Bromelain

Bromelain is an enzyme extracted from pineapples. It can reduce heart burn and act as a nasal decongestant.

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Bromelain, also called ‘pineapple extract,’ is a combination of several compounds, including a large amount of a special protein-digesting enzyme. This enzyme is able to be digested and thus affect the blood and body, rather than just the stomach and intestines.

When Bromelain is in the stomach, it will help the body break down and digest protein. Supplementation of bromelain can also reduce nasal inflammation, meaning it acts as a decongestant.

If taken between meals, bromelain can benefit the immune system and protect the body from cancer. Bromelain’s effects on fat cells are also under investigation, with promising preliminary evidence.

Bromelain’s anti-inflammatory properties are responsible for several of its effects, including its ability to decongest the nasal cavity. Further research is needed to determine the mechanism through which bromelain survives the digestive system.

There are many anecdotes that say bromelain supplementation will cause semen to taste like pineapple, but no studies have tested this claim.

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Also Known As

Pineapple extract


Things to Note

  • Pineapple makes semen taste like pineapple according to anecdotes; Bromelain contains pineapple aromatics and may do this as well

  • Depending on why you are supplementing Bromelain, you may want to take it with a meal or without; please take note of the 'How to Take' section for dosing

  • If left in solution for too long, Bromelain might auto-digest. It would not be advisable to mix it into a drink and leave it alone for prolonged periods of time

Is a Form of


Goes Well With

  • Certain anti-biotics (see Nutrient-Nutrient Interactions), may increase bioavailability
  • Dietary protein (if suffering from dyspepsia)

Caution Notice

Examine.com Medical Disclaimer

The standard dose for bromelain depends on the goal of supplementation. If the goal is to aid digestion, the standard dose is between 200 – 2,000mg, taken with a meal.

If the goal of supplementation is not digestion related, does range from 200 - 800mg.

Bromelain is typically taken between meals to avoid potential degradation in the stomach. The large range for the standard dose is due to the variations in the enzymatic potential of bromelain, which is standardized by milk clotting units (MCU), or gelatin dissolving units (GDU).


I suffer from Rhinitus, and thus Bromelain is in my arsenal.

That is all. The other things are nice and all, and I do like the idea of an anti-cancer fat burner that also modulates immunity.

But I just want a clear nose; this and Ephedrine give me that.


Kurtis Frank

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Bromelain has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CIncidence of Type 1 Diabetes
CSymptoms of Osteoarthritis

No significant influence on symptoms of osteoarthritis when tested

CMuscle Soreness

Minor

It is possible bromelain might reduce muscle soreness, but currently the evidence does not support this claim (although the trial to note a failure of bromelain also noted... show

DNasal Congestion

Minor

The potency at this moment in time does not appear remarkable.

DInflammation

Minor

Requires more evidence, but at the moment appears somewhat effective

DSubjective Well-Being

Minor

Minor improvements in well being secondary to reducing joint pain


Studies Excluded from Consideration

  • Confounded with Trypsin and Rutin (as rutoside dihydrate)[1][2][3][4]

Disagree? Join the Bromelain Discussion

Table of Contents:


Edit1. Source and Composition

1.1. Sources

Bromelain is a crude extract that comes from pineapples, particularly the stems or immature fruits; thus Bromelain is sometimes referred to as Pineapple extract.

1.2. Composition

Bromelain is a mixture of:[5][6]

  • Thiol Endo-peptidases, such as Ananain and Comosain.[7][8] These tend to be seen as the main active components.
  • Phosphatases
  • Glucosidases
  • Peroxidases
  • Cellulases
  • Glycoproteins
  • Proteinase Inhibitors, such as Cystatin[9]

The overall mixture of Bromelain tends to have enzymatic activity on analyl, glycyl, and leucyl bonds and has a broad enzymatic profile.

1.3. Processing

Bromelain is usually produced by cooling pineapple juice and then subjecting it to centrifugation, ultrafiltration and lyophilization.[6] Alpha-macroglobulin is usually added to aqueous solutions, as Bromelain can self-digest in solution.[10][6] However, extraction can feasibly come from other sections of the pineapple such as the peels and rind.[11]

The final product is a yellowish powder which retains the aromatic properties of pineapples.


