The below paper has some insight into supplemental and genetic factors that influence height that I have not seen before.

Nutrition, Other Environmental Influences, and Genetics in the Determination of Human Stature.

“It has been proposed that human linear growth goes through phases of saltation and stasis, with short bursts of rapid growth (up to 1.65 cm within a single day) between long periods (7–62 days) of no growth at all. However, saltatory growth was not observed in human studies by other groups or in other mammals using highly precise radiological measurements. From the perspective of growth plate biology, the continuous nature of chondrocyte recruitment, proliferation, and hypertrophy is inconsistent with long periods of inactivity punctuated by acutely robust proliferation and hypertrophy. Therefore, the hypothesized model of human saltatory growth remains somewhat controversial.”<-If it is possible to grow 1.65 cm in a single day then that means that there must be a way to get around soft tissue limitations in limb lengthening surgery.

“senescence is dependent on growth itself rather than on chronological age. To put it another way, chondrocytes in the growth plate might have a finite amount of growth potential, which is gradually exhausted, leading to the decline in growth rate and associated senescent changes.”<-but that does not mean that we can not alter growth plate senescence.

“On the basis of the assumption that growth itself drives growth plate senescence, growth-suppressing conditions such as nutritional deprivation or inflammation may preserve growth potential and delay senescence”<-there may be ways to trick the growth plate to think that it needs to delay senescence even while it is still growing normally. Possible mechanisms to do this may be via SIRT1.

“Childhood stunting in the first 2 years of age is associated with reduced stature in adulthood, suggesting some permanent loss of growth potential to some degree, despite catch-up growth.”

“Endocrine factors controlling embryonic and somatotrophic fetal growth are of placental and fetal origins and include insulin-like growth factors I and II (IGF-I and IGF-II), growth hormone 2 (GH-2), and human placental lactogen (hPL). In addition, the thyroid hormones thyroxine (T4) and triiodothyronine (T3) play a central role and impact tissue accretion and differentiation as well as having an indirect role in controlling the effectiveness of other hormones including IGFs. GH-2 or placental growth hormone directly affects placental development but is also correlated with IGF-I. While IGF-II is involved in early pregnancy, in late gestation, IGF-I, synthesized in the fetal liver in response to insulin levels determined by glucose availability, controls fetal growth. hPL is secreted by the placenta and is a somatogenic hormone. Glucocorticoids can impact fetal growth, although the presence of a barrier enzyme (11-β hydroxysteroid type 2) converts maternal cortisol, which may inhibit fetal growth, to cortisone”<-what would happen if things like GH-2 and IGF-2 were upregulated in adults?

“GH excess caused by pituitary adenomas leads to elevated IGF-I and gigantism, while GH deficiency in children leads to decreased IGF-I and stunted growth. Like many other hormonal axes, IGF-I provides negative feedback to limit GH secretion in the pituitary. Therefore, children with GH receptor mutations develop a condition called GH insensitivity, where target tissues produce a muted response to circulating GH, leading to increased GH but decreased IGF-I in the circulation and poor linear growth.”<-the GH receptor may be why gigantism is so rare and HGH does not always increase height drastically. The GH receptor may adapt to excess GH.

“Because FGF21 can signal via FGFR3, it is expected to suppress bone growth in rodents via activation of FGF signaling. What is unexpected, however, is that FGF21 can also suppress bone growth in part by inducing GH resistance both in the liver and at the growth plate. A transgenic mouse model with overexpression of FGF21 showed decreased GH-induced STAT5 (signal transducer and activator of transcription 5) signaling and, consequently, diminished hepatic and local expression of IGF-I”<-reducing FGF21 levels may be a way to increase height pre skeletal maturity.

“In both humans and mice, prolonged fasting increases circulating FGF21″<-This would suggest that fasting would reduce height. It may be possible to trick the body if you block FGF21 and fast, you may boost SIRT1 levels or some other mechanism that makes the body preserve catch up growth. So you may grow normally during fasting and then get the catchup period post fasting. You could also potentially block FGFR3 via some mechanism.

