Liver Loving Life

by DanM@cowseatgrass · Published June 23, 2016 · Updated February 27, 2019

When it comes to overall health and metabolic performance, it‘s difficult to overstate the importance of a happy liver, and a regular injection of sugar is critical in more than one way.

It might even be accurate to say that there isn’t really any separation between the idea of a well functioning liver, and efficient metabolic function.

“Non-alcoholic fatty-liver disease (NAFLD), the most common chronic liver disease in affluent societies, is the hepatic manifestation of the metabolic syndrome…lipotoxic by-products of fatty-acid metabolism, such as free fatty acids…accumulate “

When the liver is operating sub-optimally, metabolism is compromised, and vice versa.

One reason for this is that some of the factors which enable the liver to do it’s job properly, also happen to be requirements for a robust and healthy metabolism.

Proper thyroid function is at the top of this list, and the importance of sugar can not be withdrawn from the conversation.

“…thyroid functions in patients with chronic liver diseases were affected by the decrease in serum thyroxine…and impaired peripheral conversion of T4 to T3, the degree of which is in proportion to that of the hepatic dysfunction.”

It doesn’t really matter whether issues begin in the liver and go on to effect overall metabolic function, or whether things interfering with the performance of metabolism, also hinder the liver.

“Thyroid dysfunction may perturb liver function, liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs.”

The truth is that regardless of which direction problems are approached from, improvement in one ‘part’ does not actually happen in isolation from other ‘parts’, and will likely eventually translate into overall improvement.

Take for example a situation where a person is limiting food intake in the name of some kind of cleanse, or fast. After a short amount of time (maybe a day, sometimes much less), once glycogen stores become depleted, cortisol levels tend to increase as part of a process for providing energy via the dissolution of tissue.

The stress from the fast, increases the release of free fatty acids, as another means to providing fuel required by the body. A rise in the release of fat into the bloodstream is known to inhibit thyroid hormone activity, and interfere with glucose uptake by the cell.

A large portion of the conversion of inactive thyroid hormone (T4) into metabolically active thyroid hormone (T3) takes place in the liver, and requires (as part of the process) glucose to be able to enter the liver cells effectively. Fat accumulation in the liver can inhibit this process.

“Alteration in thyroid hormones are seen in critically ill patients admitted to intensive care units….low T3 is an important marker of the severity of the illness and predicts mortality in ICU…”

“Nonalcoholic fatty liver disease (NAFLD) is associated with diminished thyroid action.”

A deficiency of thyroid directly interferes with the storage and release of glycogen in the liver, adding to the circular nature of the problem.

Popular fasts or cleanses are promoted to improve metabolic conditions. Unfortunately, a slowing metabolism, due to stress and insufficient provision of fuel (as well as protein and other requirements), impedes the ability of the liver to do the things required for a return to optimal metabolic function.

In a similar sense, it’s hard for the liver to return to a position where it can properly carry out the functions necessary for improved energy metabolism, in the absence of an initial improvement in overall thyroid performance. Or in other words, what the liver needs to help deal with problems interfering with the liver, is a product of liver function.

This kind of vicious circle or feedback loop is far more difficult to override when the composition of fat released out of storage under stressful conditions, is highly polyunsaturated. This is largely due to the ability of the polyunsaturated fats (PUFAs) to damage the liver, interfere with thyroid function and cause an ongoing inflammatory, blood sugar dysregulated state.

“Unsaturated fatty acids (corn oil, fish oil) exacerbate alcoholic liver injury by accentuating oxidative stress, whereas saturated fatty acids are protective…”

“An excessive accumulation of fat in the liver leads to chronic liver injury such as non-alcoholic fatty liver disease (NAFLD)…Lipid peroxidation products such as hydroxyoctadecadienoic acid and hydroxyeicosatetraenoic acid were increased in the liver…”

The breakdown products of the PUFAs due to lipid peroxidation, promote oxidative stress, and oxidative stress has been shown to be a central factor in liver disease, including NAFLD.

“There was a significant…increase in MDA [malondialdehyde] and GP [glutathione peroxidase] activity (i.e., there is a significant increase in lipid peroxidation rate)…Patients with NAFLD show enhanced oxidative stress…increased MDA could be considered a biochemical marker for lipid peroxidation…”

“The pathophysiology of fatty liver and its progression is influenced by multiple factors… oxidative stress plays a very likely primary role as the starting point of the hepatic and extrahepatic damage.”

“The undeniable role of OS [oxidative stress] in the pathogenesis of NAFLD has been evidenced by the detection of significant increases in markers of oxidative damage of lipids (MDA, 4-HNE)…as has been demonstrated in patients with steatohepatitis…”

Breakdown products of the highly unstable PUFAs also promote insulin resistance, and insulin resistance (associated with a worsening of oxidative stress) is involved in the progression of many kinds of metabolic illness popularly blamed on sugar consumption, including liver disease.