Edit2. Pharmacokinetics

2.1. Intestinal Absorption

Bromelain appears to be absorbed from the intestines and is bioactive. It is absorbed enzymatically active in the intestines of man[12] at around 40%[6] with a half-life of around 6-9 hours.[12] Oral bioavailability of bromelain has been replicated elsewhere.[6][13][14]

2.2. Circulating in Serum

Circulating concentrations of 5000pg/mL enzymatically active bromelain have been noted in vivo 48 hours after oral ingestion of 8.6g Bromelain.[12] An AUC of 2.5-4mcg bromelain is estimated between 3-51 hours after 8.6g orally ingested.[12]

While circulating in serum, Bromelain associates with the anti-proteinases alpha-2-macroglobulin and antichymotrypain.[12] Beinding to these anti-proteinases reduces the enzymatic activity of bromelain, but does not abolish it.[15]

Despite being a quaternary protein in size, Bromelain appears to be absorbed and enzymatically active.

2.3. Cytology

Bromelain appears to be able to transverse a cell membrane and retain enzymatic activity.[16][17][18]


Edit3. Digestion and the Intestinal Tract

The general idea of Bromelain and digestion, as well as the entire protease class, is that they may contribute for an otherwise impaired digestive system.[19] Bromelain has some other effects extending beyond its activities as a protease, however.

3.1. Gastric

Bromelain has been shown effective in reducing dyspepsia in persons without heliobactor pylori infections when in conjunction with other nutraceuticals.[20]

3.2. Intestinal

Via its protease activities, bromelain can slow down intestinal motility in rats and in vitro.[21] Its activities are inhibited by PAR-2 (receptor sensitive to proteases) as well as PDE4 and PLC downstream of the receptor, suggesting mechanisms of action.[21]

3.3. Colonic

An oral dose of 2-20mg bromelain in drinking water once daily is able to reduce inflammation in a murine model of colonic inflammation, and theoretically may aid inflammatory bowel disease (IBD).[22] Controlled doses of 2mg and 5mg showed benefit, although 2mg was too low to be significantly different than control.[22]


Edit4. Interactions with Immunology and Inflammation

4.1. Mechanisms

Bromelain, in vitro, can straight up remove (possibly through digesting) select receptors on T-cells; CD6-8, CD44 and an isoform of CD45, Leu8/LAM1 and E2/MIC2 are removed from T-cells after incubation with Bromelain.[18] CD2-3 and CD28 were confirmed to be unaffected. Vicariously through these receptor changes, Bromelain can increase CD2 expression (normally hindered by CD44) and increase T-cell binding to monocytes via CD2 and via mechanisms not mediated by receptors[18] the former of which are due to CD44 elimination.[23] Bromelain has previously been shown to enhance T-cell binding to autologous E rosettes[24] and is also implicated in CD36 elimination from macrophages, reducing formation of foam cells.[25]

Elimination of the receptor proteins CD128a/CXCR1 and CD128b/CXCR2, receptors for IL-8 and related molecules, also occurs after Bromelain incubation.[26] Elimination of these receptors in particular causes less neutrophil recruitment to the site of inflammation by reducing chemokine signalling efficacy.[27]

Bromelain also appears to inhibit signal transduction in T0 cells that results in inhibition of ERK2 phosphorylation and p21ras activation[28] and can inhibit the COX2 enzyme as well as reduce activation of NF-kB.[29][30]

In general, it appears Bromelain eliminates the receptors on immune cells that respond to (mostly) pro-inflammatory signals. Without this needed junction in signalling, pro-inflammation doesn't occur as much and a relative state of anti-inflammation appears to occur.

