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Kidney damage and the role of glyphosate

The domestic pig (Sus scrofa) is an essential animal as a biomedical model because it is similar to humans in size, anatomy, physiology, metabolism, pathology and pharmacology. Alan Archibald (Professor of Medicine and Veterinary Science at the University of Edinburgh) believes that human studies in pigs give the best results (Alan Archibald et al. 2020).

Table of Contents

Diseases of the liver and kidneys – genetically modified plants

From 1995 to 2011, our product developer worked daily supervising a livestock farm producing between 7 and 12 thousand pigs per year. During this time, he continuously monitored the condition of the animals. 

From 2005 onwards, his observations showed a steady deterioration in the state of the two central metabolic organs of the pigs, the liver and the kidneys. This was demonstrated by the changes in the condition of the organs examined during the autopsies. More and more small pigs were born due to the state of two vital organs, the liver and the kidneys. By 2007, this trend had increased. 

After 2011, were surveyed other pig farms in Europe for four years. The study aimed to confirm the deterioration in the health of pigs. It became clear that the problem is present in most countries, with varying degrees of severity.

Evidence of chronic liver problems

We confirmed the liver problems by blood tests carried out on several farms. The symptoms were also visible. On some farms, piglets, fatteners, and sows have a mass of yellowish eyelids. At this time, the bilirubin level in the blood is already very high due to liver inflammation. Light-coloured faeces accompany this phenomenon.

The fluid space of the inflamed liver cells increases, causing them to swell and block the intrahepatic bile ducts. It prevents bile from entering the gallbladder. Therefore, the bile cannot be excreted into the intestine, and the efficiency of fat digestion is impaired.

A critical function of the liver is hormone production. When hormone production is not correct, carbohydrate metabolism and the synthesis of glucocorticoids (which play a role in hormonal regulation) are also damaged.

Glyphosate-resistant genetically modified soy – how did it get here?

To understand the history and effects of genetically modified crops, we need to look back a little. In 1996, the US Food and Drug Administration approved cultivating glyphosate-resistant genetically modified soy. (The active ingredient glyphosate is a so-called total herbicide. It is widely used in agriculture under several brand names: Roundup Ultra®, Roundup Pro®, Accord®, Honcho®, Pondmaster®, Protocol®, Rascal®, Expedite®, Ranger®, Bronco®, Campain®, Landmaster®, Fallow Master®, Glyphomax®, Glypro®, Silhouette®, Rattler®, MirageR®, JuryR®, Touchdown®, Rodeo®, Aquamaster®).

Genetically modified soybeans do not produce more and are not more disease-resistant. It is more susceptible to fungi, is not more drought tolerant and does not contain more nutrients than its non-GM version. However, it is resistant to herbicide treatment.

Food intended for human consumption in Europe is free from genetically modified plants or derivatives. However, this restriction does not apply to livestock farms, so cheap, genetically modified soya is an animal feed staple. Thus, GM crops and glyphosate still indirectly affect many foods for human consumption.

Biochemical background to genetic modification

In flowering plants, fungi, and many bacteria, amino acids with aromatic side chains are synthesised by the shikimate pathway. Glyphosate blocks the activity of the enzyme EPSP and kills the plant. 

In glyphosate-resistant soybeans, genetic modification results in a modified enzyme. The CP4 EPSP synthetase enzyme from the bacterium Agrobacterium tumefaciens converts the shikimic acid. The formation of aromatic side-chain amino acids in GMO soy is thus solved. Spraying kills all other plants except the GM soybean.

Genetic modification and changes in the residual value of glyphosate

Over the last 20 years, the maximum residue limit for glyphosate has been significantly increased in both food and feed. This trend is also prevalent in Europe and America. The first increase from 0.1 mg/kg to 20 mg/kg was in 1999. In the USA, the limit was raised even further from 20 mg/kg to 40 mg/kg in 2014.
In many cases, they cannot even comply with the permitted limit. The Plant Health Authority of the Danish Ministry of Agriculture and Fisheries has tested extracted soybean meal imported from the Americas. In 3 out of 4 samples, the glyphosate content was higher than the permitted 20 mg/kg. The test material is available here.

