Tart cherry juice

Tart cherry is the folk remedy that got tested. It has been drunk for gout for long enough that the pharmacology arrived afterwards, and unusually for this section, the pharmacology held up: the compound responsible is identified, its target in cartilage is identified, and the gap between the cell work and the kitchen is measurable rather than assumed.

What cyanidin does to a chondrocyte

Anthocyanins are the pigments; in Montmorency cherries the dominant ones are cyanidin 3-glucosylrutinoside and cyanidin 3-rutinoside. In human osteoarthritic chondrocytes stimulated with IL-1β, cyanidin suppressed nitric oxide, PGE2, TNF-α, IL-6, iNOS and COX-2, and — the part that matters for cartilage rather than for inflammation generally — suppressed ADAMTS5 and MMP13, the two enzymes that cut aggrecan and type II collagen, with less loss of both matrix proteins as a result. Silencing Sirt6 abolished the effect, which places the mechanism on a specific axis rather than leaving it as generic antioxidant activity. In mice with surgically destabilized menisci, cyanidin slowed the progression of OA.

Anthocyanins as a class do something adjacent that connects this entry to another: in human cartilage explants exposed to advanced glycation end-products, they reduced the glycosaminoglycan and uronic acid bleeding out of the matrix. The same class of experiment cuts the other way too — in stem cells differentiating toward cartilage, cyanidin suppressed the hypertrophic markers Runx2 and Col10a1, but suppressed the chondrogenic markers Sox9 and Col2a1 along with them.

The knee trial

Fifty-eight adults with Kellgren-Lawrence grade 2-3 knee osteoarthritis drank two 8 oz bottles of tart cherry juice or a matched placebo daily for six weeks, crossed over with a one-week washout, analysed by intention to treat. WOMAC scores fell significantly during the cherry period (p < 0.01) and did not fall during the placebo period (p = 0.46). The between-treatment difference — the comparison the design exists to make — came in at p = 0.16.

The biomarker went the other way. hsCRP fell on cherry juice relative to placebo (p < 0.01), and the size of each person's hsCRP fall tracked the size of their WOMAC improvement (p < 0.01). Walking time, rescue acetaminophen, plasma urate and creatinine were unaffected. That combination — a between-group biomarker separation, a within-group symptom change, and a correlation linking them — is a reason to run the trial again at a size that can settle it, and it is the specific thing that would move this entry.

The gout literature, and why it sits outside the tier

Most of what has been measured about cherries in humans concerns urate and gout attacks. In 633 people with gout followed for a year, cherry intake in the two days before an attack was associated with 35% lower attack risk (OR 0.65, 95% CI 0.50–0.85); with allopurinol on top, risk was 75% lower than with neither (OR 0.25, 95% CI 0.15–0.42). A crossover trial in 26 overweight adults lowered serum urate by 19.2%, and a 2026 meta-analysis of four trials in 392 people pooled to a standardized mean difference of −0.22 (95% CI −0.43 to −0.01).

Against that, a dose-ranging randomized trial in 50 people with gout — run in part by two authors of the case-crossover study, testing their own hypothesis — found no effect of any dose from 7.5 to 30 mL twice daily on serum urate, urine urate excretion, urinary anthocyanin, or flare frequency. Their conclusion is worth keeping: if cherry concentrate does reduce flares, urate lowering is not the route. And in 282 men starting febuxostat, a tart-cherry citrate mixture matched plain citrate and sodium bicarbonate on both co-primary endpoints, beating them only on CRP and albuminuria — with the cherry bundled inside the citrate, so the trial cannot say which ingredient did it.

Gout is crystal arthritis. It shares a joint with osteoarthritis and almost nothing else, so this literature informs the entry without setting its tier.

How much of it gets into you

The step most cherry research skips has been measured. After drinking the juice, cherry anthocyanins do appear in plasma — at very low concentrations, cleared quickly, and mostly as metabolites rather than the parent compounds used in the cell experiments. That gap between the concentration that silences MMP13 in a dish and the concentration a drinker reaches is the honest reason the mouse result has not translated yet, and it applies to every polyphenol entry in this section.

Thirty days of Montmorency cherry, as concentrate or freeze-dried, moved nothing in 58 healthy adults — not CRP, not ESR, not uric acid, not the gut microbiome. Healthy people with normal markers are a hard population to improve, so that null says less than it looks like, but it is the largest supplementation study in the topic.

Practical notes

The knee trial used roughly 480 mL of juice a day; the urate work uses 240 mL, or 7.5–30 mL of concentrate twice daily. That is a meaningful sugar load, which is worth weighing against what the cohorts say about sweetened drinks. Concentrate delivers an anthocyanin dose nobody reaches by eating fruit, and two published case reports describe acute kidney injury on black cherry concentrate in people who already had chronic kidney disease — attributed to COX inhibition by anthocyanins, the same mechanism the benefit rests on.

What would change this entry

A parallel-group knee-OA trial powered on hsCRP and WOMAC together. The existing trial produced a between-group biomarker effect that correlated with symptoms in the same people; that is a specific, testable lead rather than a general hope, and it is unusual for a food to have one. A registered trial of tart cherry juice against gout attack frequency is also underway, which would settle the older half of the story.