4.2. Efficacy and Potency

Doses in rats around 10mg/kg bodyweight appear to be approximately as effective as dexamethasone in some studies[31][32] and other animal or in vitro studies compare its potency against standard NSAID treatment (aspirin, diclofenac) with similar potencies.[33][34][35][36]

4.3. Inflammation and Exercise

One study conducted with protease supplementation (Bromelain and Papain) found that protease enzymes circulating in serum were able to attenuate muscle damage associated with exercise and preserve power output over time.[37] These effects have been noted before with protease supplementation in general, and seems to be more due to that property rather than Bromelain per se.[38] Protections seems to be confered against ischemia-reperfusion injury as well, although the study in question here is confounded with trypsin and rutin ingrestion.[39]

Preliminary research suggests it can reduce markers of muscle breakdown and soreness, while preserving power output. Possibly a good idea for sports athletes, although it might have to be pre-loaded

4.4. Type 1 Diabetes Risk

An in vitro study investigating the immunomodulatory effect of Bromelain noted that Bromelain was able to reduce the inflammatory insult on Pancreatic Beta-cells, and hypothesized that Bromelain could aid Type 1 Diabetes.[40] Subsequently, one small study investigated whether protease supplementation was able to reduce the risk of developing Type 1 Diabetes Mellitus (TIDM) in a population of persons who tested positive for antibodies that put them at risk for TIDM was conducted. A daily dose of 90mg bromelain (with 100mg rutinoside and 48mg trypsin) showed positive biochemical changes in immune status but did not significantly affect rate of Type 1 Diabetes development over 8 years (24 months of supplementation) in these 20 persosn.[41]


Edit5. Interactions with Cancer Metabolism

5.1. Mechanisms

In vitro and in rats, an increase in p53 expression and an increase in the Bax/Bcl-2 ratio are seen after incubation with Bromelain.[29][30]


Edit6. Interactions with Cardiovascular Health

6.1. Blood Flow

Bromelain possesses both fibrolytic and anti-platelet functioning, .

When looking at Bromelain in vitro, it appears to reduce both platelet aggregation as well as binding of platelets to endothelium[42] via its enzymatic components.[43] Bromelain is effective at inhibiting 6-11% of thrombus formation at an oral dose of 60mg/kg bodyweight in rat mesenteric vessels.[42] The fibrolytic functions are also tied in with enzymatic activity, and the two confer protective effects from artherosclerosis.[44][45]

6.2. Cardioprotection

According to a Meta-Analysis of 223 studies,[45] 3 interventions have been conducted in rats investigating cardiovascular protection from Bromelain; these studies varied in research goals investigating platelet adhesion,[42] Akt/FOXO protection from ischemia,[46] and allograph atherosclerosis.[47] Although all studies showed benefit with Bromelain supplementation with no apparent side effects, their measures and research goals varied too widely to be harmonized.[45]

The same Meta-Analysis[45] found 4 human trials investigating Bromelain and Cardiovascular health, one of which is not indexed online and is in German.[48][49][43] The studies showed promise, but had low internal validity; only one was double blinded and placebo controlled.[48]

6.3. Artherogenesis

Bromelain appears to have the ability to prevent macrophages (an immune cell) from turning into foam cells via eliminating the CD36 receptor.[25] Foam cells are pro-artherogenic immune cells which contribute to arterial plaque formation.[50]

Overall, Bromelain has many mechanisms which suggest it can be quite a heart healthy compound; mostly acting in blood vessels rather than cardiac tissue. The studies conducted on humans, however, are of lesser quality and have not since been replicated


Edit7. Interactions with Neurology

7.1. Beta-amyloid

Beta-amyloid is a protein known as the 'age pigment' due to its association with aging; it is suspected of contributing to Alzheimer's Disease.

After oral ingestion, bromelain is complexed with Macroglobulin. This complex appears to be able to degrade beta-amyloid pigmentation while Macroglobulin complexes with intrinsically produced proteins are ineffective. This is a mechanism by which Bromelain may offer neuroprotection.[51]

Interventions into neuroprotection and Bromelain have been less promising. One intervention looking at protease supplementation and Multiple Sclerosis found no significant treatment effects of oral protease enzymes.[52]


Edit8. Interactions with Obesity and Fat cells

Bromelain from Pineapple Stem (stem bromelain) has been shown to inhibit adipogenesis in vitro using 3T3-L1 adipocytes.[53] A dose-dependent suppression of triglyceride accumulation was seen up to 50ug/mL enzymatically active bromelain, in where the effects were saturated; enzymatically inactive bromelain was ineffective.[53] There was about 25% less triglycerides after treatment at this level over the 8 days of incubation, and was 30% more potent than all-trans retinoic acid and 1,25-dihydroxycalciferol.[53]

