Thursday, July 5, 2012

Does coffee stunt growth?

That coffee stunts growth has long been a rumor circulated amongst individuals wishing to grow taller.  Is it true?

Adrenocorticotropin evokes transient elevations in intracellular free calcium ([Ca2+]i) and increases basal [Ca2+]i in resting chondrocytes through a phospholipase C-dependent mechanism.

"The melanocortin peptide, ACTH, [is involved] in the terminal differentiation of chondrocytes. Terminal differentiation along the endochondral pathway is responsible for linear growth. Chondrocyte terminal differentiation is associated with an incremental increase in chondrocyte basal intracellular free calcium ([Ca(2+)](i)), and ACTH agonism of melanocortin receptors is known to mobilize [Ca(2+)](i.){We know that intracellular calcium secretions play an important role in chondrocyte differentiation} Using differentiated resting chondrocytes highly expressing type II collagen and aggrecan, we examined the influence of both ACTH and dexamethasone treatment on matrix gene transcription and [Ca(2+)](i). Resting chondrocytes treated concurrently with dexamethasone and ACTH expressed matrix gene transcripts in a pattern consistent with that of rapid terminal differentiation. Using the fluorescent Ca(2+) indicator, fura-2, we determined that ACTH evokes transient increases in [Ca(2+)](i) and elevates basal Ca(2+) levels in resting chondrocytes. The transient increases were initiated intracellularly, were abrogated by the phospholipase C-specific inhibitor, U73122, and were partly attenuated by myo-inositol 1,4,5-triphosphate receptor inhibition via 10 mm caffeine{so caffeine inhibits the transient increases in calcium}. The initial intracellular release also resulted in store-operated calcium entry, presumably through store-operated channels. Dexamethasone priming increased both the initial ACTH-evoked [Ca(2+)](i) release and the subsequent store-operated calcium entry. These data demonstrate roles for ACTH and glucocorticoid in the regulation of chondrocyte terminal differentiation. Because the actions of ACTH are mediated through known G protein-coupled receptors, the melanocortin receptors, these data may provide a new therapeutic target in the treatment of growth deficiencies and cartilage degeneration."

So it's possible that caffeine reduces transient secretions in calcium thus inhibiting chondrocyte differentiation and thereby reducing growth.

"Caffeine at high concentrations (10–20 mM) will inhibit IP3 receptor activation. RC cultures were treated with 10 mM caffeine or vehicle for 100 sec before the addition of 10−7 M ACTH. Caffeine greatly reduced ACTH-induced Ca2+ release, suggesting that at least a portion of the Ca2+ released is via IP3 binding to its receptor. Additionally, caffeine is a known agonist[activator] of the ryanodine receptor. Stimulation of this receptor by caffeine and/or ryanodine will also elicit Ca2+ release. Because caffeine itself does not elicit transient elevations in [Ca2+]i, it is unlikely that [resting chondrocytes] in this differentiation state are expressing ryanodine receptors, and therefore it is unlikely that ACTH evokes Ca2+ release through this mechanism."

So caffeine activates other kinds of calcium release-related receptors even though it blocks ACTH Ca2+ release.  However, we're looking for what activates calcium release in mesenchymal stem cells and resting chondrocytes are close to MSCs.  Therefore, it is possible that coffee does not compensate for it's growth stunting of ACTH through the ryanodine receptor.

Here's a study that studies caffeine directly on endochondral bone development in rats:

Inhibition of induced endochondral bone development in caffeine-treated rats.

