ROS production. On the other hand, other mechanisms regulated by thyroid hormones carry out a fine regulation of the oxidative status via autoloop feedback. Among them, we underline the role of Uncoupling Protein- (UCP-) 2 and Uncoupling Protein-3. Data obtained in plants and animals indicate that these molecules have antioxidant activity [46–48]. However, only T3 seems to regulate UCP, whereas no effect is exerted by T4 [49, 50]. An opposite effect is induced by estrogens, which increase ROS production by repressing UCP [51].

The increased turnover of mitochondrial proteins and mitoptosis also participate in the regulation of the oxidative status, by removing the mitochondria damaged by OS [52]. These processes are regulated by peroxisome proliferator-activated receptor gamma coactivator-1, which in turn is upregulated by T3administration [53].

Thyroid hormones influence lipid composition of rat tissues and consequently the susceptibility to OS.

However, the response is tissue-specific, and discrepant effects of T3 and T4 have been reported. In rat liver, T3-induced hyperthyroidism was found to be associated with altered lipid-peroxidation indexes, including elevated levels of thiobarbituric reactive substances (TBARS) and lipid hydroperoxides that are byproducts of lipid peroxidation [45, 53–55]. On the contrary, no changes in TBARS production were found in homogenized livers from rats made hyperthyroid by administration of T4 over a 4-week period [56]. No significant changes of TBARS or lipid hydroperoxides were observed in testes of hyperthyroid adult rats as well; however, hyperthyroidism promoted protein oxidation in testes, as indicated by the enhanced content of protein-bound carbonyls [57]. In addition, it should be emphasized that the effects of hyperthyroidism on the activity of antioxidant enzymes, including Mn- or Cu,Zn-SOD, CAT, and GPx, depend on the tissue investigated, with T3 and T4 having differentiated effects [58].

At the systemic level, hyperthyroidism has been associated with reduced circulating levels of alpha-tocopherol [59, 60] and CoQ10 [60, 61] in humans. CoQ10 showed a trend toward higher levels in hypothyroidism [61]. Thus, it seems to be a sensitive index of tissue effect induced by thyroid hormones in situations in which drug interference, such as treatment with amiodarone [62], or systemic illness inducing low-T3 conditions [63] complicate the interpretation of thyroid hormone levels.

On the other side, data on hypothyroidism and OS in humans are conflicting. In a group of patients with primary hypothyroidism, Baskol et al. [64] found high plasma levels of malondialdehyde (MDA), an OS marker that is formed by lipid peroxidation, and NO, low activity of paraoxonase- (PON-) 1, an enzyme synthetized in the liver with antioxidant properties, and SOD levels not significantly different from those of controls. Interestingly, the treatment with thyroid hormones decreased MDA levels and increased PON-1 activity, even though values similar to those observed in controls were not reached [64]. They hypothesized that in patients with hypothyroidism the prooxidant environment could play a role in the development of atherosclerosis. Elevated MDA levels were also shown in subclinical hypothyroidism [65]. In this setting, the increased OS was attributed primarily not only to the decrease in antioxidants levels, but also to altered lipid metabolism, since a significant correlation among MDA and LDL-cholesterol, total cholesterol, and triglyceride levels was found. Total antioxidant status (TAS) was similar in overt hypothyroidism, subclinical hypothyroidism, and controls.

Excess TSH is known to directly produce OS [66]. Other studies confirmed the lipid peroxidation both in overt hypothyroidism and in subclinical hypothyroidism [67] as indicated by MDA elevation; protein oxidation has been reported as well, with elevation of protein carbonyls [67]. In this study, the correlation analysis suggested that both the TSH increase and the MDA elevation contribute to protein damage. Finally, different studies reported NO elevation [68, 69].

Data on other parameters are more conflicting. As far as PON-1 is concerned, a decreased activity of this enzyme was observed both in hypothyroidism and in hyperthyroidism [70], whereas no significant differences with respect to controls were shown in other studies [68]. Increased levels of TBARS, but also antioxidants, such as SOD, CAT, and Vitamin E, have been also reported [71]. All these parameters correlated with T3 and the correlation between T3 and CAT remained significant also when corrected for total cholesterol. TBARS elevation was shown in both overt hypothyroidism and subclinical hypothyroidism [69, 72], but these findings were not confirmed in other studies [68, 73].

Another matter of discussion is whether OS is related to hypothyroidism per se or to lipid profile alterations caused by thyroid disfunction, as reported above. Indeed, Santi et al. [74] reported OS in subclinical hypothyroidism, as shown by reduced arylesterase and increased TBARS and CAT, but they attributed this pattern to hypercholesterolemia.

