Beware When Rousing The Bear With Aspirin
Although in one sense as humans we don’t exactly hibernate, from another perspective chronic stress (often provoked or exacerbated by inadequate fuel accessability), can encourage a hypometabolic state biologically similar to torpor, as a kind of defensive strategy for damage control.
“Under conditions when metabolic supply is acutely or chronically reduced to critical levels, non-hibernating mammals can also invoke protective phenotypes that share some characteristics with torpor…”
“Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism….our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.”
Whenever conditions are trying and stress is ongoing – with glycogen stores running low and enough fuel not available – metabolic systems can slow to prevent rapid catabolization and self destruction.
If, under chronically stressful circumstances, energy needs were not at some point reduced, one possible scenario would be that cortisol (converting muscle and other valuable tissue as a secondary means to providing fuel), might be given the chance to eat through a large portion of the body, causing organ damage or even death.
“…hypometabolism is typically recruited by resilient organisms to withstand and recover from otherwise life-threatening hazards…Through the coordinated down-regulation of biosynthetic, proliferative and electrogenic expenditures at times when little ATP can be generated, a metabolism turned ‘down to the pilot light’ allows the re-balancing of energy demand with supply at a greatly suppressed level…”
“During starvation, glucose production is carried out by using the protein storage. The proteolysis in this period mainly takes place in skeletal muscle, however, protein degradation is also observed in solid organs. Administration of glucose to surgical patients during fasting aims to reduce proteolysis and to prevent the loss of muscle mass.”
“…hypothyroidism, reduced thyroid hormone levels, is associated with hypometabolism characterized by reduced resting energy expenditure, weight gain, increased cholesterol levels, reduced lipolysis, and reduced gluconeogenesis.”
“There is a blunted hypothalamo-pituitary-adrenal response to hypoglycemia in hypothyroid persons…The role of gluconeogenesis is reduced in hypothyroidism, both in skeletal muscle and in adipose tissue.”
Even though from a survival perspective, the ability to turn down energy requirements is an important mechanism for protection against malnutrition and starvation (and other difficult conditions), from the point of view of metabolic function, it isn’t always optimal. When metabolism is chronically suppressed, cellular performance, immune function and overall regenerative and disease protective capacity can be compromised.
Many of the symptoms associated with the onset of degenerative conditions like diabetes – including insulin resistance, reduced glucose oxidation capability, increased amounts of free fatty acids in the blood and inflammation – are connected with a kind of stress induced, metabolically suppressed, hibernation like state.
“Thyroid hormone is a major regulator of metabolism and energy expenditure…Overt and subclinical hypothyroidism are associated with a decreased insulin sensitivity and glucose tolerance, partially due to a decreased ability of insulin to increase glucose utilization mainly in muscle… low and low-normal thyroid function are related to an increased risk of diabetes.”
“Stress responses include activation of the sympathetic nervous system and stimulation of epinephrine and cortisol release. These hormones may over the long term reduce insulin sensitivity. Cortisol may also favour the development of central obesity.”
“We investigated whether…11β-HSD1 [an enzyme activating cortisol]…expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction…11β-Hsd1 was higher in adipose tissues…increased 11β-HSD1 expression contributes to reduced mitochondrial respiration…”
“This study aimed at evaluating whether thyroid hormone treatment could improve glycaemia and insulin response…T3 treatment reduces glycaemia and improves insulin sensitivity…part of this effect could result from its negative modulation of inflammatory cytokine expression.”
Free fatty acids (released in greater quantity when stress is high and sugar is unavailable or inaccessible) have been shown to be increasingly more anti-metabolic and harmful, relative to how polyunsaturated they become.
As well as being powerfully metabolism and thyroid suppressing, the polyunsaturated fats (PUFAs) are known to be a significant cause of inflammation and insulin ineffectiveness or insufficiency. Excessive exposure is capable of leading to a chronic inability of cells to be able to properly utilize available blood sugar supplies.
“HFDs [high fat diets] in…insulin-sensitive humans…were associated with reduction in…oxidative capacity…These studies implicate increased dietary fat in diabetes and the prediabetic/insulin-resistant state.”
Symptoms of depression (and other mood related disorders) have been shown to arise in association with a torpor-like hypo-metabolic state, and often go hand in hand with biochemical changes which lead to diabetes, including blood sugar and insulin issues, and increased exposure to the inflammatory breakdown products of PUFAs.