“nutrient deprivation may result in decreased local IGF-I signaling at the growth plate (due to GH resistance), followed by a reduction of AKT phosphorylation and decreased recruitment of the resting zone stem cell pool into the proliferative columns. Evidently, administration of exogenous IGF-I in the system was able to restore both AKT phosphorylation and recruitment of resting chondrocytes”

“Androgen itself may have an estrogen-independent effect on stimulating bone growth, because administration of a nonaromatizable androgen in boys has been shown to accelerate linear growth. Unlike that of estrogen, this effect does not appear to be driven by an increase in the GH–IGF-I axis, but rather by a direct, local effect on chondrocyte proliferation”

“[The] effect of estrogen on bone growth is the acceleration of skeletal maturation and induction of growth plate closure. In precocious puberty, premature estrogen exposure leads to advanced bone age, premature epiphyseal fusion, and decreased adult height. Conversely, in hypogonadism, the lack of estrogen leads to delayed fusion and tall stature. Much of this effect of estrogen on skeletal maturation is mediated locally at the growth plate, by accelerating the depletion of stem cells in the resting zone”<-the reduction of estrogen to increase height pre-skeletal maturity has been studied.

“leptin has a direct effect on growth plate chondrocytes that negatively impacts catch-up growth. Refeeding after undernutrition increased leptin levels, which stimulated local aromatase activity at the growth plate and in turn accelerated estrogen-driven skeletal maturation, limiting the amount of catch-up growth. These findings provided important mechanistic insights into why undernutrition often leads to incomplete catch-up growth and permanent growth deficit.”<-So leptin may increase growth rate but result in lower final height due to enhancing estrogens negative effects,

The image above suggests that we can alter genetics somewhat via epigenetics.

“Individual nutrients have been linked to growth and described as growth promoting, such as zinc, magnesium, phosphorus, and essential amino acids. Iron deficiency, common among children and a primary cause of anemia, will result in poor growth and development, and during pregnancy it causes fetal growth restriction due to hypoxia and increased maternal stress”<-We need to know how much of these nutrients are optimal and where more would have no additional beneficial effect.

“The importance of animal source protein and essential amino acids in promoting linear growth in children”

“gut microbiota dysbiosis leads to reduced plasma amino acids”<-this may be one of the ways in which the gut microbiome influences height.

“environment-driven changes in the gut microbiota can similarly affect linear growth via this pathway, animal research suggests that microbial metabolites may also directly stimulate IGF1 gene expression”

Aripiprazole is an antipsychotic but could have beneficial effects on cartilage since the growth plate is made of cartilage this makes this medication intriguing.

Aripiprazole has been used on children for ADHD but I could not find studies on its impact on height.

Drug Repurposing: Therapeutic Role of Aripiprazole in the Cartilage Defect

“The effect of aripiprazole on cartilage was evaluated in aripiprazole-treated adipose-derived mesenchymal stem cells (ADMSCs) and chondrocyte using qRT-PCR and 3D pellet culture. The cartilage restoring efficacy was verified in vivo by mixing it with a scaffold and introducing it into the artificially damaged cartilage of Sprague-Dawley rats.
Next, mRNA was sequenced for mechanistic analysis. As a result, aripiprazole significantly increased the mRNA expression of COL2A1 and SOX9, two cartilage differentiation-related genes, and chondrogenic condensation in vitro. Moreover, it effectively promoted cartilage regeneration in the cartilage defect rat
model. Analysis of mRNA sequencing data from chondrocyte treated with aripiprazole, using KEGG and GOBP , indicated that aripiprazole significantly upregulates genes associated with ribosomes and cytoplasmic translation, thus promoting chondrogenesis. In conclusion, we discovered that aripiprazole can effectively improve damaged cartilage, providing a promising approach for cartilage regeneration.”

The question is can this be used to generation growth plates or increase articular catilage height.

“treatments with aripiprazole and irinotecan were found to elevate the expression of COL2A1, SOX9, and ACAN, genes known to promote cartilage differentiation”

“Analysis of gene expression changes in chondrocytes treated with aripiprazole revealed a significant impact on genes associated with the ribosomal pathway and translation.”

“Metformin treatment (1 mM) inhibits micro RNA-34a while promoting SIRT 1 expression in osteoarthritic chondrocytes, regulating senescence and proliferation in human chondrocytes” SIRT1 could potentially keep growth plates open for longer.

“Statin medications, such as simvastatin, have also been investigated for their potential effects on cartilage regeneration. Statins are commonly used to lower cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl-CoA. However, they also have anti-inflammatory and antioxidant properties, which may benefit cartilage repair and regeneration. This mechanism is beneficial in preventing cartilage degradation. In a
simvastatin-treated model, type II collagen loss was inhibited, and the ERK-1/2 and p38 kinase pathways regulated the simvastatin-induced differentiation of chondrocytes.”

