Cruciferous vegetables & sulforaphane

Every food in this section runs into the same question at the same point: does any of it get to the joint? For broccoli, that question has an answer, and the answer was obtained the direct way — by taking fluid out of the knees of people who had been eating it.

Sulforaphane is not in broccoli

Broccoli contains glucoraphanin, a glucosinolate, and it separately contains myrosinase, the enzyme that converts glucoraphanin to sulforaphane. The two are held apart in the intact plant and meet when the cell walls are broken — which is to say, when you chew. Stomach acid then inactivates myrosinase irreversibly, so conversion that does not happen in the mouth does not happen later.

That makes preparation the dose. In a simulated digestion, raw and one-minute steamed broccoli yielded up to ten times more sulforaphane than broccoli steamed longer; adding protein or fat to the meal made no difference at all. It is the same lesson as the collagen entries in this section, arriving from the opposite direction — there, long cooking is what makes the food work; here, it is what stops it.

The two rows worth pausing on are myrosinase and sulforaphane nitrile. The enzyme is the whole conversion step and it is fragile; and the same precursor can break down into a compound nobody has tested, depending on conditions nobody controls in a kitchen.

What it does to cartilage

Sulforaphane suppressed cytokine-induced metalloproteinase expression in primary human articular chondrocytes and in synovial cells, and at 10 μM it abolished cytokine-driven destruction of cartilage explants — at both the proteoglycan and the collagen level, which are usually separable. In mice with destabilized menisci, a sulforaphane-rich diet supplying 3 μmol a day lowered the arthritis score and blocked the early gene-expression changes that precede damage.

The mechanism is contested in an interesting way. That study found the effect ran through NF-κB inhibition and prolonged JNK and p38 activation and was independent of Nrf2 — the antioxidant pathway sulforaphane is famous for. Other groups place it on Nrf2, and another on SIRT1. Chondrocyte protection has been replicated by a group with no connection to the original programme, across several different death stimuli.

In STR/Ort mice, which develop osteoarthritis spontaneously rather than after surgery, stabilized sulforaphane reduced gait abnormalities and changed subchondral bone architecture — useful because no joint was cut to start the disease.

Isothiocyanates in the synovial fluid

Forty patients with knee osteoarthritis, all awaiting total knee replacement, were randomized to a high- or low-glucosinolate diet for the fourteen days before their operation. Isothiocyanates were present in the synovial fluid of the high-glucosinolate group and absent in the low group, with plasma isothiocyanates and sulforaphane following the same pattern. Proteomic analysis of the synovial fluid separated the groups on 125 differentially expressed proteins.

That is the delivery question answered in the target tissue, which no other food in this section can claim. It is also, precisely, not an efficacy result: the trial measured what arrived, not what improved, and its authors describe it as proof-of-principle with the functional trial to follow. The broccoli used was a patented high-glucoraphanin variety, with a named inventor among the authors and the patent licensed to a seed company — disclosed in the paper.

How much any given person gets

Two studies say the dose is not a property of the vegetable alone. In a crossover trial in 18 adults, exposure to isothiocyanate metabolites from identical broccoli diverged by body mass index: above a BMI of 26, eating broccoli daily produced lower plasma exposure than not eating it habitually; below 26, higher. GSTM1 genotype, the usual suspect, did not explain it. And adding active myrosinase to a preparation raises the yield, while a proton pump inhibitor changes how much is absorbed.

The practical version of all that is unglamorous: chew properly, cook briefly, and note that adding a raw myrosinase source — radish, mustard — is the standard way to restore conversion in brassica that has been cooked through.

The findings that point the other way

Sulforaphane arrests rabbit chondrocyte proliferation at G2/M. The cell-cycle effects that make it interesting in cancer research are not obviously wanted in a tissue with few cells and almost no turnover. In synoviocytes it does opposite things depending on their state — activating protective Nrf2 signalling in resting cells and inducing apoptosis in TNF-α-stimulated ones — and in that study it did not significantly reduce MMP-3 or MMP-9.

And when investigators wanted a reliable sulforaphane concentration in a joint, they did not feed it: they built slow-release microspheres and injected them.

Against the cohort evidence — higher vegetable intake associated with fewer femoral head cartilage defects (OR 0.65, 95% CI 0.46–0.91) and fewer bone marrow lesions (OR 0.60, 95% CI 0.37–0.97) in 214 adults with hip MRI — sits a Mendelian randomization of eighteen dietary factors against knee OA in which neither cooked vegetables nor salad reached significance. Those measure different things, and both belong on the page.

What would change this entry

The functional trial the 2017 paper said was coming. This is the most tractable missing study in the foods section, because the hard half is already done: the compound has been shown to reach the tissue, in the disease, in people. What remains is to find out whether it matters there.