Psyllium

Psyllium is the common name for products derived from the plant Plantago ovata^[2] which the synonym of Plantago psyllium^[3] or ispaghula;^[4] and is more commonly known as the brand name Metamucil. Psyllium currently as a generally recognized as safe (GRAS) status in the US, and is commonly used in clinical settings for the purpose of bulk laxation (laxative effects secondary to fecal forming properties); a distinct laxative effect from more commonly used defecation-inducing compounds such as Senna Alexandrina or Polyethylene glycol (PEG), psyllium is known to be 'gentler' of a laxative and to facilitate passing of softer and sleeker stool.^[5][6][7] Traditional usage of Plantago ovata seems similar to this, with almost the sole usage being promotion of defecation and relief from constipation.

The plant known as plantago ovata and the fiber component from it, known as psyllium, are commonly and effectively used to promote defecation secondary to increasing fecal moisture, size, and ease of passage

Psyllium fiber can be fractionated into three components:

• A highly (greater than 80%) fermentable component totalling 15–20% of psyllium weight^[8]

• An unfermentable (less than 20%) component comprising 10–15% of psyllium weight^[8]

• A poorly (30%) fermentable bulk-forming component constituting 55–60% of psyllium weight^[8]

Psyllium is richest in Xylose (59%) and arabinose (22.3%) while also possessing a uronic acid content (6.1%), galactose (3.7%), glucose (3.5%), rhamnose (3.0%), mannose (1.6%) and barely detectable ribose content (0.01%).^[8]

The unfermentable (and to a degree, poorly fermentable) components of psyllium underlie the gel forming and fecal forming properties of psyllium supplementation^[9] and psyllium in general appears to collect 2-3g of water per gram of psyllium.^[10]

Psyllium fiber is comprised of indigestible carbohydrate chains (fibers) and can be fractionated into different fragments based on polarity, the one consisting of most weight being both poorly fermentable in the colon while also being highly gel forming (and the fraction causative of fecal forming properties)

It is sometimes stated that the absorption of water in the intestines associated with psyllium may cause an appetite suppressing effect^[11][12] Mechanisms by which fiber may affect appetite include release of intestinal peptides involved in energy regulation^[13] of which the increase seems comparable to protein on a gram per gram basis,^[14] reducing the weight of gastric emptying,^[15][16] or modifying postprandial (after meal) glycemic response and regulated the interactions of carbohydrates and appetite.^[17][18]

20g of psyllium husk 3 hours prior to a meal and then again immediately prior to the meal (200mL each time, relative to placebo and control with same amount of water) significantly increased meal-induced satiety as assessed by a visual analogue rating scale^[19] with another study using a breakfast containing psyllium husk at 17.6g noting that it was more effective than placebo breakfast at suppressing appetite in healthy weight males, but trended to underperform relative to wheat bran (17.6g).^[20] This study failed to note a decrease in whole-day energy intake, but merely a delay of the time until the next meal occurred.^[20]

A study assessing the threshold of psyllium fiber required to reduce appetite (using fiber containing wafers prior to a standardized test meal) noted that 3-8 wafers (conferring 1.7-4.5g psyllium) were ineffective while 13-18 wafers (7.4-10.2g psyllium) reduced subsequent food consumption by 169 and 234kcal respectively; this study is complicated with the inclusion of other nutrients (carbohydrate) during wafer consumption.^[1]

Appetite suppression has been noted with psyllium supplementation, although it does not appear to be of remarkable potency (one study noting acute appetite suppression failed to find a reduced caloric intake over the course of the day) and occurs at higher doses, around 20g of psyllium taken before or with a meal

Due to the low potency and high dose required, psyllium may not be a practical appetite suppressing intervention (and should be taken for other purposes, with the knowledge that appetite may be suppressed slightly)

Some studies (animal models) have noted increased fecal fat content associated with psyllium relative to control, indicative of inhibiting lipid absorption.^[21]

