Polysorbates

I apologize for the long wait between articles. I was working on this piece about polysorbates and my laptop died. For each polysorbate the google scholar search could only return around 20,000 results or less, roughly 70% - 80% of those are looking at different tests they can run to check that the polysorbate is present/stable/insert other quality here, or focus on nano-emulsion drug delivery. Of the remaining 20% - 30% most only mention a polysorbate as an ingredient with a fraction actually looking at what the polysorbate is doing in the body.

The lack of research on effects on our biology is disturbing given how widely polysorbates are used.
Some of the “cons” listed below can actually be good under the right circumstances.
For example using it to deliver vit C across the blood brain barrier to treat ischemia more effectively than without the polysorbate (study listed in sub-document linked below).

Polysorbates are used as surfactants and emulsifiers in cosmetics, food products, and pharmaceutical products. Oddly enough I could not locate any information on how they were invented despite the fact that they are no longer under patent protection. I can tell you that the word “polysorbate” first started showing up in scientific literature in the 50’s.

Polysorbates have two main functions (surfactant and emulsifier) and these functions are defined in the dictionary as such:

Dictionary.com defines a surfactant as the following;
“Also called surface-active agent. a substance, such as a detergent, that can reduce the surface tension of a liquid and thus allow it to foam or penetrate solids; a wetting agent.”

And an emulsifier as such;
“an agent that forms or preserves an emulsion, esp any food additive, such as lecithin, that prevents separation of sauces or other processed food.”

Polysorbates are made from sorbitol, oleic acid, and an omega fatty acid. This is true for all polysorbates, the number in the name is determined by which exact omega acid was used.
The process requires a chemical reaction between stearic acid, sorbitol, and ethylene oxide.

I did manage to find some of the history about how they became popular. Dr. Illona Purola was a cancer researcher in Finland. While she was conducting research on skin cancer she was painting the skin of multiple groups of mice with a powerful cancer causing agent, she would use a detergent on one group of mice, the mice with the detergent did not get any tumors. This prompted a year long study to see what would be most effective at preventing skin cancers and they found that polysorbates had the strongest effect. The exact process of prevention had a direct influence on hair growth. You can read about this research in detail here.
If you are losing your hair then polysorbate 80 (most effective one) may solve the issue, however more recent research can be contrasted against the previous research showing that polysorbates may have reproductive effects and Polysorbates 80 and 60 may have potential for creating tumors. The reason it affects hair growth is due to histamine release, if you suffer from skin conditions such as psoriasis or eczema then polysorbates could aggrevate these issues. The histamine release occurs for both topical and internal use.
You can read more on hair loss treatment here.

Due to the volume of literature and the fact that there are 4 separate polysorbates I’m going to try and simplify the format by addressing each one briefly and provide a link to a collection of studies for each one. If you want full access to the studies most if not all can be accessed by putting the URL of the study into this website: http://sci-hub.tw/
If that link doesn't work then you may need to google the latest version of the sci-hub url.

The effects of all the polysorbates appear to be more or less the same with the primary variation being potency. 80 seeming to be the most potent and then moving down according to number (note; the number is related to the chemical composition not the potency).

Polysorbate 80

Brand names:
Poegasorb 80
Tween 80
Alkest TW 80
PS 80
Montanox 80
SMO 80

Skin deep database rating:
3 Full assessment. Data is assessed to be “fair” but not robust.

Handbook of Pharmaceutical excipients toxicity:
Moderately toxic by injection or IV.
Mildly toxic by ingestion.
Skin irritant.
Eye irritant.
Experimental tumorigen.
Reproductive effects.
Mutagenic data.

Pros:
Helps restore hair growth.
Allows non compatible ingredients to remain mixed.
May help prevent cancer from chemical sources when used on the skin.

Cons:
Causes inflammation through histamine release.
Allows nanoparticles to enter the central nervous system (CNS).
Opens the blood brain barrier allowing drugs and other particles to enter the brain.
May cause tumor growth.
May have reproductive effects.
Allows topical substances to enter the skin that shouldn’t.
Opens tight junctions in the gut.
Prevents intestinal absorption of fats.
Capable of allowing DNA transfer
Increases permeability of the skin.

Found in:
Dryer sheets
Household cleaning products
Baby soaps
Vaccinations
Hair care products
Toothpaste
Anti-aging creams
Pet products for fur.

Polysorbate 60

Brand names:
Tween 60
LS-3058
Sorbitan, monostearate polyoxyethylene deriv
Polysorbat 60
Twen 60
Tven 60
Peg-60
PS 60
T-MAZ 60

Skin deep database rating:
3 Full assessment. Data is considered to be limited.

Handbook of Pharmaceutical excipients toxicity:
Moderately toxic by IV.
Experimental tumorigen.
Reproductive effects.