We showed low total antioxidant capacity (TAC) levels in hypothyroid patients [75] and increased CoQ10plasma levels in secondary hypothyroidism. This latter finding is mainly to be put in correlation with the metabolic role of CoQ10 in the mitochondrial respiratory chain and its consequent reduced cell use in hypothyroid patients. In secondary hypothyroidism, the picture is complicated by concomitant alterations of other pituitary-dependent axes, which can have opposite effect on CoQ10 plasma levels. Acromegaly and hypoadrenalism are characterized by low CoQ10 plasma concentrations; however, when they are associated with hypothyroidism, this latter has a predominant effect [75, 76].

New perspectives concern DUOX, DUOXA, and NOX4. Cases of hypothyroidism due to mutation of DUOX or DUOXA genes have been reported in the literature [10, 11]. In addition, alterations of NOX4 could be associated with thyroid cancer (via activation by H-Ras oncogene) and Hashimoto’s thyroiditis, in which the increased extracellular expression of this enzyme raises Intercellular Adhesion Molecule-1 (ICAM-1) expression and cytokine release [77, 78].

Finally, another study conducted on patients affected by subclinical hypothyroidism secondary to Hashimoto’s thyroiditis did not show any difference in endogenous MDA levels between hypothyroid patients and controls; however, MDA induction by the prooxidant 2,2′-azobis-(2-amidinopropane) hydrochloride was markedly augmented in hypothyroid patients. This response in serum was not accompanied by a similar pattern in the LDL fraction: in fact, copper-induced MDA production did not differ in patients affected by subclinical hypothyroidism with respect to controls, whereas it was significantly different from controls in patients with overt hypothyroidism [79]. Studies on patients with thyroiditis should be, however, interpreted with caution, in that both tissue inflammation and systemic inflammation are present in this autoimmune disorder.

The experimental procedures by which hypothyroidism is induced affect the OS findings. Hypothyroidism obtained by surgical thyroid resection in rats was associated with decreased OS in heart [80] and kidney [81]. On the contrary, drug-induced hypothyroidism was associated with increased lipid peroxidation in amygdala [82] and hippocampus in rats [82, 83]. Other cerebral areas, including the cerebellum, remained unaffected [84]. The latter findings, however, were not confirmed in other studies [82, 83]. Similarly, cell damage in various organs, including heart, spleen, liver, lung, and kidney, has been found in animals following methimazole treatment, but not after thyroidectomy [84]. Some studies, however, indicate that the organ damage is not consequent to the hypothyroidism per se, but to the drug itself [85, 86].

In the latest years, the attention has been concentrated on the damage induced by OS in certain organs, including liver, bone, skeletal muscle, and particularly the heart [53]. The metabolism of cardiomyocytes depends on serum T3, in that these cells lack a significant deiodinase activity [87]. Increased, decreased, or unmodified levels of total SOD, Mn-SOD, Cu,Zn-SOD, GPx, GSH, or Vitamin E have been reported in cardiomyocytes in response to hypothyroidism [88]. Unchanged or decreased levels of various other antioxidant molecules or parameters, such CoQ9, CoQ10, and TAC, have been also reported. These findings indicate that the evaluation of a single OS parameter is not a reliable index of the cellular oxidative status and the evaluation of TAC depends on the measurement method used.

OS has been also involved in the pathophysiology of schizophrenia. In fact, higher plasma levels of MDA and total plasma peroxides have been found in schizophrenic patients with respect to control subjects, which showed a significant correlation with T3 levels [89].

The thyroid itself can be damaged by OS, which occurs in case of iodine excess. This topic has been studied both in vitro and in animals fed with a diet rich in iodide [90, 91]. Iodide has a stimulatory action of on hydrogen peroxide generation in thyroid slices and induces thyroid cell apoptosis at high concentrations [92].

Vitamin E has been shown to be protective against the tissue damage induced by peroxyl radicals, mainly not only by preserving the polyunsaturated fatty acids in biological membranes, but also by reducing the activity of NADPH oxidase [53].

4. The Model of Low-T3 Syndrome

Low-T3 syndrome is a condition characterized by a reduced peripheral conversion of T4 to T3 in the presence of normal thyroid hormone secretion. It occurs in a variety of nonthyroidal illness (NTI) and is defined as nonthyroidal illness syndrome (NTIS). The most important acute conditions in which the low-T3syndrome occurs include starvation and eating disorders and critical illness. During starvation (especially carbohydrate deprivation) and nonthyroid illness, deiodination of T4 to T3 is rapidly inhibited, causing the low-T3 syndrome. As the illness progresses to more and more severe stages, a more complex syndrome with low-T3 and T4 ensues. In critical illness, many other changes of the pituitary-thyroid axis have been shown, including attenuated response to TRH, low tissue uptake of thyroid hormones, and altered thyroid hormone metabolism. A low-T3 syndrome caused by the reduced peripheral conversion from the prohormone T4 is also observed in different chronic diseases, including chronic kidney disease, liver failure, and chronic inflammatory diseases.