One small study in otherwise healthy persons using 25g daily with a highly restricted diet failed to note universal reductions in lipid absorption, with one out of four subjects experiencing no such reduction.^[22]

At least in guinea pigs, increasing vitamin C content in the diet from normal (0.05%) to elevated concentrations (0.5%) alongside psyllium ingestion appears to enhance the triglyceride lowering effect of psyllium intervention in animals fed a high fat diet.^[21] This study noted that, comparatively, 10% psyllium underperformed 5% chitosan in reducing serum triglycerides in response to a fat-rich diet in guinea pigs.^[21]

Some possible triglyceride lowering effects are noted in animal studies

For human interventions, 5g of psyllium thrice day with meals for 6 weeks in diabetics is associated with a 26% reduction in triglycerides relative to placebo.^[23] This reduction in triglycerides has been noted elsewhere in diabetic men given psyllium^[24] although no effect has been seen in youth given 6g of psyllium for six weeks (without hypertriglyceridemia).^[25]

When assessing persons with high cholesterol, a meta-analysis failed to find evidence for a triglyceride lowering effect.^[26]

Some evidence suggests a triglyceride lowering effect in diabetic persons, although overall and when assessing persons with high cholesterol there does not appear to be a significant effect on triglyceride levels in serum

As psyllium husk is able to bind to bile acids in the intestines and promote their excretion (via defecation), the efflux of bile acids from the liver is met with an induction in mRNA content of heptic cholesterol 7R-hydroxylase, the rate controlling enzyme in bile acid synthesis.^[27][28] This upregulation of bile acid production uses cholesterol as a substrate, and is thought to be the main mechanism of cholesterol reduction via dietary fibers^[29] including both bran^[30][31] and psyllium.^[2][32]

The bile acid binding property is independent of short-chain fatty acid production (may occur from fiber fermentation in the colon) as it occurs in rats without a colon^[8] and is directly related to the viscosity of the fiber, as when separating the gel-forming portion of psyllium from other fragments only the gel forming fragment is able to increase fecal bile acid content.^[8]

Alongside fatty acids, bile acids are also lost in the feces following ingestion of psyllium husk (and other fibers). As bile acids are required in the liver, the creation of them in order to replace what is lost goes up, and cholesterol is reduced as cholesterol is used as substrate to synthesize bile acids

In studies assessing HDL-C in animals, psyllium appears to fully normalize the reduction in HDL-C seen with a high fat diet^[21] and improvements in HDL-C have been seen in humans (diabetic) consuming 5g of psyllium thrice a day for 6 weeks where HDL-C rose 45.7% higher than placebo.^[23] However, a meta-analysis of psyllium supplementation in hypercholesterolemic patients has noted a small but significnat redution in HDL-C cholesterol associated with supplementation to the magntiude of 0.0353 mmol/L (95% CI of 0.0003–0.0514 mmol/L).^[26]

A meta-analysis of psyllium in 1030 persons with high cholesterol has noted that psyllium tends to be associated with a reduction in total cholesterol by 0.375mmol/L (95% CI of 0.257-0.494mmol/L) and LDL-C by 0.278mmol/L (95% CI of 0.213-0.312 mmol/L) which appeared to follow both dose dependencey (with greater increases with 20.4g relative to 3g, the range of the assessed studies) and time dependency, with longer supplementation periods being associated with greater decreases.^[26]

This meta-analysis, when comparing the effects of studies using psyllium in supplemental form versus enriched food products, noted no significant difference between the vessel by which psyllium was delivered.^[26] It also noted evidence of publication bias but attributed this to a phenomena of small trials (in regards to statistical robustness) possessing greater effect sizes.^[26]

Psyllium husk supplementation appears to be able to reduce both total cholesterol and LDL-C in persons with high cholesterol in a dose and time dependent manner up to 20g of supplementation (highest dose assessed), although it does not appear to have a beneficial effect on HDL-C and instead reduces it to a small (perhaps clinically insignificant) degree

