Heavy metals, oxidation and nitrosative stress

Reactive oxygen and nitrogen species arise in normal metabolism. Only when the protective side can no longer keep up do they attack membranes, proteins and DNA. Metals bind to the same sulphur groups the protective side relies on — which is why both topics sit together here.

We measure mostly from urine: 8-OHdG for oxidised DNA, plus citrulline, methylmalonic acid and nitrophenylacetic acid for the nitrogen axis.

Analysen

What is measured here

10 Analysen · €45 bis €375

ß-Glucuronidase Test for Home – Figure 1 of 3

Stuhl

β-GlucuronidaseThe enzyme that releases already-bound substances again in the gut — the opposite direction to clearance via the liver.

Eliminationgut

€45,00 Ansehen

Urin

8-OHdGThe single marker for oxidised DNA building blocks. The cheapest way in when this is the only question you have.

1 markeroxidised DNA

€60,00 Ansehen

Nitrostress - Nitrosative stress – Figure 1 of 4

Urin

NitrostressCitrulline, methylmalonic acid and nitrophenylacetic acid — the nitrogen axis from a urine sample.

Citrullinemethylmalonic acid

€100,00 Ansehen

Urin

Heavy metal measurementMetals in urine. The value shows what is being excreted — not the store in tissue. Which metals the report covers is set out in the laboratory's sample report.

Excretionsample report

€150,00 Ansehen

Urin

ZellstressprofilThe wider version: 8-OHdG on top of the nitrogen axis, plus neopterin and creatinine as a reference.

8-OHdGcitrullineneopterin

€165,00 Ansehen

Urin

Organic acidsUp to 22 markers from one urine sample, among them 8-OHdG, citrulline and methylmalonic acid alongside the rest of metabolism.

to 22 markersurine

€205,00 Ansehen

Omega-3/6 Test - Fatty Acid Analysis – Figure 1 of 3

Kapillarblut

Omega-3-IndexThe fatty acids of the cell membrane: EPA, DHA, linoleic acid, trans fats and the ratios — the structure attacked in lipid peroxidation.

EPADHAQuotienten

€90,00 Ansehen

Neurotransmitter Tryptophan Metabolism Plus – Figure 1 of 3

Urin

Tryptophan-MetabolismusNAD and the kynurenine pathway. NAD is the currency of the respiratory chain — the point where oxidative and nitrosative stress take hold.

NADKynureninIDO

€375,00 Ansehen

Kapillarblut

OM VitalThe protective side and B12 status from blood: selenium, zinc, copper, vitamin E, coenzyme Q10, homocysteine and B12.

SelenZinkQ10hs-CRP

€205,00 Ansehen

Kapillarblut

Prevent 36075 values from 120 µl of capillary blood, among them citrulline, homocysteine, coenzyme Q10, vitamin E and zinc.

75 Werte120 µl

€325,00 Ansehen

Figure 1 · Oxidative stress in the cell

Four targets in the cell, four traces in the lab

Reactive compounds do not strike at random. They attack four structures, and each leaves a different trace. For every target we say separately which marker the specialist literature names for it — and which of those we actually offer.

Cell membrane The fatty acids in the membrane are attacked and the membrane stops sealing properly. The process is called lipid peroxidation.In der Literatur: Malondialdehyde, oxidised LDLMeasurable: the omega-3 index — EPA, DHA, linoleic acid, trans fats and the ratios. That is the building material of the membrane itself.

Proteins Enzymes and transport proteins are altered and work more slowly, or stop working.In der Literatur: Carbonylated proteins, nitrotyrosineMeasurable: the amino acid profile in Prevent 360 with 18 amino acids — including tyrosine, the very amino acid nitrotyrosine forms from. Plus citrulline.

DNA The building blocks of DNA are oxidised. The damage is usually repaired; where it is not, it builds up over years.In der Literatur: 8-OHdG in urineMeasurable: 8-OHdG in urine — on its own, in the cell stress profile and in the organic acids profile.

Mitochondria The source is also the target: mitochondrial DNA sits unprotected next to the respiratory chain.In der Literatur: Reduced glutathione, ATPMeasurable: NAD in the tryptophan metabolism test and in the Longevity check-up, plus citrulline and methylmalonic acid. For glutathione itself, speak to our expert network — a medical practice can measure it.