"In fetal rats, delayed ossification [is] induced by caffeine at maternal doses above 80 mg/kg body weight per day. Caffeine's effects on cellular events associated with endochondral ossification were examined directly by quantitating cellular mRNA levels of chondrocyte and osteoblast growth and differentiation markers in DBP[demineralized bone particles] implants from caffeine-treated rats harvested at specific stages of development (day 7 through day 15). Oral caffeine administration to rats implanted with DBP resulted in a dose dependent inhibition of the formation of cartilage tissue in the implants. Histologic examination of the implants revealed a decrease in the number of cells which were transformed to chondrocytes compared to control implants. Those cartilaginous areas that did form, however, proceeded through the normal sequelae of calcified cartilage and bone formation. At the 100 mg/kg dose, cellular levels of mRNA for histone, collagen type II, and TGF beta were all reduced by greater than 40% of control implants consistent with the histological findings. Alkaline phosphatase activity in the implants and mRNA levels for proteins reflecting the hypertrophic chondrocyte and bone phenotype, collagen type I and osteocalcin were markedly decreased compared to controls. Lower doses of 50 and 12.5 mg/kg caffeine also resulted in decreased cellular proliferation and transformation to cartilage histologically and reflected by significant inhibition of type II collagen mRNA levels (day 7). The effects of caffeine on gene expression observed in vivo during the period of bone formation (day 11 to day 15) in the DBP model were similar to the inhibited expression of H4, alkaline phosphatase, osteocalcin, and osteopontin found in fetal rat calvarial derived osteoblast cultures following 24 hour exposure of the cultures to 0.4 mM caffeine. Thus the observed delayed mineralization in the fetal skeleton associated with caffeine appears to be related to an inhibition of endochondral bone formation at the early stages of proliferation of undifferentiated mesenchymal cells to cartilage specific cells as well as at later stages of bone formation."

Now it's possibly that caffeine only delays growth and individuals who use caffeine just grow slower. I believe this has been the observation with Ritalin.

Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation.

"Maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Pregnant Wistar rats were injected intragastrically with 120mg/kg of caffeine intragastrically each day from gestational day 11 to 20. Maternal prenatal caffeine exposure was associated with decreased fetal femur lengths and inhibited of synthesis of extracellular matrices in fetal growth plates. Moreover, caffeine exposure significantly increased the levels of fetal blood corticosterone and decreased IGF-1mRNA expression levels in the liver and growth plate. The expression levels of IGF-1 signaling pathway components (IGF-1R, IRS-1{down in LSJL}, AKT1/2{LSJL increases Akt phosphorylation} and Col2A1{up in LSJL}) were also reduced. Caffeine exposure down-regulated histone methylation of fetal IGF-1 in the liver. These results suggest that prenatal caffeine exposure may inhibit fetal skeletal growth through a mechanism that is associated with increased fetal exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway activity. [Caffeine may be toxic to] skeletal growth."

"Caffeine is a xanthine alkaloid"

"[Other studies report that] caffeine intake during pregnancy is not associated with changes in birth weight or length"

"caffeine elevates GC levels in adult humans and animals"

"caffeine exposure results in reduced expression levels of chondrogenesis-specific genes, including Col1A1, Col2A1, and aggrecan"

Although, it 's likely that this may only affect growth rate and not adult height.

At minimum caffeine delays growth by inhibiting calcium secretions which allow for chondrogenic differentiation.  Since the goal of LSJL is to induce chondrogenic differentiation, caffeine should not be consumed around the performance of LSJL.  Reports have stated that caffeine can remain in the system for 5 to 9 hours.  It's possible that LSJL can still function even with caffeine in the body but it'll make it harder for LSJL to generate fluid shear on bone marrow MSCs to generate calcium secretions to induce chondrogenic differentiation.

To my knowledge there are no longitudinal studies on caffeine and catch-up growth so we can see if the proliferative capacity is conserved or if caffeine does in fact stunt growth.


  1. Caffeine affects estrogen levels. Estrogen has a huge impact on growth plate ossification. This is one reason why caffeine could potentially stunt growth.

  2. Most people get their caffeine through sources other than coffee such as tea, sodas, energy drinks, etc...

    The title should read "Does Caffeine Stunt Growth?"

    A lot of people don't drink coffee and, glancing at the title, don't read the article thinking it doesn't apply to them.