Why can glyphosate residues in humans or animals cause problems?

The previous position was that glyphosate has no direct adverse effect on mammals. However, this has now been overturned after glyphosate was shown to inhibit the function of the cytochrome P450 enzyme group. This enzyme system catalyses more than 60 biochemical reactions in the endoplasmic reticulum of the liver. It plays an essential role in the degradation of xenobiotics (artificial chemicals). This enzyme system degrades more than 650 xenobiotic substrates. Its normal function is of enormous importance.

The cytochrome P450 enzyme system and its function

In the 1960s, the pharmaceutical industry discovered that cytochrome P450 enzymes play a crucial role in absorbing drugs in the body. (In the last few years, knowledge of the cytochrome P450 superfamily of heme-containing monooxygenase enzymes increased significantly). By 1995, 481 different P450 enzymes had been identified for the whole world.

The cytochrome P450 enzymes are mainly present in the endoplasmic reticulum of hepatocytes in the liver, small intestinal enterocytes, and smaller amounts in the kidney, lung, and brain. Cytochrome P450 enzymes catalyse the conversion of more than 60 endogenous substrates in the mammalian body. They are involved in the metabolism of prostaglandins, fatty acids, steroid hormones, vitamin D leukotrienes (local hormones), etc. The cytochrome P450 system is crucial in degrading and detoxifying toxic substances and artificial xenobiotics.

The key to effective detoxification

The enzymes make the substrate molecule in the active centre of P450 more water-soluble so that the body can eliminate it more easily. The activity of the P450 enzymes is not constant within the body. Xenobiotics or specific endogenous regulatory molecules introduced into the body can increase (inducers) or decrease (inhibitors) the activity of the P450 enzymes.

There is evidence that glyphosate is a xenobiotic that can inhibit the activity of cytochrome P450 enzymes. The problem is serious since it causes a toxic effect on the body and reduces the detoxification of all other xenobiotics. It decreases the body’s tolerance to mycotoxins.

Hepatotoxicity of glyphosate

Several researchers have described the hepatotoxic effects of glyphosate in mammals, leading directly to liver disease. Even at low concentrations, glyphosate affects the liver (Benedetti et al. 2004).

Séralini and colleagues (2011) conducted a 90-day feeding trial in mammals. They found that GMO crops caused chronic toxicosis in both the liver and kidneys of the animals.

In an experiment by J.A. Carmen et al. (2013), female animals raised on GMO soy and maise diets had a 25% greater uterine mass than pigs raised on non-GMO diets. The animals showed endometrial hyperplasia and endometriosis. This is due to high levels of the hormone estrogen combined with low levels of progesterone and the impaired function of cytochrome enzymes (they should break down estrogen).

Kidney problems in farm workers

The kidney-damaging effects of glyphosate have been observed in young agricultural workers in India, Sri Lanka and Central America. An unexplained chronic kidney disease (CKD) has emerged in the last decade and a half. So far, more than 20,000 people have died from the mysterious illness. 

Since 2007 the number of patients from this population requiring kidney dialysis has been steadily increasing. The suspected cause is the increased use of glyphosate and the high levels of arsenic and cadmium in the water in the region. 

Since glyphosate also readily forms chelates with heavy metals, the researchers suspect the cause of the problem is the kidney-damaging effects of glyphosate and heavy metal chelates.

Kidney problems in animals

Chronic kidney failure is significant in pig herds. In normal functioning, creatinine and urea are excreted from the blood by the kidneys. When kidney function is slowed or impaired, creatinine and urea levels in the blood elevate. When healthy, the urine of pigs does not contain bilirubin. If bilirubin is detected, it is probably due to a liver function problem.