Signal and damage The same molecules, two roles In moderate amounts, reactive compounds steer adaptation, including the formation of new mitochondria after exercise. The damage starts only when they outweigh the protective side.Reviews on redox signalling

barely reversible What peroxynitrite does to proteins The changes peroxynitrite causes in proteins are mostly not reversible and are associated with cell damage and cell death.Review on nitrative stress, ScienceDirect

Lipids, thiols, DNA How broad the targets are Peroxynitrite attacks fats, sulphur compounds, amino acids and DNA — the result is damage to membranes and mitochondria and disrupted cell signalling.Review on nitrosative stress, ScienceDirect

Figure 2 · Nitrosative stress

From arginine to nitrotyrosine

Four steps ending in a compound that alters proteins permanently. The cascade is well described — and it also shows why the markers differ so much.

Step 01 Arginine The amino acid arginine is the raw material. The enzyme NO synthase forms nitric oxide from it.

Arginine

Step 02 Nitric oxide A signalling molecule that widens blood vessels and is needed in immune defence. Useful in normal amounts.

Citrulline

Step 03 Peroxynitrite When nitric oxide meets superoxide from the mitochondria, peroxynitrite forms — the most reactive compound in this group.

Nitrophenylacetic acid

Step 04 Nitrotyrosine Peroxynitrite attaches a nitro group to the amino acid tyrosine within proteins. The specialist literature treats the product as the common marker.

Methylmalonic acid

What we measure — and what not

We do not offer nitrotyrosine itself as a self-test — a medical practice can measure it, so ask our expert network about it. Both our nitrostress profiles work from urine and measure citrulline, methylmalonic acid and nitrophenylacetic acid — substances formed on the same pathway that can be captured reliably in urine. This is not a workaround: as early as 1997 the specialist literature asked whether nitrotyrosine on its own indicates peroxynitrite at all, since it also forms by other routes. The markers we do measure are likewise non-specific and are read in context, not one by one.

Respiratory chain inhibited Nitric oxide inhibits cytochrome c oxidase reversibly. Peroxynitrite, by contrast, inhibits complexes I and III permanently.

Amino acids blocked Tyrosine and tryptophan are nitrated and are then no longer available for dopamine, serotonin and melatonin.

Membranes attacked Nitration of proteins and peroxidation of the fatty acids hit the same structure from two sides.

Mitochondria affected Mitochondria are particularly vulnerable because they are source and target at once.

3-Nitrotyrosine The marker in the literature Nitrotyrosine forms when nitrogen dioxide binds to the amino acid tyrosine within proteins. It is regarded as the main marker of nitrosative stress.Review, PMC 2020

debated since 1997 How specific is it? The question came up early: does nitrotyrosine alone indicate peroxynitrite — it also forms by other routes. Every value in this group is read in context.Halliwell B, FEBS Letters 1997

increased in diabetes Where it is studied most With raised blood sugar, peroxynitrite formation is increased; the link with secondary conditions has been described repeatedly.Pacher et al., 2007

Figure 3 · Arginine and vitamin B12

Two substances at the same point, with opposite roles

One sits at the start of the cascade, the other mops up at the end. Together they explain why nitrosative stress shows up in nutrient status.

Start of the cascade Arginin No arginine, no nitric oxide. Arginine therefore works both ways — it is the raw material for a useful signalling molecule and for the cascade that leads to peroxynitrite.

—Via nitric oxide, arginine widens the blood vessels — that is the wanted side.

—If arginine is short, NO synthase can also produce superoxide instead of nitric oxide. This is known as uncoupling.

—In cell experiments with a mitochondrial defect, L-arginine lowered nitro-oxidative stress — a cell study, not a treatment recommendation.

Measurable: citrulline — the by-product formed when nitric oxide is made from arginine. It appears in the nitrostress profile, the cell stress profile, the organic acids profile and in Prevent 360.Whether taking arginine makes sense depends on the lab report and belongs in the hands of a practitioner.

At the other end Vitamin B12 Cobalamin, the core of vitamin B12, binds nitric oxide. The vitamin itself is used up doing so — with sustained nitrosative stress the requirement rises although intake has not changed.

—B12 is a cofactor in two enzymes: the breakdown of methylmalonyl-CoA and the conversion of homocysteine back to methionine.

—If B12 is used up binding nitric oxide, both reactions run more slowly — which shows in methylmalonic acid and homocysteine.

—A low B12 status despite normal intake is therefore a lead worth following, not just a dietary matter.

Measurable: methylmalonic acid in urine — it appears in both nitrostress profiles and in the organic acids profile. Homocysteine and total B12 come from blood (OM Vital, Prevent 360). Holo-transcobalamin is not available here as a self-test; a medical practice can measure it — ask our expert network about it.With a vegan diet, after stomach surgery and while taking metformin or proton pump inhibitors, the requirement is higher anyway.