An 8 week study with four groups (low or high protein paired with low or high fiber; psyllium at 12g was used on top of 15g of fiber from the diet) noted that psyllium was effective in reducing ambulatory blood pressure in hypertensive persons and that this benefit was additive with increasing dietary protein (12.5% of calories up to 25%); only combination treatment came back significant, however.^[33] This was followed with a study in overweight and obese persons comparing psyllium supplementation (7g) against placebo (with a third group given exercise with placebo) where psyllium was associated with a 7% reduction in both systolic and diastolic blood pressure after 6 weeks with occured alongside a 22% reduction in the Augmentation Index (assessment of vascular function); although benefits were present at 12 weeks, they were no longer statistically significant.^[34]

In youth (obese but not hypertensive), there is not a significant reduction in blood pressure.^[25]

Consumption of psyllium (3.5g) with a test breakfast (436kcal; ham and two slices of bread) is associated with an average 12.2% less glucose absorption when tested after 6 weeks of psyllium usage (although a fair bit of variation was observed between persons), this decreased glucose absorption did not occur 4 weeks after supplement cessation suggesting acute effects.^[35] This study, as well as another study in healthy persons given test meals with or without psyllium supplementation, note a decrease in the rate of glucose absorption^[14]

This variation between individuals is consistent with dietary fiber in general,^[36] and although the reasons for variation are not known (thought to be related to baseline characteristics or diet overall) the glucose lowering effect is thought to be related to viscosity^[37][38] (and mixing of carbohydrate with the intestinal gel causing slower release^[39]) and is reliant on carbohydrate coingestion.^[40]

(Soluble) fiber in general, and by extension psyllium, appears to cause gel formation in the small intestine and cause a reduced rate of glucose absorption and by extension lower glucose concentrations in serum. Psyllium has not been associated with increased fecal content of glucose (indicative of preventing absorption of glucose)

In diabetic mice fed 3.2% of their diet as psyllium for 18 weeks, psyllium was able to reduce fasting glucose (20%) in diabetic mice with no effect on non-diabetic mice.^[41] Psyllium has also been confirmed to reduce blood glucose in Zucker rats (prone to diet induced obesity and subsequent metabolic complications).^[42]

A few studies have been conducted in diabetic persons under metabolic ward conditions where diet was controlled, with one noting a 11% decrease in glucose (AUC over the entire day) and 19.2% reduction in post-prandial glucose with once daily 5.1g psyllium over 8 weeks^[43] and 5g thrice day psyllium with a standarized diet (25kcal/kg and 50% carbs with 1g/kg protein) noted a 29% reduction within 2 weeks with no further benefit over 6 weeks;^[23] both studies occurred independently of weight loss.

Similar reductions in blood sugar have been noted in both diabetic and non-diabetic obese patients (higher blood sugar than lean controls)^[3] and higher doses of psyllium (14g daily for 6 weeks) do not appear to have more benefit than lower doses (5 daily).^[35]

One meta-analysis has concluded that psyllium husk may be an effective adjuvant treatment for diabetics who keep complications with blood glucose following drug therapy due to the reductions in blood glucose and HbA1c associated with an average 10.6g psyllium daily and high safety profile.^[44]

Psyllium husk treatment appears to be effective in reducing blood glucose concentrations, but may not provide a lasting effect on blood glucose (with glucose normalizing after supplementation is ceased). It may be useful to be taken alongside other supplements or drugs for persons with diabetes as the potency of psyllium does not appear to be of the level where it alone can provide sufficient help but has a large enough safety profile that drug-drug interactions are not a large concern

14g of psyllium (3.5g taken thrice a day) for 6 weeks is associated with reductions in HbA1c dependent on treatment (3.8% after 6 weeks treatment, which normalized to 5.5% 4 weeks after usage)^[35] This reduction in HbA1c has been noted in a meta-analysis with an average daily dose of 10.6g psyllium in diabetics although to a low magnitude.^[44]

A decrease in urinary glucose (22.5%) has been associated with psyllium supplementation.^[35]