“…insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.”

Liver issues can be explained to be an important factor in the development of degenerative inflammatory disease, including cancer, diabetes, heart disease and Alzheimer’s, and this has a lot to do with the interrelationship between thyroid energy metabolism and liver function, and the stress and inflammation promoting things that have been properly demonstrated to be harmful.

“Insulin resistance might explain the association between NAFLD and cognitive impairment, because insulin resistance plays critical roles in the pathogenesis of NAFLD and Alzheimer disease (AD)…NAFLD might affect cognitive impairment via inflammatory processes…expanded and inflamed liver fat…releases inflammatory cytokines and adipokines, possibly accompanied by…oxidative stress, suggesting that NAFLD is a marker of inflammation…inflammation might be one of the most important causes of degenerative dementia…”

“Non-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular carcinoma (HCC)….This study demonstrated that patients with NAFLD showed a higher association with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NAFLD fibrosis score…showed a strong association with the development of all cancers and HCC.”

“It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.”

A regular influx of tasty, sugary foods (like sweet ripe fruit or juice, for example), can be a potential fix, or way in, reducing stress and helping metabolic energy systems to begin to return to more optimal performance.

“…evidence that higher intake of fructose is not associated with a higher prevalence of NAFLD…Subjects in the highest quartile of fructose intake were 28–44% less likely to have NAFLD than were those in the lowest intake quartile…overfeeding with fructose increased liver fat less than did overfeeding with fat…”

When thyroid metabolism is interfered with, digestive processes tend to slow down, and this is another important part of the inter-related nature of this kind of scenario. Polyunsaturated fats (PUFAs) directly inhibit proper digestive function.

A crucial role performed by the liver involves the detoxification for excretion of toxic substances – released from storage in the fat and muscle, and through the intestines – in order to protect vital organ systems (including the brain), from unnecessary, damaging exposure. The more toxins in circulation – including bacterial endotoxin and breakdown products of PUFAs – the less the effectiveness of detoxification.

“…endotoxin inhibits glucuronidation through an intercellular communication presumably mediated by eicosanoids.”

As digestion slows, more food becomes available to bacteria, eventually causing an increase in the release of bacterial endotoxin, and a subsequent rise in serotonin, nitric oxide, histamine and estrogen in the intestines, and throughout the main system.

All of these substances of stress, when in excess, can directly injure the liver and suppress metabolism.

“Endogenous gut-derived bacterial lipopolysaccharides [endotoxin] have been implicated as important cofactors in the pathogenesis of liver injury…studies have pointed to proinflammatory cytokines such as tumor necrosis factor-alpha as mediators of hepatocyte injury….Kupffer cells are major sources of proinflammatory cytokines…produced in response to lipopolysaccharides.”

“…expression of 5-HT2B is relatively low in healthy liver as compared to diseased liver, in which this receptor is highly expressed in activated HSCs [hepatic stellate cells] in association with fibrotic tissue….HSCs are key suppressors of hepatocyte proliferation…this function is provided by serotonin-induced expression of TGF-β1, dependent on the 5-HT2B receptor…”

“Bacterial infections, including the sepsis syndrome, acutely increase nitric oxide systemically and may lead to acute hepatic dysfunction…”

Potential beneficial effects of a fast or cleanse can arise from the avoidance of harmful polyunsaturated fats (PUFAs) and other metabolically interfering ingredients, leading to an overall reduction in digestive system toxicity and detox load.

Insufficient intake of protein and sugar in particular however, prevents proper thyroid metabolism. This can then slow digestion and decrease intestinal barrier function, allowing more endotoxin and other substances through, placing additional stress on the liver.

An overloaded or damaged liver is less able to carry out its detoxifying role, allowing more and more inflammatory substances – including endotoxin, serotonin, estrogen and cortisol – to pass into circulation. This can counteract benefits which may come from fasting.

“The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification…hepatocytes are involved in the clearance of endotoxin of intestinal derivation…In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis…hepatitis, and primary biliary cirrhosis…”

“With more advanced disease, a progressive fall in testosterone, leutinising hormone and triiodothyronine and a rise in oestradiol was observed. Severity of the liver disease…was the chief determinant of such dysfunctions.”

The stress substances promote inflammation, inadequate thyroid function, as well as blood sugar dysregulation. They encourage the release of cortisol and polyunsaturated free fatty acids, further preventing the liver from doing the things that it needs to do in order to help deal with the same things preventing it from doing what it needs to do…and sometimes it just can’t do it…that was a mouthful!