Putting it in context

Neck, cervical spine and nitrosative stress

There is a widespread idea on this topic that we come across often. We set it out and say how well it holds up.

01 Injury or misalignment in the neck What is described is whiplash, instability of the upper cervical spine, or a tilted first cervical vertebra.

02 Irritation of nerves The irritation is said to prompt the accompanying C-fibres to release inflammatory peptides — described in particular for the trigeminal nerve.

03 Nitric oxide and histamine These peptides are said to lead to the release of nitric oxide and histamine, and histamine further drives the formation of nitric oxide.

04 Nitrosative stress Nitrosative stress is said to arise from this interplay — if it persists, this concept holds that energy production in the mitochondria is disturbed.

05 Symptoms across several systems Those named include a racing heart and blood pressure swings on abrupt head movements, dizziness and exhaustion.

Where we stand

—The individual biochemical steps are described: neurogenic inflammation, release of nitric oxide, the action of histamine.

—Linking them into a disease model that explains many chronic complaints is one named author's hypothesis — not a guideline and not a consensus of the professional societies.

—We do not sell a test with the promise of proving an unstable cervical spine. That is a question for imaging and clinical examination, not for the laboratory.

—What we can measure are the markers of oxidative and nitrosative stress. What a value means is something to discuss with a practitioner.

Quellen

Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease, PMC 2020 — formation of peroxynitrite and 3-nitrotyrosine.
Nitrosative Stress — an overview, ScienceDirect Topics: reactive nitrogen species, mitochondrial damage, target structures.
Nitrative Stress — an overview, ScienceDirect Topics: irreversibility of the protein changes.
Barros CDS et al., L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency, Nutrients 2021 — cell experiment.
Halliwell B, What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo?, FEBS Letters 1997.
Reversible inhibition of cytochrome c oxidase by nitric oxide, FEBS Letters 1994.
Kuklinski B, Mitochondrien: Symptome, Diagnose und Therapie; and Substanz P, neurogene Entzündung und Xenobiotika-Suszeptibilität, Umwelt Medizin Gesellschaft 2003 — presentation of the concept.

Questions and answers

Common questions

Free initial consultation

What is the difference between oxidative and nitrosative stress?

Oxidative stress goes back to reactive oxygen species, nitrosative stress to reactive nitrogen species. They occur together and reinforce each other: nitric oxide plus superoxide gives peroxynitrite.

We measure both sides from urine — 8-OHdG for oxidised DNA, and citrulline, methylmalonic acid and nitrophenylacetic acid for the nitrogen axis. Glutathione and malondialdehyde are not available from us as self-tests — a medical practice can measure them. For the membrane side we measure the omega-3 index instead, and for the protein side the amino acid profile.

Why does vitamin B12 come up here?

Because cobalamin binds nitric oxide and is used up in the process. With sustained nitrosative stress the requirement rises, even though intake has not changed.

The marker that makes this visible is methylmalonic acid — it rises when B12 is missing in the cell, and it is in both nitrostress profiles. Homocysteine and total B12 come from blood. Holo-transcobalamin, also mentioned in the literature, is not in our range.

Should I take arginine?

There is no blanket answer. Arginine is raw material for nitric oxide and therefore also for the cascade leading to peroxynitrite. On the other hand, when arginine is short, NO synthase can additionally form superoxide.

In a cell study with a mitochondrial defect, L-arginine lowered nitro-oxidative stress. That is a laboratory result in cell cultures, not a treatment recommendation for people.

Can a misalignment in the neck trigger nitrosative stress?

There is a concept describing exactly that — put forward by the internist Bodo Kuklinski, who sees the unstable cervical spine as the main cause of chronic nitrosative stress.

The individual steps are known biochemistry; linking them into a disease model is a hypothesis, not a guideline. Neck problems, dizziness or symptoms after an accident belong with an orthopaedic and neurological assessment, not with the laboratory.

What do heavy metal values tell you?

Our test works from urine and therefore shows what is being excreted. That is different from a blood measurement, which reflects the load of recent weeks, and different again from the store in tissue.

Metals such as lead, cadmium and mercury bind to sulphur groups, and therefore to the same structures the body's own protection works through. That is why metals and oxidation markers sit together on this page. We do not carry out provocation tests with chelating agents.

Your Partner in Health

All figures come from studies and describe groups, not individual cases. Neck problems, dizziness or symptoms after an accident belong with an orthopaedic and neurological assessment, not with the laboratory.