Collagen in your head: where it is, and where it isn't
When you think of collagen, you probably think of skin, tendons and bone. Fair enough: collagens are the most abundant proteins in mammals¹. And there isn't just one collagen but a family of 28 types¹. What about the brain? This is where it gets surprising: in the nervous system, collagens are rare near the cell bodies of nerve cells².
That runs against a popular picture – collagen as the scaffold that holds the nerve cells in your brain together. It isn't that simple. The next sections show where collagen really occurs in and around the brain, what research knows about it and what is still an open question.
On the edges: meninges, blood vessels and early development
Where the collagens are
Rather than between the nerve cells, collagen is found mostly at the edges: in the meninges, in basement membranes and in the sensory end organs². Basement membranes are wafer-thin sheets of matrix that cells sit on.
The brain's matrix – everything between and around its cells – falls roughly into two parts: connective tissue in the form of basement membranes along the meninges and blood vessels, and a matrix inside the nerve tissue itself³. The latter consists of loose material between the cells and of so-called perineuronal nets³. In some nerve cells, these nets wrap around the cell body and the dendrites⁴. They are made mainly of hyaluronan, chondroitin sulfate proteoglycans, link proteins and tenascin R⁴ – collagen is not on that list.
Collagen as a signpost during development
Development is where it gets interesting. Here, recent studies indicate that collagens are involved when nerve fibres find their way, when synapses form and when Schwann cells mature². For a long time, research largely overlooked this role in wiring up the nervous system⁵. Only more recent studies unexpectedly uncovered such roles for collagens in the developing nervous system⁵. This concerns the construction phase of the nervous system.
The blood–brain barrier: home of collagen IV
The brain shields itself from the blood with the blood–brain barrier. It is made up mainly of the cells lining the vessel wall (endothelial cells), pericytes, astrocytes and a basement membrane⁶. The cells get most of the attention; the basement membrane, the only non-cellular part, is largely understudied⁶.
A layer 50 to 100 nanometres thick
The basement membrane is a highly organised sheet of protein just 50 to 100 nanometres thick⁶. It consists essentially of four proteins: collagen IV, laminin, nidogen and perlecan⁶. Collagen IV is the most abundant of them⁶. Its network is thought to form the scaffold into which the other components, such as laminins, nidogens or perlecan, are fitted⁷.
What happens when collagen IV is missing
Experiments in mice show some of what collagen IV does: when mouse embryos lack the main form of collagen IV entirely, their basement membranes still form at first⁷. But once mechanical demands increase, they no longer hold: the embryos die at around day 10.5 to 11.5 of embryonic development⁷. Mice with a specific change in the collagen IV gene on just one of their two gene copies show damage to their brain vessels, including bleeding in the brain⁶. The authors of a review conclude that collagen IV plays a crucial role in keeping vessels intact⁶.
To put this in context: these are faults in the blueprint, in the genes. They have nothing to do with how much collagen is in your diet. And exactly how the basement membrane regulates the barrier at the molecular level is still largely unknown⁶.
Nerves and myelin: the collagen sits outside the brain
For signals to travel fast along long nerve fibres, many fibres are wrapped in myelin, a fatty insulating layer. In the brain and spinal cord, this myelin is made by oligodendrocytes; in the nerves of the rest of the body, by Schwann cells³. When it comes to collagen, that difference is decisive.
In the body's nerves: Schwann cells in a collagen sleeve
In the peripheral nervous system, Schwann cells are surrounded by a basement membrane⁸. Two classes of collagen occur there: the fibre-forming collagens of types I, III and V, and the basement-membrane collagen type IV⁹. Collagens are key components of peripheral nerves: they don't just provide structural support, they also influence how cells behave by triggering signals⁸. Collagen VI is one example: it regulates how Schwann cells mature and is needed to preserve the myelin of peripheral nerves³.
In the brain: an open question
The brain is a different story. While the role and distribution of collagen VI in peripheral nerves are well established, its role in the central nervous system remains an open field of research³. Collagen VI is also known to be far more abundant in peripheral nerves than in the brain and spinal cord³.
More collagen isn't automatically better
A detail from nerve repair shows how fine the balance is: after an injury, the severed nerve often makes more collagen than would be ideal⁹. This scarring is thought to stop regrowing nerve fibres from finding their way, and so to delay regeneration⁹.
Collagen and ageing: what has been measured, and what hasn't
"The body loses collagen as it ages" – for skin there are measurements, though of how much is made: aged skin makes less collagen of types I and III¹⁰. In the lab, skin cells (fibroblasts) from people over 80 produced less of the precursor of type I collagen than those from 18- to 29-year-olds¹⁰.
This finding can't simply be carried over to the brain. There, collagens are rare near the nerve cells², and in the basement membranes of its vessels the most abundant component is collagen IV⁶ – not the skin collagens I and III. In mice, the genes for collagen VI actually became more active with age³ – not a sign of loss.
In brain diseases, the make-up of the basement membrane around the vessels changes considerably¹¹. Whether such changes are a cause or a consequence, that observation alone can't tell. No measurement showing that the human brain loses collagen with age appears in the papers reviewed here.
Collagen from food: what reaches the blood
Your body builds its collagen itself, from amino acids. For that it needs enzymes and their helpers: vitamin C is required to convert the amino acid proline in collagen precursors into hydroxyproline, and hydroxyproline stabilises collagen's triple helix¹². The enzyme lysyl oxidase, which cross-links collagen fibres, needs copper¹³.
Peptides in the blood
So what happens to collagen you eat? In a study of ten healthy men, blood levels of nearly all amino acids rose over 240 minutes after 35 g of collagen hydrolysate¹⁴. Not everything is broken down into single amino acids: after gelatin hydrolysate (9.4 to 23 g), the peptide form of hydroxyproline rose in the blood of healthy volunteers and peaked after one to two hours¹⁵. The main component of these food-derived peptides was the dipeptide prolyl-hydroxyproline (Pro-Hyp)¹⁵.
Broth or powder?
Bone broth is often seen as a natural source of collagen. One analysis, however, found that broth made to a standard recipe contained significantly less hydroxyproline, glycine and proline than a 20 g serving of the collagen supplements used in research¹⁶. In freely prepared broths, the amino acid content varied widely¹⁶.
What remains open
All of these studies measured blood, not the brain. Whether collagen peptides from food change the collagen in or around the brain is not something they answer.
In short: less foundation, more fine detail
The brain is not held together by a collagen scaffold: near the nerve cells, collagen is rare². It sits mostly at the edges, in the meninges and in basement membranes². In the basement membrane of the blood vessels, collagen IV is the most abundant component⁶. During development, studies indicate that collagens are involved when nerve fibres find their way². In the nerves outside the brain and spinal cord, they are among the key building blocks⁸.
As for collagen from food, the picture is sober: peptides such as Pro-Hyp can be detected in the blood¹⁵. Whether they change anything in the brain was not examined in the papers this article draws on. Anyone who promises you otherwise should be able to name the study.