“several repurposed drugs have been used for cartilage regeneration, including apremilast
(primarily used for psoriatic arthritis), bevacizumab (antiangiogenic drug), and suramin (medication for African sleeping sickness)”. Drugs to investigate for height increase

It seems that this medication is one to watch but more testing will have to be done to see if it can impact height. The authors primarily mention that it helps damaged cartilage which could prevent growth plate height loss and prevent articular cartilage height loss but would not give additional height.

The below paper adds to the evidence that it’s possible to increase the length of certain bones. If the mechanism by which the bones increase in length is not related to the growth plate then it is possible to increase the length of bones post puberty. Tennis involves vibration, inversion/eversion of the bone against gravity, and torsion all of which I am currently testing and have gotten slow but steady results from in length. This is not a great paper but it adds to the evidence that loading in the right manner can increase bone length. It is cited in Susan Pfeiffers paper who showed that it is possible to increase arm bone length post skeletal maturity.

Unilateral Activity and Bone and Muscle Development in the Forearm

“Tennis players exercise one arm almost exclusively and mere inspection shows that they develop one arm more than the other. A comparison was made of the arms of tennis players to evaluate alterations in muscular development and bony structure associated with extensive unilateral activity. In order to assess whether differences between arms of tennis players were larger than for normal young males (non-tennis players), a group of soldiers was also studied.”

“seven nationally ranked tennis players from the Minnesota-Wisconsin-Iowa area and 11 soldiers from Fort Lee, Virginia, were used as test subjects”

“All of the tennis players had played tennis regularly winter and summer for at least the last seven years. None of the soldiers had engaged in any type of extensive unilateral activity.”
“Hand area, third-finger length, wrist width and the forearm circumference measurements differed between the arms of the tennis players but not between the arms of the soldiers.”

“Ulna length proved to be significantly different in both groups, but a slightly more significant difference was noted between arms of tennis players than soldiers. Radius length differed only in tennis players”

You can see that the tennis players had greater length asymmetry than the soldiers. The third finger length asymmetry was pretty much the same which is interesting.

“Contralateral arm movement is necessary to elevate the ball for the service as well as to steady the racket prior to hitting the ball during the volley and when hitting ground strokes.”<-So rapid inversion/eversion of the arm. Torsional loading to grip the racket. And vibration when the ball hits the racket.

“Bony lengths were increased in the dominant forearm of tennis players, indicating an alteration in the osseous “growth apparatus””

“Hand area, hand width, third-finger length, wrist width, and forearm circumference (relaxed and contracted) differed significantly between the dominant and other arm of tennis players, but only hand width, wrist width and forearm circumference (contracted) differed between arms of soldiers.
Radius and ulna length and distal ulna width were different between the arms of tennis players but only ulna length differed between arms of soldiers.”

“small changes in radius and ulna length could be associated with participation in this vigorous unilateral activity.”

It should be noted that soldiers also engage in unilateral activities with their dominant arm. So it is likely that the types of loads that occur in tennis are the kinds of loads that induce growth in length and we should attempt to apply those loads to the legs.

There is evidence that the gut microbiome influences height via IGF-1. Microbiomes are passed on from mothers to children so it is non genetic way to influence height. Here’s more information about how the guy microbiome influences height.

The gut microbiome is definitely something that has a lot of effort put into it by the scientific community so there is potential to optimize the gut microbiome to make people taller.

Island biogeography theory provides a plausible explanation for why larger vertebrates and taller humans have more diverse gut microbiome

“Prior work has shown a positive scaling relationship between vertebrate body size, human height, and gut microbiome alpha diversity.{this means that the more diverse your gut microbiome the taller you were. This could be a correlation rather than causal if there is a factor that increases human height and gut microbiome diversity}.
This observation mirrors commonly observed species area relationships (SARs) in many other ecosystems. Here, we expand these observations to several large datasets, showing that this size–diversity scaling relationship is independent of relevant covariates, like diet, body mass index, age, sex, bowel movement frequency, antibiotic usage, and cardiometabolic health markers. Island biogeography theory (IBT), which predicts that larger islands tend to harbor greater species diversity through neutral demographic processes, provides a simple mechanism for positive SARs. Using a gut-adapted IBT model, we demonstrated that increasing the length of a flow through ecosystem led to increased species diversity, closely matching our empirical observations. We delve into the possible clinical implications of these SARs in the American Gut cohort. Consistent with prior observations that lower alpha diversity is a risk factor for Clostridioides difficile infection (CDI), we found that individuals who reported a history of CDI were shorter than those who did not and that this relationship was mediated by alpha diversity.{so increased microbiome diversity reduces the risk of infection}.