Studies measuring serum insulin do not tend to note many significant differences associated with 6 weeks of 14g psyllium daily.^[35]

May reduce HbA1c transiently and does not appear to have a significant effect on serum glucose

When a mixed meal is consumed with additional psyllium husk, there does not appear to be any significant differences in after-meal thermogenesis between psyllium and control.^[45]

In human interventions, there has been no significant effect of 5g of psyllium taken thrice a day for 6 weeks on the body weight of diabetics independent of changes in diet^[23] and one review^[12] assessing long term studies using up to 15g of psyllium daily without a coingested hypocaloric diet failed to find any evidence of weight loss associated with psyllium intake despite other benefits being present.^{[23][46][47][48][49]}

For studies with weight loss as a primary end goal, psyllium at 'two tables spoons thrice daily' (exact dose not stated) over 150 days in obese persons in a pilot study without controlled diet noted a weight reduction of 5% (no placebo or control group) which underperformed relative to Orlistat and subitramine.^[50]

There does not appear to be sufficient evidence to support the usage of psyllium supplementation for the purpose of weight loss

When assessing the skeletal muscle following consumption of dietary psyllium, an increase in GLUT4 protein content in the plasma membrane of spontaneously hypertensive rats^[51] and may be related to reductions in overall glucose AUC (as no malabsorption of carbohydrate is noted) in Zucker rats^[42] and humans consuming psyllium at 3.5g four times daily (14g total) for 6 weeks.^[35]

Mechanistically, there does not appear to be influence on PI3K^[51] (activated following activation of the insulin receptor) and an influence was noted in plasma but not intracellular membranes; cellulose was not involved with increasing GLUT4 content^[51] and the authors hypothesized this was related to short chain fatty acid production in the intestines from fiber fermentation (seen with other fiber sources^[52]) possible via acting upon PPARγ.

An increase in GLUT4 content in skeletal muscle may underlie reductions of blood glucose seen with psyllium supplementation, as carbohydrate malabsorption does not appear to be present following consumption of psyllium (suggesting peripheral effects). Preliminary research at the moment

One study using rats fed a high fat diet or a high fat diet with psyllium (5% of diet) noted that the reduction in genes involved in fatty acid oxidation (in skeletal muscle) associated with a high fat diet was attenuated, manifesting as a relative increase.^[53]

In regards to the three possible 'fragments' of psyllium, the gel forming fragment (55-60% of psyllium by weight) appears to be very poorly fermented (up to 30% fermentation over 72 hours)^[8] although the other portion of psyllium does appear to be fermentable; the short chain fatty acids (acetate, propionate, i-butyrate, n-butyrate, i-valerate and n-valerate) have been noted to be produced from psyllium in ex vivo fermentation^[8] and has been attributed to the high arabinose content of this psyllium fragment (arabinose is relatively less fermented than other monosaccharides such as xylose^[54][12][55]) but also to the structure of psyllium's carbohydrate chains, which are highly branched (α-L-arabinofuranose side chain units and some complex heteroxylans sidechains) on a linear β-D-(1–4)-linked xylopyranose backbone.^[56] Although SCFAs are produced from psyllium, it is comparable less to other fiber sources (outperforming only Inulin) and is relatively high in acetate (propionate and butyrate production comparably less)^[57] and similar to other fibers fermentation is not seen in all human stool samples due to variance in intestinal bacteria.^[58]

Multiple other studies conducted on psyllium fermentation note that it is resistant to fermentation and never fully fermented by various bacterial strains native to the human intestinal tract,^[59][60][57] and it has been noted that most of this limited fermentation occurs within 4 hours and plateaus at 24 hours.^[57][61]

This poor fermentation has been noted elsewhere with the bacterial strain Bacteroides ovatus V975 where the poor fermentability of both psyllium and fenugreek fiber were said to underlie their ability to increase fecal roughage^[62] (as with less fermentation in the colon comes a retention of gel forming properties; fermentation of the fiber destroys its structure and the gel forming properties would be lost)