“…cortisol concentrations strongly correlated to hepatic necroinflammatory grade…and fibrosis stage…among NAFLD [Non Alcoholic Fatty Liver Disease] patients…”

“Chronic inflammation is a major etiologic factor in HCC [Hepatocellular carcinoma]…Higher levels of cortisol…were also confirmed in human pre-HCC and HCC samples…results identify increased cortisol production…in…HCC development…”

“…bioactive lipids derived from oxidized LA are major factors in the progression of steatosis to steatohepatitis, and that they might be helpful in the diagnosis and prognosis of NASH [Nonalcoholic Steatohepatitis]…”

It is the job of the liver to detoxify estrogen so that it can be safely excreted, and increased estrogen can prevent the liver from doing this job effectively. Estrogen interferes with oxidative metabolism and directly inhibits thyroid function, adding weight to the downward spiraling nature of things.

“…estrogen treatment in vivo sensitizes Kupffer cells to LPS [lipopolysaccharide], leading to increased toxic mediator production by the liver.”

“…a deficiency of the vitamin B complex decreased the ability of the liver to inactivate estrone and a-estradiol…the addition of thiamine and riboflavin restored the ability of the liver to inactivate these substances.”

“We have studied a group of individuals with cirrhosis from various causes and have found that, irrespective of cause, there appears to be an increase in the production of estrogen…”

“…cirrhosis…is characterized by the reciprocal relationship between decreased 2-hydroxylation and increased 16α-hydroxylation previously described in hypothyroidism…Demonstration of abnormal peripheral metabolism of estrogen…”

I’m not a doctor, and this is not intended as medical advice, but I have seen enough evidence to be convinced that when a genuine holistic approach is taken, figuring out ways to achieve an improvement in metabolism (in order to increase healing, regenerative and protective capacity) does not necessarily require specific diagnostic precision.

Symptoms can usually be approached from the perspective of an attempt to reduce inflammation, improve digestion and liver function, or simply by looking closely at thyroid metabolism. Any or all of these solutions have been shown to be effective, and are likely to be beneficial in almost every situation.

Is it possible to reduce exposure to the more highly unsaturated fats? How much protein is required and what is the source? Are mineral and vitamin needs being met? Can stress be reduced? Are nutritional requirements able to be met whilst minimizing digestive issues?

Closely tied to the above questions, is the importance of maintaining glycogen stores, via the provision of easily assimilable sugar sources. This provides fuel to energize the liver, enabling it to do the jobs it is designed to do (in relation to detoxification and metabolic function), helping to keep stress and inflammatory issues at bay.

Contrary to popular anti-sugar hype, sugar from fruit or simply white sugar, in the appropriate context, is a metabolism enhancing, liver energizing, thyroid promoting substance.

Fructose powerfully stimulates the storage of glycogen, and any excess not burned (often very little because of the metabolism stimulating effect of sugar) is converted into anti-inflammatory and protective saturated fats.

The ability of the body to convert excess sugar into triglycerides – as saturated fats, for storage in the tissues – is another part of the liver’s anti-stress, pro-metabolic function.

Apart from sugar and thyroid, things such as the B vitamins, Selenium, and sufficient protein are also important for ensuring the liver is properly enlivened.

The best kind of ‘cleanse’, is that which happens from moment to moment, when the cleansing organ – the liver – is properly fueled and allowed to do its job.

This likely cannot occur in an optimal fashion, when stress substances are high, blood sugar is dysregulated, digestion is slow, and metabolism is suppressed, and as such, these issues are important to consider. The liver isn’t a separate organ that functions independently of the whole. In terms of the operation of metabolism, no system works in isolation.

But regardless, it still makes sense, when facing metabolic illness, to try to deal with some of the things (like PUFAs or endotoxin, for instance) which are interfering with liver function, before attempting to up-regulate metabolism too quickly and too much, as this can end up adding to stress levels, rather than the intended opposite.

Coffee or caffeine has proven to have a great many liver protective effects although a stressed system and damaged liver can be initially quite sensitive to consumption, especially when taken with insufficient sugar.

“…caffeine has anticancer effects…caffeine could inhibit the proliferation, migration and invasion significantly at physiologically applicable concentration in vitro…This makes caffeine a potential candidate for treating HCC [liver cancer]…”

“CBT [caffeine breath test] can be an easy to use, safe, non-invasive method for the evaluation of liver function impairment…”

Some other things which have been shown to help the liver perform better include aspirin, cyproheptadine and famotidine, niacinamide, methylene blue, glycine, thiamine, vitamin E, taurine, pregnenolone, well cooked mushrooms, a daily raw carrot, activated charcoal and certain antibiotics.

A diet avoiding the PUFAs and limiting difficult to digest fibrous and starchy carbohydrates, getting enough protein and nutrients from milk, cheese, or gelatinous meat, and plenty of sugar from sweet ripe juicy fruits, fruit juice, honey and white sugar, is one possible approach to improving the state of the liver, helping it to do what it does best.