Glyphosate and kidney damage - a possible cause

The domestic pig (Sus scrofa) is an indispensable animal as a biomedical model, as 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 are best conducted in pigs (Alan Archibald et al. 2020).

Kidney damage - genetically modified plants

From 1995 to 2011, our product developer worked daily on a breeding farm that produced between 7 and 12 thousand pigs per year. During this time, he constantly monitored the health of the animals.

From 2005 onwards, his observations showed a steady deterioration in the condition of the two central metabolic organs of the pigs, the liver and the kidneys. This was reflected in the changes in the condition of the organs that were examined during the necropsies. The condition of the two vital organs, the liver and kidneys, led to more and more small piglets being born. By 2007, this trend had intensified.

From 2011, further pig farms in Europe were investigated for four years. The aim of the study was to confirm the deterioration in pig health. It became clear that the problem exists in most countries, albeit to varying degrees.

Detection of chronic liver problems

We confirmed the liver problems through blood tests carried out at several farms. The symptoms were also visible. On some farms, piglets, fattening pigs and sows have masses of yellowish eyelids. At this point, the bilirubin level in the blood is already very high due to the liver inflammation. Light-coloured faeces are the accompanying symptom.

The fluid space of the inflamed liver cells enlarges, causing them to swell and block the intrahepatic bile ducts. As a result, the bile cannot enter the gallbladder. As a result, the bile cannot be excreted into the intestine and fat digestion is impaired. As the bile pigment (bilirubin) does not colour the stool dark, most people have yellowish diarrhoea.

An important function of the Liver is the production of hormones. If hormone production does not function properly, carbohydrate metabolism and the synthesis of glucocorticoids (which play a role in hormone regulation) are also impaired.

Glyphosate-resistant genetically modified soya

To understand the history and impact of genetically modified crops, we need to look back a little. In 1996, the US Food and Drug Administration authorised the cultivation of glyphosate-resistant genetically modified soybeans. (The active ingredient Glyphosate is a so-called total herbicide. It is used in agriculture under various 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 soya beans do not produce more and are not more resistant to disease. It is more susceptible to fungal attack, is not more drought-resistant and does not contain more nutrients than its non-GM variant. However, it is resistant to herbicide treatments.

Food intended for human consumption in Europe must not contain genetically modified plants or their derivatives. However, this restriction does not apply to livestock farming, which means that cheap GM soya is a staple food. Genetically modified plants and glyphosate therefore continue to have an indirect impact on many foods intended for human consumption.

Biochemical background of genetic engineering

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

In glyphosate-resistant soya beans, the genetic modification leads to an altered enzyme. The enzyme CP4 EPSP synthetase from the bacterium Agrobacterium tumefaciens converts shikimic acid. This prevents the formation of aromatic side-chain amino acids in GM soya. Spraying kills all plants other than the GM soya bean.

Change in the maximum residue level for glyphosate

In the last 20 years, the maximum residue levels for glyphosate in both food and animal feed have been significantly increased. This trend is also prevalent in Europe and America. The first increase from 0.1 mg/kg to 20 mg/kg took place 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 Protection Agency of the Danish Ministry of Agriculture and Fisheries has tested soya extraction meal imported from America. In 3 out of 4 samples, the glyphosate content was higher than the permitted 20 mg/kg. The test material is available here.

Why do glyphosate residues endanger humans and animals?

It used to be said that glyphosate had no direct harmful effects on mammals. However, this was refuted after it was proven that glyphosate inhibits the function of the enzyme group cytochrome P450. This enzyme system catalyses more than 60 biochemical reactions in the endoplasmic reticulum of the liver. It plays an important role in the degradation of xenobiotics (artificial chemicals). This enzyme system degrades more than 650 xenobiotic substrates. Its normal function is of great 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 the absorption of drugs into the body. (In recent years, knowledge of the cytochrome P450 superfamily of haem-containing monooxygenase enzymes has expanded considerably). By 1995, 481 different P450 enzymes had been identified in all living organisms.

Cytochrome P450 enzymes are mainly found in the endoplasmic reticulum of hepatocytes in the liver and in the enterocytes of the small intestine, and in smaller quantities in the kidneys, lungs and brain. Cytochrome P450 enzymes catalyse the conversion of more than 60 endogenous substrates in the body of mammals. Among other things, they are involved in the metabolism of prostaglandins, fatty acids, steroid hormones, vitamin D and leukotrienes (local hormones). The cytochrome P450 system is crucial for the degradation and detoxification of toxic substances and artificial foreign substances.

Detoxification and kidney damage

The enzymes make the substrate molecule in the active centre of P450 more water-soluble so that the body can excrete it more easily. The activity of the P450 enzymes is not constant in the body. Xenobiotics or certain endogenous regulatory molecules that enter 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. This is a serious problem as it has a toxic effect on the body and reduces the detoxification of all other xenobiotics. It reduces the body's tolerance to mycotoxins.