A component of NTIS can be related to cachexia, which is common in chronic systemic inflammation, renal failure, and heart failure. This field has been widely investigated in cancer patients. Cachexia represents a hypermetabolic wasting syndrome with progressive depletion of adipose tissue and skeletal muscle mass, often accompanied by anorexia [93]. Among the mediators of cachexia in cancer patients there are several cytokines and hormones also involved in the pathophysiology of NTIS. They are produced by tumour cells or macrophages surrounding them, as expression of the interaction between the neoplasia and the host environment. The most important are TNF-α, IL-1, IL-6, interferon- (IFN-) γ, proteolysis-inducing factor (PIF), angiotensin II, and myostatin, a member of the transforming growth factor-β superfamily. Interestingly, the signal transduction pathways of many of these substances involve NF-kB, the activity of which is in turn related to ROS levels. In fact, it has been shown that hydrogen peroxide, PIF, and angiotensin II activate NF-kB in myotubes [94] and the treatment of myotubes exposed to TNF-α, PIF, or angiotensin II with antioxidants reduces the NF-kB binding to DNA [94, 95]. In addition, it has been reported that the treatment of MAC16 colon-tumour bearing mice with Vitamin E reduces protein degradation in skeletal muscle [95]. Finally, some cytokines, including TNF-α, IL-1, IL-6, and IFN-γ, mimic leptin signalling, inducing central suppression of appetite [96].

The condition of NTIS is considered as an adaptive response rather than true hypothyroidism. Thyroid replacement therapy is not usually required, but this topic is still debated, since indirect signs of true hypothyroidism at tissue level have been shown. Some molecular mechanisms of NTIS are known, but more studies are necessary to further elucidate its pathogenesis. Indeed, it is probable that a full understanding of the pathophysiological mechanisms at the tissue level will allow the identification of patients who would benefit from replacement therapy. Our discussion will focus on the roles of cytokines and OS in the pathophysiology of NTIS.

The roles of cytokines as key molecules involved in coordinating the hormone, immune, and inflammatory responses to a variety of stressful stimuli are well known [18]. In a series of septic patients studied shortly after admission to the ICU, total T4 (tT4), free T4 (fT4), total T3 (tT3), and TSH plasma concentrations were depressed, and plasma levels of IL-1β, sIL-2 receptor, and TNF-α were elevated [97], indicating the establishment of central TSH suppression. The hypothalamic-pituitary-adrenal axis was activated as expected. Continuous infusion of IL-1 in rats causes reduction of TSH, free T3 (fT3), and fT4 plasma levels. Higher doses of IL-1 induced a febrile reaction and suppression of food intake, with a cascade of events altering thyroid hormone economy [98]. However, IL-1 did not decrease the hepatic 5′-deiodinase activity that, on the contrary, is typically reduced in NTIS.

TNF is another proinflammatory cytokine that is thought to be involved in many of the alterations associated with NTIS. Infusion of rTNF in man decreases serum T3 and TSH and increases reverse-T3(rT3) [99]. These findings suggest that TNF could be involved in the IL-6-mediated suppression of the hypothalamic-pituitary axis. However, the involvement of TNF in NTIS pathophysiology was not confirmed in other studies, in which the effects of endotoxin on thyroid hormones in humans were not counteracted by TNF-α blockade through specific IgG fusion proteins [100]. TNF-α was found in in vitrostudies to activate NF-kB [101], which in turn inhibits T3-induced expression of deiodinase 1 (D1).

An important pathophysiological role in NTIS has been attributed to IL-6, which is often elevated in serum of NTIS patients [102] in an inversely proportional manner with respect to T3 levels [103]. Short term infusion of rIL-6 to healthy volunteers [104] suppressed TSH secretion, whereas daily injections over a 6-week period only slightly decreased T3 levels and transiently increased rT3 and fT4 concentrations.

Deiodinases are dimeric selenoproteins that catalyze the stereospecific removal of iodine atoms from the prohormone T4, generating the active and inactive isomers of both T3 and diiodothyronine (T2). Different isoforms are expressed with tissue specificity: D1 and D2, via the deiodination of the outer ring, convert T4to active T3; D3, via the inner ring deiodination, converts T4 to inactive metabolites: rT3 and 3,3′-T2 [105, 106]. Phylogenetic analysis suggests that D1 is the oldest vertebrate deiodinase, while D2 is the most recent one; this is in agreement with the key role of D2 as the most specialized and finely regulated member of this enzyme family [106].

Deiodinases play pivotal roles in the regulation of the intracellular levels of active thyroid hormones [107]. D2 is located in the endoplasmic reticulum and plays the primary role in the conversion of T4 to T3. D1 has lower affinities for the substrates with respect to D2 and seems to be mainly a scavenger enzyme, involved in iodine recycling. Furthermore, the balance between D2 and D3 activities seems to be an important factor in determining the amount of T3 available to bind the nuclear receptors. Different mechanisms regulate the expression of deiodinase genes (DIO1, DIO2, and DIO3), first of all the levels of thyroid hormones: hyperthyroidism suppresses D2 activity and DIO2 expression, whereas hypothyroidism exerts the opposite effects [108]. The ubiquitination of the enzymes, which can be reversible to assure the appropriate protein homeostasis, is a mechanism of finer regulation of deiodinase activity [109].