“Metabolic depression…for energy preservation, is responsible for torpor, hibernation…is the process underlying the…hypometabolism…neurobiological changes and vegetative symptoms of major depression in humans….Hibernation in bears and major depression…are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and…neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol…low respiratory quotient; oxidative stress response…”
Aspirin has proven to be useful in the reduction of many of the above issues of suppressed metabolism, including inflammation, blood sugar dysregulation and insulin dysfunction. In terms of thyroid metabolism and health in general, this can all have the potential to be quite positive, increasing protective capacity and regenerative capability. Aspirin has been effective in the treatment of both diabetes and depression.
“Aspirin is a unique nonsteroidal anti-inflammatory drug; at high doses (aspirin(high), 1g), it is anti-inflammatory stemming from the inhibition of cyclooxygenase and proinflammatory signaling pathways including NF-kappaB, but is cardioprotective at lower doses (aspirin(low), 75 mg)…we suggest that aspirin(low) possesses the ability to inhibit mammalian innate immune-mediated responses…a new approach to treating inflammation-driven diseases.”
“…results identify a novel mechanism by which salicylates may enhance insulin action in diet-induced obesity, involving downregulation of adipose 11β-HSD1 expression…findings suggest that the anti-inflammatory agent salsalate alters glucocorticoid metabolism in…humans “
“Insulin resistance is a central feature of type 2 diabetes…We…investigated whether salicylates reduce lipid-induced insulin resistance in humans by affecting inflammatory pathways…ASA pretreatment attenuated lipid-induced insulin resistance in healthy humans…”
“Accumulating data advocates that inflammatory mediators may contribute to depression in experimental models as well as in humans…Our results suggest that aspirin can serve as a potential antidepressant both individually and as adjuvant agent in the treatment of depression.”
Aspirin can not only reduce cortisol levels, and help move cells away from using fat as a fuel source and towards the oxidation of glucose, it can also protect against the highly inflammatory, thyroid interfering PUFAs, and their release as free fatty acids into circulation.
“Aspirin therapy…resulted in significant reductions in both fasting and postprandial plasma fatty acid concentration, and such reductions can…contribute to enhanced insulin action…aspirin treatment improved both fasting and postprandial hyperglycemia in patients with type 2 diabetes…”
“…a 2-week trial of high-dose aspirin treatment was accompanied by significant decreases in hepatic glucose production (22%), fasting plasma glucose (24%), fatty acids (50%), and triglycerides (48%) and a 19% increase in peripheral glucose disposal.”
Taken together, these as well as other stress reducing redirections (from aspirin use), can lead to a significantly higher functioning metabolism, with the potential for improvements in all biological systems, and a reduction of symptoms of degenerative conditions.
“…aspirin-afforded neuroprotection occurred in parallel with a lesser decrease in ATP levels…Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase in NADH-dependent respiration…findings show a novel mechanism for the neuroprotective effects of aspirin…useful in the management of patients with high risk of ischemic events.”
“ASA [aspirin] treatment effectively attenuated MCT-induced pulmonary hypertension, right ventricular hypertrophy, and occlusion of the pulmonary arteries. The effects of ASA was associated with a reduction of 5-HT [serotonin].”
Rising levels of serotonin, estrogen and nitric oxide (due to stress, metabolic suppression and inflammation), interfere with oxidative metabolism, and encourage hibernation or hibernation-like reactions. Stress reduction with the use of aspirin, can have a powerful impact upon metabolic performance, and this can create a change in fuel (and other nutritional) requirements.
“Chronic widespread stress-induced serotonergic overdrive in the cerebral cortex in schizophrenia…is the basic cause of the disease…serotonergic overdrive leads to neuronal hypometabolism and ultimately synaptic atrophy and grey matter loss…Frontal lobe hibernation causes negative symptoms and cognitive impairment.”
“Frequency of use of…aspirin…was inversely associated with concentrations of estradiol…free estradiol…estrone sulfate…and the ratio of estradiol to testosterone…Among postmenopausal women, regular users of aspirin…may have lower estrogen levels than non-users…”
“…stress exposure…caused brain expression of iNOS, an increase in plasma glutamate and brain TNF-alpha, induction of oxidative indicators in brain and a fall in brain ATP levels….aspirin…inhibited all these effects caused by stress…”
Stress and the suppression of metabolic function can inhibit digestion and promote exposure to bacterial endotoxin, which further interferes with energy metabolism and blood sugar regulation, directly and indirectly increasing levels of the inflammatory and energy system suppressive stress substances, serotonin and nitric oxide.