Glyphosate worsens the Liver function

Several researchers have described hepatotoxic effects of glyphosate in mammals that lead directly to liver disease. Even in low concentrations, glyphosate has an effect on the liver (Benedetti et al. 2004).

Séralini and colleagues (2011) carried out a 90-day feeding trial on mammals. They found that GM plants caused chronic toxicity in both the liver and kidneys of the animals.

In an experiment by J.A. Carmen et al. (2013), female pigs fed GM soya and GM maize had a uterine mass 25 % larger than pigs fed non-GM feed. The animals showed hyperplasia of the uterine mucosa and endometriosis. This is attributed to the high oestrogen content in combination with a low progesterone level and a disturbed function of the cytochrome enzymes (which are supposed to break down oestrogen).

Kidney damage in agricultural workers

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

The number of dialysis patients in this population group has been rising continuously since 2007. The increased use of glyphosate and the high levels of arsenic and cadmium in the region's water are thought to be the cause.

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

Kidney damage in animals

Chronic renal insufficiency is of great importance in pig herds. With normal Kidney function creatinine and urea are excreted from the blood via the kidneys. If kidney function is slowed down or impaired, the creatinine and urea levels in the blood rise. The urine of healthy pigs does not contain bilirubin. If bilirubin is detected, this is probably due to impaired liver function.

The liver is damaged as a result of the toxic effect. During diffuse vacuolisation, swollen liver cells compress the intrahepatic capillaries and block them. The liver produces bile that cannot be excreted into the intestine. The bilirubin is then excreted into the bloodstream.

The kidneys excrete the bilirubin with the blood. The presence of urobilinogen in the urine already indicates liver and kidney disease. The appearance of ketone bodies in the urine and a urine pH value between 5.0 and 6.0 are the result of uncompensated acidosis.

Healthy sows (good kidney function, ketosis-free carbohydrate metabolism, efficient circulation and respiration) have a urine pH value between 7.0 and 7.5. If the sow's feed contains no animal protein, the urine pH value of a healthy animal is higher at 7.5. It is higher in the case of chronic renal insufficiency.
Protein may be present in the urine, in which case the protein comes from the plasma protein in the blood. However, there may also be protein in the urine that does not originate from the kidneys. In this case, epithelial cells have detached from the walls of the lower urinary tract after the urine has been excreted from the kidneys (due to a disease of the lower urinary tract). An inflammatory disease of the lower urinary tract can be ruled out without nitrite in the urine. Nitrite is also found in the urine in bacterial urinary tract infections.

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

Where do we look for solutions against kidney damage?

During the development of Fulvicherb-Synergy with Fulvic acid we have been inspired by nature: The Milk thistle is one of the most powerful detoxifying agents. Its effect is based on the flavonolignan complex contained in its fruits, which is known as silymarin. The substances of the silymarin complex bind effectively to the liver cells and thus prevent toxins from entering the liver. The neutralising effect of silymarin enables the liver cells to fight xenobiotics and biogenic amines more effectively.

Against kidney damage with silymarin complex from milk thistle

The oral administration of silymarin has a significant effect on liver damage. It reduces lipid peroxidation and increases the activity of antioxidant enzymes, thereby strengthening the liver's antioxidant defence system. It reduces the overexpression of pro-inflammatory cytokines, inhibits inflammatory signals and improves liver vitality. The liver enzymes ALT, AST, ALP and GGTA in the blood serum are improved by the effect of silymarin.

The levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase) increase dramatically with silymarin (Lan Wang et al. 2017).

Silymarin accumulates in the 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).

The active ingredient contained in milk thistle is generally poorly utilisable. It is insoluble in water, which limits its internal and external use. In experiments with rats, only 0.95 % of the orally administered amount of silibinin was utilised (Jhy-Wen Wu et al. 2007).

Fulvicherb - Synergy contains a complex of silymarin absorption enhancers which, according to various literature sources, enables a 4.6 to 10-fold absorption. The active enhancers and excipients such as taxifolin, quercetin, kaempferol and apigenin (with different polarity) act synergistically with the silymarin active ingredients of the flavonolignan complex.

The fruits of milk thistle contain sterols and active ingredients with "amphiphilic" (dual) properties. They have a polar and a non-polar part and contain a lipid-soluble and a water-soluble part. Both polar parts are readily soluble in organic solvents (Kidd P, Head K. 2010).

The extraction technology of the active ingredients we use is unique. In addition to cold-pressed oils, we use cold-pressed tinctures to extract active ingredients with different polarity properties. We add a natural amphiphilic substance to promote the absorption of the active ingredients. The result is good absorption and an excellent effect of silymarin.

The negative effects of glyphosate are difficult to avoid in our modern world. Fulvicherb - Synergy is a unique formula that helps detoxify the body in addition to food from appropriate sources.