We observed that vegetable consumption had a much stronger association with CDI history, which was also partially mediated by alpha diversity. In summary, we find that the positive scaling observed between body size and gut alpha diversity can be plausibly explained by a gut-adapted IBT model, may be related to CDI risk, and vegetable intake appears to independently mitigate this risk, although additional work is needed to validate the potential disease risk implications.”

So this indicates that vegetable intake is a good way to increase microbiome diversity.

“The human gut microbiota has an enormous impact on our phenotype, with almost half of the metabolites circulating in blood significantly associated with cross-sectional variation in the ecological composition of the gut microbiome. One of the key ecosystem functions that the gut microbiota provides to its host is resistance to enteric bacterial pathogens. Niche saturation or nutrient competition are commonly invoked mechanisms for how the microbiota excludes invaders.”

“species-diverse commensal communities are more apt to saturate available metabolic niches
so that an invasive pathogen is less likely to colonize, outcompete commensals, and cause disease”<- so one of the ways that the gut microbiome increases height is by competing with invading pathogens and thereby preventing them from stunting growth. However if it is due to preventing infection that height is increased it could mean that for the average person the microbiome has less impact on height if they would not get an infection otherwise. On the other hand, the microbiome has been shown to have other effects that influence height such as via IGF-1.

“Vertebrate body size, which varies over six orders of magnitude, has been shown to be positively associated with gut microbiome alpha diversity, indicating that larger animals with larger guts harbor more species.” <-so the correlation could be possibly caused by larger people having larger guts which enable more microbiome diversity.

“we demonstrate a consistent scaling between body size and gut microbiome alpha diversity across vertebrates and human populations. We find that this association is independent of many potential confounders, like diet, bowel movement frequency (BMF), body mass index (BMI), age, and sex”

What the next steps would be to test the influence of the microbiome would be to compare the growth rates of different animals versus microbiome diversity who have never had an infection.

But with the frequency that kids get sick even if microbiome only reduces infection risk then it is worth it.

This paper has interesting insights on how mechanical loading and gravity can enhance longitudinal bone growth.

Intermittent mechanical loading on mouse tibia accelerates longitudinal bone growth by inducing PTHrP expression in the female tibial growth plate

“Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4-week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones.”

This suggests that possibly boosting PTHrP directly could induce additional longitudinal bone growth.

“Mechanical forces related to gravitational changes, ambulation, and exercise may contribute to modulate bone growth.”<-this suggests that exercises that invert and every may modulate longitudinal bone growth.

“daily physical activities transmit complex mechanical loads including tension, compression, torsion, and shear to the skeleton”<-there are many ways to load bones that are under explored.

“Seventy-five 4-week old TOPGAL mice were exposed to mechanical loading using a Bose ElectroForce 3220 dynamic loading system. Before each loading session, mice were anesthetized with 3.5% isoflurane. Each loading session included 100 compressive loading cycles of 5 Newton (N) force to the right tibia at the frequency of 2 Hz per cycle”<-the reason that cyclic loading is more effective than static loading is likely related to fluid flow.

“mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae, in the whole sample of mice “

“Gravity and physical activity generate mechanical forces on the long bones and on the growth plates that may be involved in the regulation of bone growth.”<-one of the reasons why lateral loads are so effective is that it applies loads in a different mannerism against gravity.

“Of note, the stimulatory effect of mechanical loading on tibial growth persisted in the 4 weeks following the cessation of loading.

In addition, at the end of the 4-week loading period the whole growth plate and the epiphyseal zone heights, as well as the overall area of the loaded tibial growth plates were significantly greater than those of the unloaded growth plates. Such finding suggests a loading-mediated enhanced growth plate chondrocyte formation”

The study mentions that too high load can suppress growth. So maybe lighter weights are better and applying it the right way is more important but that may be for growth plates and not bones. Higher loads may be needed to stimulate growth in adult bones as bones are tougher tissue than catilage.

“similar studies in rodents indicate that elevated loading forces tend to inhibit longitudinal growth, while strains of lower intensity (like ours) tend to stimulate it. “

“After 4 weeks of loading, we found a greater Pthrp gene expression in the growth plate chondrocytes of the female mouse loaded tibiae, while no difference was found in male mice” however male mice also had greater length. So this suggests that mechanical loading also influences length by mechanisms not related to PTHrP.