D2 plays important roles in the regulation of the energetic balance as well. It has been shown that animal exposure to low temperatures activates D2 in brown adipose tissue through catecholamine-induced cAMP production. The resulting increase in T3 levels induces thermogenic genes, including UCP-1 [110]. In addition, DIO2 expression is upregulated by bile acids in the brown adipose tissue of mice through the increase in cAMP levels. When fed with a high fat diet supplemented with bile acids, the animals do not gain weight, showing a resistance to diet-induced obesity, and this effect is absent in D2 knock-out animals [111, 112].

Recent studies on the effects of IL-6 on both endogenous cofactor-mediated and dithiothreitol-stimulated deiodinase activity in human cell lines [112] have shown that T3 generation by D1 and D2 is suppressed by IL-6, despite an increase in expression of deiodinases. The inhibitory action of IL-6 is prevented by the addition of N-acetyl-cysteine (NAC), an antioxidant that restores intracellular GSH concentrations, suggesting the involvement of prooxidant substances in IL-6-induced effects.

Finally, the interaction between the complex network of cytokines and the hypothalamic-pituitary-thyroid axis probably plays pathogenetic roles in NTIS, even though it is not possible to build a simplistic model [18]. Also the role of cytokines in eating disorders and related thyroid hormone alterations has been recently reviewed [113].

Different conditions in which NTIS develops are associated with OS, due to augmented production ROS or RNS [114]. Since thyroid hormones, as above discussed, increase ROS generation, low-T3 could be viewed as a compensatory mechanism. In fact, low-T3 concentrations would be associated with decreased metabolic rate that would reduce further radical generation. Cytosolic thiols, particularly GSH, and Thioredoxin (Trx), which are also deiodinase cofactors, contribute to the maintaining of a reducing intracellular environment. Thus, their depletion, consequent to their buffering effect on radical propagation, could interfere with the conversion of T4 to T3 [115]. The nuclear sequestration of SECIS binding protein 2 (SBP2), which reduces the incorporation of selenocysteine residues in the selenoproteins [116], might be another mechanism. It is well known that IL-6 induces OS, so that a unifying mechanism might be that cytokine-induced OS alters secondarily the expression and activity of deiodinases [115]. The contribution of the reduction in the levels of thiol cofactor of deiodinases, consequent to the increase in intracellular ROS concentrations, has been suggested by other authors [117].

On the basis of the pathophysiological studies available in the literature, we can conclude that the alterations of the pituitary-thyroid axis depend not only on the severity of the disease, but also on the inflammatory response and the patients’ nutritional status. They also indicate that low-T3 is simply not an adaptive mechanism, but it is associated with tissue hypothyroidism and OS.

A special, reevaluated role could be played by selenium. This essential trace element exerts complex effects on the endocrine system, due to its antioxidant capacity; it is a cofactor of GPx and Trx reductase (TrxR), enzymes that protect the cells from the oxidative damage [118]. On the other hand, selenium is involved in the mechanisms of deiodination: a proposed model involves the formation of selenenyl iodide intermediate [119], even though the catalytic mechanisms and the regulation of deiodinases by selenium are not fully understood [120]. Thus, because of its double function, molecules that compete with this element could, in a reciprocal way, connect hypothyroidism due to low-T3 and OS. This hypothesis is supported by the evidence that NAC, an antioxidant that restores intracellular GSH levels, prevents the IL-6-induced effects on the intracellular redox state [121, 122]. In addition, the administration of sodium selenite in cells expressing deiodinases decreases the IL-6-induced ROS production and carbonyl protein content and enhances GPx and TrxR activities [123].

Also deiodinases may be involved in NTIS pathophysiology, with possible tissue specificity [124]. DIO1 is a T3-responsive gene; thus, D1 activity and intracellular T3 concentrations can affect each other in a reciprocal way. D1 activity has been shown to be suppressed in hepatocytes. The activity of D2 has been reported to be reduced [125], unchanged [126], or increased [127] in skeletal muscle. An increase in DIO2 expression in skeletal muscle has been reported in mice during chronic inflammation that has been linked to enhanced CREB signaling [128]. On the contrary, skeletal muscle DIO2 expression was found to be decreased in sepsis and this decrease was related to the reduction in food intake [129]. DIO2 expression increases in lung and in endothelial cells following LPS-induced injury [130] and in hepatic resident macrophages during acute and chronic inflammation [128]. As far as D3 is concerned, a decrease in DIO3 mRNA levels has been reported in liver during inflammation and sepsis [131, 132]. On the contrary, hepatic expression and activity of D3 were found to be increased in rabbits with prolonged critical illness [133]. Similarly, D3 activity was found to be increased in the skeletal muscle of critically ill patients [134] and in patients after myocardial infarction [135, 136].