Apart from promoting diabetes and mood dysregulation, endotoxin, serotonin and nitric oxide have been shown to encourage the onset of migraine headaches. Hypoglycemia and other blood sugar related issues have also been associated with symptoms of migraine.
The fact that aspirin is protective against migraine, as well as diabetes and depression, and the fact that aspirin helps to lower excessive levels of the stress substances (including serotonin, endotoxin and nitric oxide) associated with all of these conditions, is probably not a coincidence. There are many ways that aspirin can be seen to improve the function of metabolism.
As cellular performance is enhanced, and metabolism is up-regulated, energy requirements can go up significantly, bringing with it an escalating demand for a variety of nutrients, and an increased need for the provision of sugar.
“Glucose oxidation rates improved significantly following 2 weeks of aspirin therapy…high-dose aspirin may…have an insulin-sensitizing effect or a direct antilipolytic effect on adipocytes, leading to reduced rates of lipolysis and lower plasma fatty acid levels…”
When you wake the Bear, you want to make sure there is plenty of fuel available.
If fuel isn’t provided, the response can be an increase in stress, which may then instigate reactions which can end up being counter-productive. For this reason, it makes sense, if you are using aspirin, to combine it with a decent source of sugar.
Speeding up energy metabolism via any means without sufficient supply of sugar for fuel, can lead to further depletion of potentially already low glycogen stores, and this can eventually lead to rising levels of cortisol and adrenalin and other inflammatory stress substances.
“…elevated concentrations of glucocorticoids such as cortisol stimulate catabolism to ensure fuel…sugar may provide the fuel needed to meet the energetic demands of stress, which may reduce the need for glucocorticoid-driven energy catabolism and mobilization of the body’s energy stores…results provide…evidence in humans for a physiological link between sugar consumption and cortisol reactivity to stress.”
Some things other than aspirin, that are known to be able to have a similar effect on metabolism – potentially increasing fuel and other nutritional requirements – include thyroid hormone, caffeine, red light, salt, protein, pregnenolone, progesterone, niacinamide (B3), even sugar itself.
In a roundabout way, promoting metabolic function, without meeting the needs which tend to increase as a result, can potentially create more stress, and lead to an eventual overall worsening of metabolic performance.
Wastage of valuable tissue due to high cortisol, an increase in inflammatory anti-metabolic substances (such as serotonin, nitric oxide and estrogen), and rising free fatty acid release, can occur as a result of insufficient fuel supply. All these and other potentially damaging effects of stress, can end up being heightened by aspirin use, even though they are things that aspirin can be used to protect against.
Of course this is a matter of context, and not a black and white thing. Reactions may vary, and many will still benefit from aspirin use regardless of whether they have an understanding of the intricacies of metabolic fueling, or whether enough fuel is made available. I’m not a doctor or a scientist, and none of this is intended as advice. It’s simply one perspective to consider, or not.
The flip side of all of this, is that improvements in overall performance from aspirin use, can also mean that some nutritional requirements are reduced, because of resultant rising efficiency and effectiveness of metabolic function. For instance, improving thyroid metabolism can have the effect of promoting the ability to store glycogen in the liver, as well as the ability to use it more economically.
Appropriate fueling quite possibly can become a more immediate issue, when the dose of aspirin being taken is in the high range. Regardless, underestimating fuel needs (and ignoring factors which can interfere with the ability of cells to use sugar) can have an effect on results of the use of aspirin (and other pro-metabolism things), and no two people are in the exact same metabolic condition.
One feasible approach to providing nutritional and fuel requirements for an improving metabolism, is a diet with enough protein from milk, cheese and gelatin, and plenty of sugar from sweet ripe juicy fruits, fruit juice, honey and white sugar.
Making changes gradually, and keeping a close eye on symptom variations can increase chances of success. As always, tracking before and after (breakfast or lunch) resting pulse and temperature readings, can be very instructive and can help remove much of the confusion.
By all means wake the Bear, but don’t be left standing there with nothing but yourself to offer. Because sometimes you feed the Bear, and sometimes the Bear feeds on you.
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