Due to the structure and sugar composition of psyllium, the gel forming fragment (comprising the majority of psyllium by weight) is poorly and incompletely fermented in the colon by intestinal bacteria. This allows a retention of gel-forming abilities in the colon and subsequently increases fecal roughage, but this fermentability results in less short chain fatty acid production (which are one of a few mechanisms linking systemic health effects to colonic bacteria)

Despite the aforementioned poor fermentability, some degree of short chain fatty acids (specifically, butyrate) have been found in the feces of subjects consuming 10g of psyllium husk twice daily.^[63]

The small portion of psyllium that is able to be fermented has been confirmed to do so in humans

Psyllium husk given alongside test meals (23g) in otherwise healthy persons is able to attenuate the rate of release of ghrelin and PYY with a suppression in GLP-1 release rate.^[14]

Similar to other soluble fibers, psyllium husk is able to normalize an excessive intestinal stool passing time (frequency greater than once a day and overall transit time less than 3 days) to a fairly normal one (frequency of approximately once a day, transit time greater than 3 days; this study used bran^[64]) although psyllium appears to be unique in the aspect of water resportion paired with low fermentability, where it is known to create a stool that is softer and easier to pass^[22][65][4] (such as in comparison to wheat bran, where psyllium is associated with less 'hard' stool^[66]) without significantly affecting large bowel physiology.^[67] Psyllium acts as a 'bulk laxative' (laxative agent that works secondary to increasing fecal weight and promoting defecation) and due to water resorption appears to lubricate itself.^[9]

One study noted comparable efficacy between psyllium supplementation and a combination of cellulose and pectin for fecal formation;^[65] as cellulose is a common indigestible fiber in fruits and vegetables, this study suggests pectin-containing food sources may be equally efficacious.

Psyllium can have a slight prolaxatative effect in instances of constipation (nowhere near the potency of laxative compounds such as caffeine or Senna alexandrina) while having anti-motility actions in periods of excessive defecation. Stool tends to be softer when passed when psyllium is in the diet

Numerous studies comparing psyllium to control animals have noted a quantitative increase in fecal weight and moisture content independent of changes in food intake, due mostly to increased water resorption in the colon.^[21] This has been demonstrated in humans assessed by fecal analysis following oral consumption of psyllium husk^[65][66] with one study noting two out of four subjects experiencing a doubling of fecal weight.^[22] In a rat model of Colectomy (Colon removed, the moisture content of feces in this rat model at 65-70% better mimicks human moisture content at 70-75%; normal rats reach 12-55%^[8]), ingestion of either whole psyllium or the gel forming fragment can increase moisture content from an expected 65-70% to 86-90%.^[8]

The water resorbing and fecal forming properties appear to be based upon one poorly fermentable and gel forming fragment of psyllium.^[65][8]

Psyllium is able to resorb water in the intestines and increase the weight of feces, which is a mechanism thought to underlie the ability to pass 'softer' stool

Fiber in general promotes flatulence independent of health state^[68][69] secondary to slowing intestinal motility and causing gas buildup.^[70] Psyllium appears to produce less gas (flatus) relative to other fiber sources (such as xylan and pectin^[71]) with some studies suggesting no increase in gas production associated with psyllium supplementation.^[72][73][74]

Gas production in the intestines occurs secondary to bacterial fermentation of fibers^[57] although there appears to be a discord between psyllium and flatus (with low, but present, fermentation and unexpectedly lower flatus production following psyllium ingestion).^[75][71][72]

One study using 30g of psyllium with a meal and measuring flatulence (intrarectal catheter) relative to no fiber control has noted a decrease in flatus independent of any effect on farting flow rate, volume (physical property rather than audio), pressure, or duration.^[70] The authors hypothesized that this was related to fecal absorption of gases (which may contribute to the known 'softness' of stool associated with psyllium) and that passing stools excreted gas independently of farting.^[70]

Fiber in general is proflatus (pro- meaning increase, -flatus being a term used to refer to flatulence of farting) although psyllium appears to be less proflatus than other fibers comparatively with some studies suggesting no significant 'flatuence' related side-effects.