In summary, even if the picture appears to be quite complex, some of these changes are mediated by inflammatory pathways, such as NF-kB and AP-1, whereas the CREB pathway seems to be predominant in skeletal muscle [124]. On the other hand, overexpression of D2 in tanycytes, that has been observed in rats after LPS infusion [117, 137, 138], could be responsible for central suppression of the hypothalamic-pituitary-thyroid axis, thereby contributing to the complex picture of the regulation of thyroid function in this clinical condition.


In conclusion, OS seems to be an important mechanism underlying the progress of inflammation. A vicious circle creates a link between these two conditions. Thyroid hormones can have a protective role, modulating antioxidant levels; on the other side, a tissue hypothyroidism can worsen OS (Figure 1). An interesting model is represented by NTIS, in which IL production due to inflammation can reduce the expression of deiodinases, inducing low-T3 levels and consequently a condition of tissue hypothyroidism. In turn, this latter could cause further OS (Figure 2).

These pathophysiological observations suggest the possible therapeutic efficacy of antioxidants in the NTIS.

Figure 1
Proposed model of the interrelationships between inflammation, oxidative stress, and thyroid derangement. Inflammation, via hormone and cytokine changes, leads to oxidative stress and also affects thyroid function, causing nonthyroidal illness syndrome …

Figure 2
Both hyperthyroidism and hypothyroidism can cause oxidative stress but with different mechanisms. We speculate that nonthyroidal illness syndrome (NTIS) may represent a tissue hypothyroidism condition linked to intracellular and systemic oxidative stress. …

Low glucose and low stress to go to sleep

There are many factors that will help you go to sleep. There are two most important factors.  One is that if you eat (few bites) sugary snacks (couple it with fish oil or omega 3), it should be 6 to 8 hrs before your sleep time. And the other one is that your stress level should be very low.

The pituitary gland is responsible for sleep, stress, sex hormones and food cravings.

Our gut microbiome (bacteria and microbes in our intestines) also communicates to our brain to tell us that they are busy or hungry.

When we have food cravings during the day, it is because we did not get quality sleep the night before.

When we are grumpy or stressed out that day, it also means that we did not get good sleep.

Our liver was not able to detox properly, so we have not so healthy skin as a result of poor quality sleep.

Our bedroom must be dimmed since lights tell our pituitary gland that it is not night time yet.

circ ry.JPG

So what did I do to go to sleep at 12 midnight after working making egg rolls until 9pm and eating chocolate desserts at that time? I have to wait till I calm my body and waited till 12midnight to go to sleep. I repeated some prayers to tell my brain to stop worrying or de-stress.  All these even after I took some important dietary supplements to go to sleep (melatonin, calcium and magnesium, Vit D3, zinc, Zyflamend night time caps).

Lesson: Our body needs low glucose and low stress to go to sleep.

Adrenal fatigue

Adrenal fatigue or hypoadrenia are terms used in alternative medicine to describe the unscientificbelief that the adrenal glands are exhausted and unable to produce adequate quantities of hormones, primarily the glucocorticoid cortisol, due to chronic stress or infections.[1] Adrenal fatigue should not be confused with recognized forms of adrenal dysfunction such as adrenal insufficiency or Addison’s Disease.[2]

The term “adrenal fatigue”, which was coined in 1998 by James Wilson, a chiropractor,[3] may be applied to a collection of mostly nonspecific symptoms.[1] There is no scientific evidence supporting the concept of adrenal fatigue and it is not recognized as a diagnosis by the medical community.[1][2]

Blood or salivary testing is sometimes offered but there is no evidence that adrenal fatigue exists or can be tested.

Pituitary gland

In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 grams (0.018 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypophysis rests upon the hypophysial fossa of the sphenoid bone in the center of the middle cranial fossa and is surrounded by a small bony cavity (sella turcica) covered by a dural fold (diaphragma sellae).[2] The anterior pituitary (or adenohypophysis) is a lobe of the gland that regulates several physiological processes (including stress, growth, reproduction, and lactation). The intermediate lobe synthesizes and secretes melanocyte-stimulating hormone. The posterior pituitary (or neurohypophysis) is a lobe of the gland that is functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk (also called the infundibular stalk or the infundibulum).

Hormones secreted from the pituitary gland help control: growth, blood pressure, certain functions of the sex organs, thyroid glands and metabolism as well as some aspects of pregnancy, childbirth, nursing, water/salt concentration at the kidneys, temperature regulation and pain relief.



park 3

park 2.jpeg

Parkinson’s disease and Mitochondria as the oxygen-consuming power plants of human cells

  • Mitochondrial maintenance is essential for cellular and organismal function.
  • Maintenance includes reactive oxygen species (ROS) regulation, DNA repair, fusion–fission, and mitophagy.
  • Loss of function of these pathways leads to disease.