Pros:
Helps restore hair growth.
Allows non compatible ingredients to remain mixed.
May help prevent cancer from chemical sources when used on the skin.
All to a lesser degree than previous polysorbate.

Cons:
Causes inflammation through histamine release.
Allows nanoparticles to enter the central nervous system (CNS).
Opens the blood brain barrier allowing drugs and other particles to enter the brain.
Dries skin out.
Capable of allowing DNA transfer
Prevents intestinal absorption of fats.
Opens tight junctions in the gut.

Found in:
Commercially made pudding
Some household paints
Non-food pesticides
Baby skin care products
Drugstore makeup
Hair dye
Hair styling products
Sunscreen
Moisturizers
Hair care products
Dessert toppings
Cake mixes
Non-dairy creamer
Acne creams

Polysorbate 40

Brand names:
Tween 40
Montanox 40
Sorbitan monohexadecanoate

Skin deep database rating:
3 Full assessment. Data is considered to be limited.

Handbook of Pharmaceutical excipients toxicity:
Moderately toxic by IV.

Pros:
Helps restore hair growth.
Allows non compatible ingredients to remain mixed.
May help prevent cancer from chemical sources when used on the skin.
All to a lesser degree than previous polysorbate.

Cons:
Causes inflammation through histamine release.
Prevents intestinal absorption of fats.
Allows nanoparticles to enter the central nervous system (CNS).
Opens the blood brain barrier allowing drugs and other particles to enter the brain.
May aggravate propylene glycol sensitivity.
Capable of allowing DNA transfer

Found in:
Baked goods.
Cosmetics.
Textile finishes.
Ointments.

Polysorbate 20

Brand names:
Tween 20
Alkest TW 20
Durfax 20
Montanox 20
Ritabate 20
Sorbitan monododecanoate
Polyoxyethylene 20 laurate

Skin deep database rating:
3 Full assessment. Data is considered to be “fair” but not robust.

Handbook of Pharmaceutical excipients toxicity:
Moderately toxic by injection or IV.
Moderately toxic by ingestion.
Skin irritant.

Pros:
Helps restore hair growth.
Allows non compatible ingredients to remain mixed.
May help prevent cancer from chemical sources when used on the skin.
All to a lesser degree than previous polysorbate.

Cons:
Opens the tight junctions in the gut.
Causes inflammation through histamine release.
Allows nanoparticles to enter the central nervous system (CNS).
Opens the blood brain barrier allowing drugs and other particles to enter the brain.
Prevents intestinal absorption of fats.
Capable of allowing DNA transfer
Increases permeability of the skin.

Found in:
Scientific research
Some vaccines
Cosmetics
Baby care products
Household cleaners
Skin cream
Shower gel
Makeup removal cloths
Lice products
Hair dye

The documents listing studies for each polysorbate can be located by clicking on each of their names.

In summary all of the polysorbates have similar properties. Topically they are all moderately toxic but there is a distinct need for more research. By IV or injection all are moderately toxic (Lewis, RJ. Sax's Dangerous Properties of Industrial Materials. 11th. New York: Wiley, 2004). All allow foreign chemicals into the skin, CNS, and to cross the blood brain barrier.
The WHO have listed the maximum daily intake for polysorbates at 25mg/kg. Many Europeans and North Americans regularly eat 100mg of polysorbate 80 per day.
Toxicity is dose dependant and can be found in the handbook linked below.
There are other polysorbates however these 4 are realistically the only ones the average consumer will encounter regularly.

If you like to geek out you can read the full Handbook of Pharmaceutical Excipients.

Here are the abstracts from a few studies pertaining to all of the polysorbates. Some may be also located in the compiled documents linked above.

Influence of the type of surfactant on the analgesic effects induced by the peptide dalargin after its delivery across the blood–brain barrier using surfactant-coated nanoparticles

Abstract:
“The ability of 12 different surfactants, coated onto the surface of nanoparticles, to facilitate the delivery of a nanoparticle-bound model drug, dalargin, was investigated. The leu-enkephalin analogue hexapeptide dalargin was bound to polybutylcyanoacrylate nanoparticles by sorption for 3 h. Different surfactants were then coated over these nanoparticles and were injected intravenously into mice. Nociceptive analgesia was then measured by the tail-flick text 15, 30, 45 and 90 min after injection. Only nanoparticles that had been coated with polysorbate 20, 40, 60 and 80 yielded a significant effect. The highest effect was observed with polysorbate 80. Maximum effects were found after 15 min, at a dalargin dosage of 10 mg/kg, and after 45 min, with 7.5 mg/kg.”