As a consequence of the toxic effect, the liver is damaged. In the case of diffuse vacuolation, swollen liver cells compress the intrahepatic capillaries, causing them to become blocked. The liver produces bile, which cannot be excreted into the intestine. Bilirubin is then discharged into the bloodstream. 

The kidneys excrete bilirubin in the blood. The appearance of urobilinogen in the urine already indicates a liver and kidney problem. The appearance of ketone bodies in the urine and a urine pH between 5.0 and 6.0 is a consequence of uncompensated acidosis.

Healthy (good renal function, ketosis-free carbohydrate metabolism, efficient circulation and respiration) sows have a urine pH of 7.0-7.5. If the sows’ feed does not contain animal protein, the pH is higher, assuming a healthy animal, is at 7.5 pH. In chronic renal failure, it does. 
There may be actual protein urination, in which case the protein comes from plasma protein in the blood. There may be protein of non-renal origin in the urine. In this case, epithelial cells detached from the walls of the lower urinary tract after the kidney is passed into the urine (due to disease of the lower urinary tract). Inflammatory disease of the lower urinary tract can be ruled out without nitrite in the urine. Nitrite is also present in the urine in the case of bacterial urinary tract infection.

In the last 10 to 15 years, we have seen several external lesions and phenomena in breeding sows that were not seen before the turn of the millennium. These phenomena result from hepato-renal physiological problems that affect the vitality and quantity of reproduction.

Where do we look for a solution?

In formulating Fulvicherb-Synergy, we have turned to nature: milk thistle is one of the most potent detoxifiers. Its action is due to the flavonolignan complex in its fruit, known as silymarin. The substances in the silymarin complex bind effectively to liver cells, preventing toxins from entering the liver. The neutralising effect of silymarin enables liver cells to fight xenobiotics and biogenic amines more effectively. 

The silymarin complex has a protective effect on cytochrome p450 enzymes.

Oral administration of silymarin has a marked effect on liver injury. It reduces lipid peroxidation and increases antioxidant enzyme activity to enhance the antioxidant defence system of the liver. Reduces the overexpression of proinflammatory cytokines, inhibits inflammatory signalling and improves liver vitality. The liver enzymes ALT, AST, ALP and GGTA in blood serum improve by silymarin action.

Antioxidant enzyme levels (catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase) increase dramatically using silymarin (Lan Wang et al. 2017).

Silymarin concentrates in kidney cells and promotes regeneration processes in the epithelial cells of the renal tubule. Silymarin protects animals and humans from toxic kidney damage (Barbara L et al. 2008).

How we can harness the power of nature

The active ingredient in milk thistle has a fundamentally poor utilisation rate. It is insoluble in water, limiting its use internally and externally. In experiments on rats, only 0.95% of the amount of silibinin administered orally is utilised (Jhy-Wen Wu et al. 2007).

Fulvicherb – Synergy contains a complex of silymarin absorption enhancers, and provides a 4.6 to 10-fold absorption according to various literature sources. The effect enhancers and adjuvants such as taxifolin, quercetin, kaempferol, and apigenin (with different polarity properties) synergise the silymarin-type active ingredients of the flavonolignan complex. 

The fruit of the milk thistle contains sterols and active substances with “amphiphilic” (dual) properties. They have a polar and an apolar moiety and contain a lipid-soluble and a water-soluble moiety. Both polarity moieties are readily soluble in organic solvents (Kidd P, Head K. 2010).

The extraction technology for the active substances we use is unique. In addition to cold-pressed oil, we use cold-pressed, tinctured cake to extract active ingredients with different polarity properties. We add a natural amphiphilic substance to aid the absorption of the active ingredients. The result is good absorption and excellent silymarin action.

The adverse effects of glyphosate are challenging to avoid in our modern world. Fulvicherb – Synergy is a unique formulation that helps to detoxify the body, in addition to foods from suitable sources.

Read the article in German: Glyphosat und Nierenschaden – eine mögliche Ursache

Read the article in Polish: Co wspólnego mają świnie i ludzie


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