Mitochondria are the oxygen-consuming power plants of cells. They provide a critical milieu for the synthesis of many essential molecules and allow for highly efficient energy production through oxidative phosphorylation. The use of oxygen is, however, a double-edged sword that on the one hand supplies ATP for cellular survival, and on the other leads to the formation of damaging reactive oxygen species (ROS). Different quality control pathways maintain mitochondria function including mitochondrial DNA (mtDNA) replication and repair, fusion–fission dynamics, free radical scavenging, and mitophagy. Further, failure of these pathways may lead to human disease. We review these pathways and propose a strategy towards a treatment for these often untreatable disorders.

Regarding mitophagy, two landmark papers showed that PINK1 and Parkin, two proteins mutated in familial Parkinson’s disease, are involved in the selective degradation of damaged mitochondria 16 and 100. Loss of these proteins may contribute to the accumulation of damaged mitochondria and death of dopaminergic neurons in the substantia nigra in the mesencephalon.

Further support of a mitochondrial etiology in Parkinson’s disease comes from the early observations that exposure to various mitochondrial toxins leads to Parkinson’s disease in humans and rodents [101]. Interestingly, Parkinsonism is relatively rare in primary mitochondrial diseases indicating that mitochondrial dysfunction does not automatically lead to dopaminergic neuronal death.

Conversely, Parkinson’s disease is not characterized by the severe neurodegeneration that commonly debuts in early adulthood in primary mitochondrial diseases. This may indicate that alternative mitophagy pathways may compensate for defects in PINK1 or Parkin [102] or that mitophagy plays a relatively minor role in overall mitochondrial maintenance. Recent findings of defective mitophagy in neurodegenerative accelerated aging disorders do, however, support a significant role of this pathway in overall mitochondrial maintenance [49].

Mitochondrial genetics

Mitochondria are a dynamic network of organelles constantly adapting their morphology and function to accommodate the needs of the cell. They are composed of an outer membrane, an intermembrane space, a highly folded inner membrane (the cristae), and a matrix space. Due to the prokaryotic origin of this organelle, the inner mitochondria membrane contains a specialized phospholipid, cardiolipin, that is also found in bacteria. More importantly, mitochondria contain their own DNA. The human mitochondrial genome, mtDNA, is a small circular ∼16.6 kilobase molecule that resides inside the matrix space associated with the inner membrane of the mitochondria [1]. mtDNA in humans encodes 13 polypeptides, 22 tRNAs, and two ribosomal genes that are essential for oxidative phosphorylation, the metabolic process by which cells convert energy stored in a range of different substrates to ATP, which is the energetic currency of the organism. All of the remaining mitochondrial proteins, including gene products necessary for mtDNA replication, transcription, and DNA repair, are derived from nuclear genes and are imported into the mitochondria, typically, but not exclusively, via a mitochondrial targeting sequence [2]. In addition to the role of mitochondria in ATP production, this organelle is also central in apoptosis, heme and steroid synthesis, Ca2+ regulation, adaptive thermogenesis, and other processes. Proper mitochondrial function is therefore critical for organismal health.

An understanding of mtDNA inheritance and maintenance patterns is essential for comprehending mitochondrial dysfunction in disease. mtDNA is packaged into protein–DNA structures called nucleoids containing one or more mtDNA genomes within a single nucleoid. Additionally, there are a few to several thousand copies of mtDNA per cell varying with cell type [3]. Cells can simultaneously carry a mixture of normal and mutated mitochondrial genomes, a condition known as heteroplasmy. Mutant mtDNA can be propagated along with normal mtDNA, when there is no selection pressure against the mutant genome, thereby contributing to the high sequence evolution of mtDNA [4]. When a cell divides and the nucleoids are segregated between the two daughter cells, the proportion of mutant to normal mtDNA can shift [5]. This has important ramifications for mitochondrial disease since the relative proportion of mutant mtDNA molecules must reach a certain threshold before a disease phenotype is observed.

Bona fide primary mitochondrial diseases represent a heterogeneous group of disorders most often involving multiple organ systems leading to progressive degeneration and in many cases early death. Since the combined prevalence is estimated to be around 1:5000, a mitochondrial etiology should be considered when encountering any patient, particularly children, with multisystem pathology in tissues such as the central nervous system, heart, skeletal muscles, liver, and in rarer cases kidney [6]. The pathogenic mutation can be located either within the mitochondrial or nuclear genome and, as in the case of mutations in Twinkle or DNA polymerase γ (POLG), can give rise to a great diversity of clinical syndromes (Figure 1).