It seems to inhibit mid and late phase adipogenesis, as mRNA of C/EBPβ and C/EBPδ as well as mitotic clonal expansion are unaffected yet mRNA C/EBPα and PPARγ are suppressed, more than halfing their relative mRNA levels.[53] This inhibition of mid to late phase adipogenesis shows in late stage markers of adipocyte differentiation, as the proteins Lipoprotein Lipase (LPL), aP2, Fatty acid Synthase (FAS) and CD36 are all markedly reduced.[53] A downregulation of perilipin in these cells remained during maturation, and this inhibition stays even if bromelain is removed from the medium during late-phase differentiation.[53]

PPARγ appears to have reduced phosphorylation via Akt, although Akt phorphorylation per se is unaffected.[53] TNF-α being increased may also contribute.

Apoptosis of mature cells was seen as increasingly dose-dependent with minimal effects at 10ug/mL, moderate effects at the inhibitory saturation point of 50ugmL, and significnat apoptosis at 100ug/mL.[53]

A single but sexy in vitro study; too soon to draw any conclusions, but it looks quite interesting


Edit9. Interactions with Sinuses

Bromelain may reduce complications with acute sinusitis known as a 'stuffed nose' to a greater extent than placebo.[54][55][56] One study conducted noted that 83% of persons using bromelain had reductions in nasal inflammation as compared to 52% of the placebo.[57] Bromelain appears to reduce the length it takes to alleviate sinusitis significantly, yet combining bromelain with traditional therapy for sinusitis appears to reduce the efficacy of both.[58]

Might clear your nose if you have the sniffles


Edit10. Nutrient-Nutrient Interactions

10.1. Intestinal transport

Bromelain appears to have the ability to increase bioavailability (percent absorbed) and reduce the side-effects associated with anti-biotics such as penicillins and tetracyclins after oral administration.[6][59] When looking into Bromelain and other compounds, it appears that a general motif of protease compounds (especially Bromelain) allowing larger molecules to pass through the intestines easier. This has been shown with a 6.7-fold increase in the bioavailability of low-molecular weight heparin,[60] flurescein,[61] and reduced glutathione.[61] It's interactions on bioavailability with tetracycline are not clear, as one study found an increase in bioavailability[62] yet another did not.[63]

10.2. Phlogenzym

Phlogenzym is a brand name product consisting of Bromelain at 90mg, trypsin at 48mg and rutoside trihydrate at 100mg; usually adminstered in an enteric capsule. Several studies use this blend of enzymes rather than isolated Bromelain.[1][2][3][4]


Edit11. Seminal Implications

The most well known ability of pineapples (despite bromelain's abilities against inflammation, digestion, and pharmacokinetic profile of being a blood borne active enzyme; a possibility that was once thought impossible) is the fact that pineapples flavor semen...

The volatile components in pineapple that may contribute to flavor and aroma include a series of beta-hydroxy esters such as methyl beta-hydroxyoctanoates and hexanoates (although in isolation their smell is reported repulsive, suggesting they contribute to the taste) and octalactones, which 'express the coconut-like smell of other lactones'.[64] Other compounds that are suspect are methyl butanoates that, along with methyl hexanoate, comprise over 74% of total volatiles.[65] It is likely that some of these compounds may flavor semen.

There are no clinical trials into isolated the compound(s) that flavor semen, unfortunately.


Edit12. Safety and Toxicity

12.1. General

Side-effects with moderate to higher dosages (400-800mg) tend to be gastrointestinal in nature, including pasty feces and farting.[6] Oral administration of 500mg/kg bodyweight in rats does not seem to be associated with general side-effects.[66]

12.2. Clinical

After an attempted oral toxicity test in animals, no deaths could be seen with dosages up to 10g/kg bodyweight in rats, mice, or rabbits.[66]

Lethal doses of injections were 37mg/kg in mice and 85mg/kg in rats.[66]

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(Common misspellings for Bromelain include Bromeal, bromelin, bromelon)

(Common phrases used by users for this page include use of trypsin bromelain rutoside trihydrate tablets, rutoside trihydrate tablets assay contents, pineapple bromelain interactions, length of time to safely use bromelain, bromelain & arteriosclerosis, What can you do to help clear your artery)

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