Frequently Asked Questions

If you flip through the page corners from back to front, you'll see a flip-book-style cartoon illustrating the chain reaction of lipid peroxidation, with grey penguins representing D-PUFAs. Additional guidance on page 69 and page 265. This animation only works in the printed edition.

An isotope is a variant of a chemical element with the same number of protons but a different number of neutrons. Deuterium, for example, is a stable isotope of hydrogen: it has one proton and one neutron instead of just a proton. This subtle difference makes deuterium-carbon bonds harder to break, which is why D-PUFAs resist lipid peroxidation.

Peroxidation is the oxidation of lipids (fatty molecules) by reactive oxygen species, producing peroxides and other harmful by-products. In biology, lipid peroxidation is the most consequential form—it damages cell membranes and drives aging and age-related diseases.

Chemical isotopes have the same number of protons (and thus the same chemical identity) but different masses due to different numbers of neutrons. Heavier isotopes form slightly stronger bonds that are harder to break. Deuterium, the heavy isotope of hydrogen, slows down reactions that involve breaking C-H bonds—including the chain reaction of lipid peroxidation in cell membranes.

Aging is multifaceted and to slow it down will require a coordinated use of various interventions. That said, LPO stands out as a major contributor, largely due to the utter importance of lipid membranes to biology. 30% of all biochemical reactions happen in membranes. Neurons, mitochondria, the visual apparatus and many other things rely on membrane integrity for their function. And all that can be compromised, or destroyed, by LPO, pushing aging forward.

It increasingly looks so. Consider traumatic brain injury: the initial concussion produces a burst of lipid peroxidation, can years later yield Parkinson's, Alzheimer's, various dementias, ALS, MS or other ailments, indeed implicating LPO as a unifying mechanism behind these conditions.

People usually think about reduced membrane fluidity and impaired barrier function. This, however, pales in comparison with the downstream consequences. Oxidised fatty acids fragment into smaller pieces, which are often highly reactive. These can wreak havoc by reacting with one, or several, biomolecules, leading to accumulation of large insoluble waste deposits.

Both. Transition metals are genuinely Janus-faced. Enzymes need small amounts of them as essential cofactors, yet the very properties that make them useful inside enzymes make them hazardous when they're free in the cell. In particular, transition metals can generate reactive oxygen species (ROS), which in turn can trigger the radical chain reaction of lipid peroxidation.

They are incomparable. Antioxidants are tightly controlled and their levels in membranes cannot exceed certain fixed values, at best. At worst, they can do an about-face, turning into pro-oxidants. As smokers on antioxidants learned, at their peril, in a human clinical trial.

No. Suppose you have a wooden (= PUFA) fence. You'll need to keep stomping out (= antioxidant) fires (= ROS) approaching it to preserve it. Now suppose the fence is the same shape and size, but made of concrete… Antioxidants are used up stopping the fire, while D-PUFAs are just impervious.

No. Deuterium is a stable isotope of hydrogen.

No. Our bodies are well adapted to its natural presence (150 ppm, or 0.015% in sea water). Roughly, every 6500th atom of hydrogen is deuterium, giving 33 g deuterium per cubic metre of sea water. A typical human body contains about 1.5 g of deuterium, distributed across body water and organic molecules.

Given its low abundance, it takes a lot of effort to separate (concentrate) heavy water from fresh water. While various methods exist, they are all energy-hungry.

Affecting the chain at every step, the kinetic isotope effect "accumulates" along the entire chain, producing values far higher than those seen in the single-step reactions.

Yes. D-PUFAs travel through the body exactly as normal PUFAs do. As essential nutrients, PUFAs (and D-PUFAs) are absorbed in the small intestine, repackaged by liver and carried through the bloodstream to tissues throughout the body, first and foremost to those that need them most.

Through multiple interconnected mechanisms. Oxidized lipids are inherently pro-inflammatory, for example in the atherosclerosis setting. Some end-products of LPO, such as isoprostanes, mimic the structure of pro-inflammatory prostaglandins, so keeping them at low levels is beneficial. Other LPO end-products can irreversibly glue various biomolecules together, generating persistent inflammatory background. Lipoxygenases and cyclooxygenases convert arachidonic acid into a smorgasbord of predominantly pro-inflammatory eicosanoids. With age, these processes pile up, collectively contributing to "inflammaging". This pro-inflammatory "noise" can be mitigated by D-PUFAs.

No. Aspirin covalently reacts with COX enzymes, irreversibly "killing" them. Inhibitors of COX and LOS are enzyme-specific, and as a result often skew the important fine balance of various eicosanoids, such as in aspirin-sensitive asthma. D-PUFAs act across the board, softly down-regulating all COX and LOX enzymes. This dials down without distorting the delicate ratios.