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

Figure 1  Human mitochondrial DNA map showing representative pathogenic and adaptive base substitution mutations. D-loop = control region (CR). Letters around the outside perimeter indicate cognate amino acids of the tRNA genes. Other gene symbols are defined in the text. Arrows followed by continental names and associated letters on the inside of the circle indicate the position of defining polymorphisms of selected region-specific mtDNA lineages. Arrows associated with abbreviations followed by numbers around the outside of the circle indicate representative pathogenic mutations, the number being the nucleotide position of the mutation. Abbreviations: DEAF, deafness; MELAS, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes; LHON, Leber hereditary optic neuropathy; ADPD, Alzheimer and Parkinson disease; MERRF, myoclonic epilepsy and ragged red fiber disease; NARP, neurogenic muscle weakness, ataxia, retinitis pigmentosum; LDYS, LHON + dystonia; PC, prostate cancer.


As a toxic by-product of OXPHOS, the mitochondria generate most of the endogenous ROS. ROS production is increased when the electron carriers in the initial steps of the ETC harbor excess electrons, i.e., remain reduced, which can result from either inhibition of OXPHOS or from excessive calorie consumption. Electrons residing in the electron carriers; for example, the unpaired electron of ubisemiquinone bound to the CoQ binding sites of complexes I, II, and III; can be donated directly to O2 to generate superoxide anion (O•-2). Superoxide O•-2 is converted to H2O2 by mitochondrial matrix enzyme Mn superoxide dismutase (MnSOD, Sod2) or by the Cu/ZnSOD (Sod1), which is located in both the mitochondrial intermembrane space and the cytosol. Import of Cu/ZnSOD into the mitochondrial intermembrane space occurs via the apoprotein, which is metallated upon entrance into the intermembrane space by the CCS metallochaperone (166, 207). H2O2 is more stable than O•-2 and can diffuse out of the mitochondrion and into the cytosol and the nucleus. H2O2 can be converted to water by mitochondrial and cytosolic glutathione peroxidase (GPx1) or by peroxisomal catalase. However, H2O2, in the presence of reduced transition metals, can be converted to the highly reactive hydroxyl radical (•OH) (Figure 2). Iron-sulfur centers in mitochondrial enzymes are particularly sensitive to ROS inactivation. Hence, the mitochondria are the prime target for cellular oxidative damage (241, 242).

The mitochondria are also the major regulators of apoptosis, accomplished via the mitochondrial permeability transition pore (mtPTP). The mtPTP is thought to be composed of the inner membrane ANT, the outer membrane voltage-dependent anion channel (VDAC) or porin, Bax, Bcl2, and cyclophilin D. The outer membrane channel is thought to be VDAC, but the identity of the inner membrane channel is unclear since elimination of the ANTs does not block the channel (98). The ANT performs a key regulatory role for the mtPTP (98). When the mtPTP opens, ΔP collapses and ions equilibrate between the matrix and cytosol, causing the mitochondria to swell. Ultimately, this results in the release of the contents of the mitochondrial intermembrane space into the cytosol. The released proteins include a number of cell death-promoting factors including cytochrome c, AIF, latent forms of caspases (possibly procaspases-2, 3, and 9), SMAD/Diablo, endonuclease G, and the Omi/HtrA2 serine protease 24. On release, cytochrome c activates the cytosolic Apaf-1, which activates the procaspase-9. Caspase 9 then initiates a proteolytic cascade that destroys the proteins of the cytoplasm. Endonuclease G and AIF are transported to the nucleus, where they degrade the chromatin. The mtPTP can be stimulated to open by the mitochondrial uptake of excessive Ca2+, by increased oxidative stress, or by deceased mitochondrial ΔP, ADP, and ATP. Thus, disease states that inhibit OXPHOS and increase ROS production increase the propensity for mtPTP activation and cell death by apoptosis (Figure 2) (241, 242).

Clinical symptoms appear when the number of cells in a tissue declines below the minimum necessary to maintain function. The time when this clinical threshold is reached is related to the rate at which mitochondrial and mtDNA damage accumulates within the cells, leading to activation of the mtPTP and cell death, and to the number of cells present in the tissue at birth in excess of the minimum required for normal tissue function. Given that the primary factor determining cell metabolism and tissue structure is reproductive success, it follows that each tissue must have sufficient extra cells at birth to make it likely that that tissue will remain functional until the end of the human reproductive period, or about 50 years. If the mitochondrial ROS production rate increases, the rate of cell loss will also increase, resulting in early tissue failure and age-related disease. However, if mitochondrial ROS production is reduced, then the tissue cells will last longer and age-related symptoms will be deferred (236, 238, 241) (Figure 3).

Type II diabetes thus involves mutations in energy metabolism genes including the mtDNA and glucokinase; mutations in the transcriptional control elements PPARγ, PGC-1, HNF-1α, HNF-4α, and IPF-1; and alterations in insulin signaling. These seemingly disparate observations can be unified through the energetic interplay between the various organs of the body.