One study, which has not yet been replicated, has empirically measured less flatulence following a single dose of psyllium husk. It was thought that this was related to the feces absorbing gas and it being excreted independently of farting

One small (n=4) study using 25g psyllium husk daily for three weeks paired with a highly controlled diet failed to note universal effects on nutrient absorption, as one subject noted significant reductions in caloric, amino acid, and fatty acid absorption whereas two noted insignificant decreases (and one with no decrease).^[22]

Dietary fiber in general (although bran and psyllium mostly of concern) appear to be able to directly bind to dietary minerals, with psyllium being more effective in this binding than pectin and cellulose ex vivo (reaching 60% binding at pH 6.8 and 1mg/mL psyllium with 1mcg/mL iron) in conditions to mimic the intestines.^[76] Higher acid concentrations reduced the binding, and chelators of iron (Citric acid and EDTA) inhibiting this binding while Cysteine, Vitamin C, and fructose did not affect binding.^[76] This inhibitory effect on iron absorption is noted in dogs undergoing acute experimentations (measured over 4-6 hours^[77]) and in an acute intervention using psyllium via food products it was noted that psyllium has a slight but significant reduction in iron absorption acutely (four doses of radiolabelled iron, with serum measurements taken 2 weeks later to assess retainment).^[78]

The increased iron absorption seen in periods of anemia, at least in dogs, appears to persist even when dietary fiber is introduced.^[77]

In vitro and in acute experiments, psyllium appears to slightly but significant reduce iron absorption secondary to directly binding to the iron and preventing its uptake. This inhibition is markedly less than that seen with wheat bran fiber, but more than that seen with pectin (pectin, overall, is fairly inactive)

In regards to dietary minerals, one study in children (high cholesterol) with supplemental psyllium husk did not note any significant variations in circulating serum minerals (iron, zinc, and calcium) following 6g of psyllium husk daily for 4-5 weeks^[79] and this failure to modify serum iron and zinc has been replicated in men with high cholesterol following 10g daily for 8 weeks^[80] and 14g psyllium daily for 8 weeks (Iron only).^[35] A study in hypercholesterolemics using 10g psyllium or a similar amount of pectin fiber via cereal has also noted that the reduction in serum iron seen in placebo (21 to 17mmol/L) was not present in fiber groups, manifesting as a relative increase.^[81]

There do not appear to be significant reduction in serum zinc or iron following routine consumption of psyllium husk in the diet at doses of up to 10g daily for maximal periods of up to 8 weeks (higher doses and time periods not assessed), suggesting the inhibition of nutrient binding may not be practically relevant. A limitation of these studies is assessing serum iron (a marker of chronic iron stores, a transferritin reading would reflect more transient fluctuations in iron)

It has been noted ex vivo that the pH of solution containing psyllium (prior to fermentation and then allowed the limited fermentation to occur) is subsequently reduced (6.78 to 6.62; blank plate increased to 6.92) which was comparable to β-Glucan but underperformed to long-chain Inulin (6.39) and fructooligosaccharides (6.18).^[57] Fermentable fibers such as Inulin have been noted to increase mineral absorption in the colon (calcium and magnesium most researched) due to increasing pH in the colon,^[82][83] with limited evidence suggesting that this does occur with psyllium but to a lesser degree relative to Pectin.^[84]

Coingestion of carbohydrates alongside the fiber, in rats, does not appear to modify psyllium's actions on calcium absorption.^[84]

It is possible that an increase in pH in the colon secondary to the limited fermentation of psyllium (seen in vitro) can increase mineral uptake in the colon and may underlie overall null effects on mineral status in living models, but this possible mechanism has not been fully explored as it pertains to psyllium

In persons undergoing remission for ulcerative colitis, it appears that supplementation of psyllium husk seeds at 10g twice daily (for a total daily dose of 20g) is able to sustain remission with a potency comparable to 500mg mesalamine (thrice daily dosing) with the two being slightly additive.^[63]