Percutaneous Absorption Enhancement by Nonionic Surfactants
Abstract:
“The influence of nonionic surfactants (polysorbates) on hydrocortisone penetration through hairless mouse skin in vitro has been determined. Permeation was quite slow from purely aqueous media containing surfactants following finite dose application. However, if the vehicle contained high propylene glycol concentrations (40% or more), inclusion of a surfactant increased permeation rate significantly. Similar effects were noted following application of a large donor volume (infinite dose). Synergism was attributed to enhancement of surfactant absorption by the stratum corneum leading to changes in skin barrier resistance. With vehicles containing a surfactant, penetration was higher after finite dose application due to compositional changes within the vehicle.”

Evaluation of cytotoxicity of surfactants used in self-micro emulsifying drug delivery systems and their effects on paracellular transport in Caco-2 cell monolayer
Abstract:
“The objective of this study was to examine the cellular effects of the members of two non-ionic amphiphilic tenside groups and their mixtures on human Caco-2 cell monolayers as dependent upon their chemical structures and physicochemical properties. The first group of polyethylene glycol esters is represented by Polysorbates and Labrasol alone and in blends, while the members of the second group. Capryol 90, Capryol PGMC, Lauroglycol 90 and Lauroglycol FCC were used as propylene glycol esters. They are increasingly used in SMEDDS as recent tensides or co-tensides to increase hydrophobic bioavailability of a drug. Critical micelle concentration was measured by determination of surface tension. CMC refers to the ability of solubilization of surfactants. Cytotoxicity tests were performed on Caco-2 cell monolayers by MTT and LDH methods. Paracellular permeability as a marker of the integrity of cell monolayers, was examined with Lucifer yellow assays combined with TransEpithelial Electrical Resistance (TEER) measurements. The effect of these surfactants on tight junctions as evidence for paracellular pathway was also characterized. The results of cytotoxicity assays were in agreement, and showed significant differences among the cytotoxic properties of surfactants in a concentration-dependent manner. Polysorbates 20, 60, 80 are the most toxic compounds. In the case of Labrasol, the degree of esterification and lack of sorbit component decreased cytotoxicity. If the hydrophyl head was changed from polyethylene glycol to propylene glycol the main determined factor of cytotoxicity was the monoester content and the length of carbon chain. In our CMC experiments, we found that only Labrasol showed expressed cytotoxicity above the CMC. It refers to good ability of micelle solubilization of Labrasol. In our paracellular transport experiments each of polyethylene glycol surfactants (Polysorbates and Labrasol) altered TEER values, but propylene glycol esters did not modify the monolayer integrity. Polyethylene glycol esters alone and in blends (0.05% Labrasol – 0.001% Polysorbates 20, 60, 80) were able to increase Lucifer yellow permeability significantly below the IC50 concentration. On the other hand Labrasol and Polysorbates 20 have expressed effect on tight junctions of Caco-2 monolayer. It could be concluded that polyethylene glycol ester-type tensides were able to enhance the paracellular permeability by the redistribution of junctional proteins. Our results might ensure useful data for selection of suitable tensides, co-tensides and tenside mixtures for SMEDDS formulations.”

Polysorbates as novel lipid-modulating candidates for reducing serum total cholesterol and low-density lipoprotein levels in hyperlipidemic C57BL/6J mice and rats
Abstract:
“Polysorbates are amphiphilic, non-ionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan which are widely used in the cosmetic, food and pharmaceutical industries owing to these special characteristics and their low toxicity profiles. In the present study, polysorbates were investigated for their hypolipidemic activity. C57BL/6J mice and Sprague–Dawley rats were fed a high-fat diet for four weeks, then were divided into several groups, normal saline, polysorbates and positive control drugs such as lovastatin and colestyramine were administered orally to the animals for another four weeks. Complete lipid profiles of the experimental animals were determined by assessing the serum levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. The results indicate that polysorbates significantly lowered the lipid components. Polysorbates are potential candidates for preventing intestinal absorption of redundant lipid from daily intake and subsequently for preventing hyperlipidemia as well as atherosclerosis.”

Synthetic surfactant food additives can cause intestinal barrier dysfunction
Abstract:
“In addition to genetic factors and antigen exposure, intestinal barrier dysfunction plays a key role in the pathogenesis of numerous allergic and autoimmune diseases. The hypothesis of this article is that synthetic surfactant food additives (also called emulsifiers) – which are applied in relatively high concentrations in even the most frequently consumed foods – cause increased intestinal permeability, hence they can play a significant role in the increasing incidence of numerous allergic and autoimmune diseases. In many cases the surfactants added to foods are exactly the same as the ones used in pharmaceutics as absorption enhancers. Numerous synthetic surfactant food additives have been shown to increase the intestinal permeability through paracellular and/or transcellular mechanisms and some of them were also shown to inhibit P-glycoprotein. Additionally, based on the general characteristics of surfactants it can be predicted that they decrease the hydrophobicity of the mucus layer, which has also been shown to associate with increased intestinal permeability.”

Image is from pixabay and edited in canva by me