Notorious variability in the presentation of mitochondrial disease in the infant and young child complicates its clinical diagnosis. Mitochondrial disease is not a single entity but, rather, a heterogeneous group of disorders characterized by impaired energy production due to genetically based oxidative phosphorylation dysfunction. Together, these disorders constitute the most common neurometabolic disease of childhood with an estimated minimal risk of developing mitochondrial disease of 1 in 5000. Diagnostic difficulty results from not only the variable and often nonspecific presentation of these disorders but also from the absence of a reliable biomarker specific for the screening or diagnosis of mitochondrial disease. A simplified and standardized approach to facilitate the clinical recognition of mitochondrial disease by primary physicians is needed. With this article we aimed to improve the clinical recognition of mitochondrial disease by primary care providers and empower the generalist to initiate appropriate baseline diagnostic testing before determining the need for specialist referral. This is particularly important in light of the international shortage of metabolism specialists to comprehensively evaluate this large and complex disease population. It is hoped that greater familiarity among primary care physicians with the protean manifestations of mitochondrial disease will facilitate the proper diagnosis and management of this growing cohort of pediatric patients who present across all specialties.


Increased oxidative stress due to coenzyme Q10 (CoQ10) deficiency leads to an adaptive increase in autophagy [112]. Additionally, it has recently been shown that a defect in mitochondrial protein maintenance can augment autophagy [113]. It follows that a decrease in ROS production will lead to a decrease in the mitochondrial maintenance pathways. This tight regulation of mitochondrial maintenance through ROS is a possible explanation for the disappointing results antioxidants have shown in some human trials.

Food sources: COQ10

CoQ10 is naturally found in high levels in organ meats such as liver, kidney, and heart, as well as in beef, sardines, and mackerel. Vegetarians or vegans who are used to eating these foods should find a suitable alternative. Luckily, vegetable sources of CoQ10 include spinach, broccoli, and cauliflower.


Includes lean meats, poultry, seafood, beans and peas, eggs, and nuts and seeds. Pork, beef, turkey, chicken, fish, shellfish, mushrooms, whole grains and eggs contain high amounts of selenium. Some beans and nuts, especially Brazil nuts, contain selenium.

A link to your signup form:

Subscribe to our mailing list

Powered by Robly

Date/Argentine Tango partner needed tonight in San Francisco

I am looking for a dancing partner/date to a live Argentine Tango music and dancing in San Francisco by Claudio Ortega. It starts at 8pm and my date or partners can pick me up in San Jose.

I do not talk too much but I am not boring during the drive. I only talk about health and finance. I am just kidding. We tease a lot in the Philippines.

It has been a year since I danced Argentine Tango. I love the music including that of the Flamengco, Belly Dance, Reaggae and folk music. I am reminded of the olden times when the speed of activity is slow not fast compared to today. When everyone is in a hurry and panicky when their cell phone is lost or stolen or when the car keys are no where to be found.

In the olden times, when a man takes a woman for dinner he brings corsage of flowers and gifts to the parents. Not anymore now. Most men would prefer meeting a stranger they have not locked eyes with in the internet. Someone who might not share their interests for profiles are written for the reader and not from the heart.

Many years ago men have to write love letters. Ok, enough with my mumblings let us dance already. It is relaxing and soothing to the soul.

Venue:  Community Music Center, San Francisco, 544 Capp St SF

This show brings the intensity and passion of Argentine Tango to the stage. Love, struggle, forbidden passion, exile, separation, desperation, and happiness – all is expressed by music, lyrics, and dance in Noche de Tango!

Claudio Ortega, vocalist
Andrea Monti and Diego Lanau, dancers
Tangonero band, live music

Tickets online: $18  at the door: $20, cash only, subject to availability.

Anti-arthritis oil and balm for sale, first launch

 anti arthritis coconut oil or balm

Dear Friends, 
See you all Sat and Sunday afternoon at my San Jose house to launch my first product, an anti-arthritis balm/oil which can be used internally or externally. It is priced around $50 per 16 oz container.  Your feedback is important to me. I will announce this at my blog today, . It contains turmeric, ginger, coconut oil, grapeseed oil and peppermit essential oil. My curiosity and exposure at Whole Foods created a spark in this product. I also was encouraged to create one as my mom was seeking a massage balm for her arthritis at age 79. I used the oil for my body as massage healing oil to ward off any disease process that might be growing as a result of aging and menopause.
My mom and I tested the product. The original coconut oil was bought at Whole Foods. I am using the same container. I have not yet asked Esther, my artist daughter, for the art cover design. I also plan to sell the formula to Whole Foods and
You may forward  this email to others. Sorry for the short notice. When creativity strikes, you have to capture the moment right away.

Connie Dello Buono