Appears to preserve remission in persons with inflammatory bowel diseases

Consumption of psyllium (10.8g) immediately prior to a mixed test meal (445kcal) is associated with an delay in gastric emptying (3-6 hours after meal ingestion, with no difference 1-3 hours after) as assessed by echographic evaluation.^[15] This study also confirmed a high correlation (R=0.957-0.989) between the content of food in the stomach and appetite, with psyllium suppressing appetite relative to placebo only at the 6 hour mark.^[15] These effects seem to be related to the gel forming properties of psyllium, as they have been mimicked in vitro with other soluble fibers.^[85]

Consumption of psyllium (and common to all gel-forming fibers) has been associated with reduced gastric emptying rates, retaining a greater portion of ingestion food in the stomach which may influence satiety

A class of drugs known as 'floating drugs' aim to prolong the time a drug is retained in the stomach, and are used to either bioavailability (if said drug can be absorbed through the gastric wall and would be destroyed in the intestines by high pH) or targeted delivery (increases time to target gastric ulcers);^[86] psyllium is useful here since it may swell up to 14 times its initial size and has density lower than that of gastric fluid^[87] and an in vitro assessment noted that 75-125mg of psyllium husk in a capsule was associated with a reduced rate of drug release in the presence of HCl while not affecting overall release.^[87] Other studies have noted some efficacy with psyllium in this regard^[88][89][90] and are being put to use in combination with Silymarin (Milk thistle)^[91] and Licorice.^[87]

May have a role in benefitting drugs that require time exposure (AUC) in the stomach

When psyllium (10% of food by weight) was paired with high Vitamin C (0.5%) rather than normal vitamin C content (0.05%) in the guinea pig's diet that there was a trend to increase the anti-obesity effects of psyllium (failed to reach significance).^[21]

Coingestion of psyllium alongside cornstarch (source of amylose) appears to delay the rate of amylose fermentation and subsequently more fermentation is undergone in the distal colon rather than the cecum, causing a relative increase in the production of butyrate production from amylose consumed with psyllium relative to amylose alone.^[92]

In human interventions with psyllium, treatment with doses around 5-10g taken thrice a day do not appear to be associated with any significant side effects beyond sporadic and transient cramping and intestinal discomfort in some persons; these intestinal side-effects are rarely, but sometimes, greater than placebo controls.^[23][3]

Some reports exist of psyllium dust (from dropping the powder and having it disperse into the air) triggering asthmatic symptoms sometimes of fatal magntiude in persons with a history of severe asthma.^[93] Some sensitization to psyllium (assessed via IgE sensitization) has been noted in up to 12% of healthcare workers who are exposed to psyllium containing products, with a history of asthma being a risk factor;^[94] bronchial hyperreactivity to psyllium was also noted in 29% of persons.^[94] Those with documented IgE sensitivity to psyllium may (47% of persons) experience symptoms of conjunctivitis, rhinitis, or exacerbation of asthma.^[95]

Due to the above, psyllium exposure is known as a workplace occupational hazard for healthcare workers^[96][97][95] and in pharmaceutical plants that manufacture psyllium.^{[98][99][100]}

Inhalation of the fumes of psyllium dust is known to be a significant irritant and may cause broncial distress in persons who inhale psyllium frequently (medical workers) or have moderate to severe asthma, which seems to be a risk factor for psyllium induced broncial distress

The endosperm and seed embryo components, but not the gel-forming colloid, are allergenic^[101] and all components are present within fiber supplements to varying concentrations depending on processing and purity.^[101][93] Although comparatively less frequent than asthmatic aggravation via inhalation, allergies to oral psyllium containing products have been reported.^[102]

The most common method of psyllium triggered anaphylaxis appears to be via cereal ingestion from enriched food products^[103] although supplementation has been linked to anaphylaxis (workplace sensitization to psyllium may have been a factor^[102]).

Comparatively less frequent, but allergic reaction from oral psyllium supplements has also been reported