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Series Part 2: All About TOPICAL VITAMIN C ---- L-AA & Derivatives

Series Part 2: All About TOPICAL VITAMIN C ---- L-AA & Derivatives
This post will cover topical use of vitamin c and it's derivatives.
Link to the previous post.



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Topical Use of vitamin C has been proven to be beneficial in many many studies. I am quoting all the studies I could find, and listing all the benefits as well.
Topical use of Vitamin C (L-Ascorbic Acid/Ascorbic Acid) has been proven to:
  1. Help with the biosynthesis of collagen. - Anti - Ageing benefit.
  2. Help in the repair of damaged skin/ skin wounds with anti-inflammatory properties - Restore skin health.
  3. Increase the proliferation rate of fibroblasts. - Anti - Ageing benefit.
  4. Provide greater photoprotection against UV induced photoaging, immunosuppression, and even skin cancer. - Anti - Ageing benefit, - Anti - skin cancer.
  5. Inhibit the action of tyrosinase in melanocytes thus helps to make skin even-toned.- Helps with pigmentation.
  6. Restore structural and functional losses in the skin architecture associated with ageing. - Anti - Ageing benefit.
  7. Help to strengthen the lipid barrier (possibly, proven in vitro). - Restore skin health.

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There have been A LOT of studies on topical vitamin C. I have extracted and link a few I found relevant that support it benefits at THE END of this post.
There is enough evidence to believe that topically applied L-ascorbic acid is beneficial.
While most people treat Vitamin C like an acid, it's mechanism isn't exactly similar to AHA's. L-ascorbic acid is a form of ascorbic acid (vitamin C) that is recognisable as vitamin C in the skin. Topical use adds to the existing concentration of Vitamin C in the skin.
Thus, once it penetrates into the skin, it cannot be washed off/neutralised. However, some actives applied togetheat the same time can change its performance/form.
L-ascorbic acid is a hydrophilic charged molecule so it doesn't easily penetrate our lipid (hydrophobic) barrier. For optimal penetration of the epidermal barrier, aqueous formulations of ascorbic acid must be at a pH which is below the pKa (4.2) of ascorbic acid itself. Thus, L-ascorbic acid must be formulated below the PH of AT LEAST 4 for it to penetrate in our skin.
Although ideally around 3-3.5 increased penetration without excessively compromising the skin barrier.
The prime concentration depends on the formulation and associated delivery method. It is a general agreement that concentration needs to be more than 8% to be bio-available and effective. According to this study, varying concentrations from 5% to 30% were applied to pig skin(similar integumentary system approach).
It was observed that vitamin C concentration was maximum at 20% and anything above 20% surprising cause depletion in tissue concentration levels. Thus anything below 8% and above 20% is usually seen to be sparse or superfluous.
There are many stability issues with L-ascorbic acid solutions. An L-ascorbic acid solution is highly unstable and is prove to oxidation to dehydroascorbic acid(DHAA) and degradation to 2,3-diketogulonate in high temperature, light, heat, high ph, presence of oxygen and catalytic amounts of metal ions. This makes the solution progressively turn in colour from clear to yellow, to deeper shades of orange as it continues to degrade.

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  • Now the question comes: is dehydroascorbic acid (DHAA) bad for our skin?
The answer is No and Yes.
Ascorbic acid or ascorbate in its ionised form is called L-ascorbic acid. Our skin recognises L-ascorbic as ascorbic acid. Our body (and skin) also contains an oxidised form of ascorbic acid which is Dehydroascorbic acid (DHAA). A high amount of vitamin C found in normal skin is in the form of dehydroascorbic Acid. This study shows that DHAA penetrated faster than L-ascorbic acid even. DHAA may not necessarily be bad and can be converted back to ascorbic acid in the presence of glutathione & thiol-containing reducing agents such as cysteine, homocysteine, 2-mercaptoethanol, and DTT, already present in our body. However, in the presence of water DHAA may be irreversibly hydrolysed to 2,3-diketogulonate and further degrade to Erythrulose. Erythrulose is a chemical used in fake tanning.
But “Aap Chronology Samajhiye” with this representation -

https://preview.redd.it/ipk7xxd87ar51.png?width=1306&format=png&auto=webp&s=b353acd40e51fbe1a80e72d94f3e4e2a8c771cd7
L-AA is first oxidised to DHAA (which can be reversed in our skin). Oxidation means a reaction with the free form of oxygen molecules. Remember we learnt this in the last post. So oxidation can happen if L-AA is exposed to UV/oxygen in the environment at high temperature. However, DHAA can be reversed to AA in our skin because the presence of network antioxidants like glutathione that's already present in your skin. Check out this diagram to understand how that works. However, when DHAA comes in contact with water it hydrolyses to 2,3-diketogulonate. Which cannot be turned back into AA due to the 5 hydrogen ring rupture. L-AA will not directly convert to 2,3-diketogulonate. It has to first oxidize then hydrolyse.2,3-diketogulonate may be further converted to other byproducts by other processes.
Lab muffin made a post on this.
It is possible that DHAA may not convert to Erythrulose in our skin.
In conclusion, there is a lot of ambiguity around oxidised L-ascorbic acid and further processed byproducts.
No studies have evaluated the benefits and side effects of these oxidised and degraded compounds.
Although, the presence of antioxidants like ferulic acid, glutathione, vitamin e, etc. has been shown to increase the stability and efficiency of L-ascorbic acid serums. These called network antioxidants because of this reason. Again check out the diagram linked above to understand more.
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To improve stability, the delivery mechanism also plays an important role. The right delivery mechanism can help prevent oxidation and conversion to other forms. Novel delivery mechanisms may also improve penetration along with stability. New delivery mechanisms to deliver L-AA without oxidizing are bein developed. This study advocates using liposomal technology patented by Sesdema to deliver sodium ascorbate deeper into the skin. Many skincare companies are developing new anhydrous bases to disperse L-AA to prevent oxidation. Here is another study of a new delivery mechanism.
However, an independent comparative study comparing different forms and delivery mechanisms of topical ascorbic acid has not been conducted.
So in conclusion:
  • For L-ascorbic acid formulations in an aqueous:
    • Must be formulated to be below PH 3.5 or below.
    • Must be formulated using oxygen-impermeable packaging and stored at low temperature.
    • Must be at a concentration above 5-8% and below 20%.
    • Addition of other antioxidants can help improve the stability of the formulation.
    • Must be stored in a dark/light-proof packaging at a stable temperature of 25 celsius or below.
    • Must be used up quickly once exposed to ailight.
    • Addition of penetration enhancers may help improve results.

  • For L-Ascorbic acid in a Non-aqueous solution:
    • Must be formulated using oxygen-impermeable packaging and stored at low temperature.
    • Addition of other antioxidants can help improve the stability of the formulation.
    • Must be stored in a dark/light-proof packaging.
    • Performance varies with the efficiency of delivery mechanisms.

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Owing to these stability, penetration and delivery issues with L-Ascorbic acid formulas, new derivatives of Ascorbic acid were developed.
Now my field of experience is not even remotely linked to bio-chemistry so I am not going to go in detail about the biochemical pathways that are hypothesised for their efficiency. I will, however, try to compare popular derivates and their performance/properties in brief based on information available on the internet.
A comparative analysis of various Vitamin C Derivatives
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Let's be honest that picking one among the sea of options is intimidating. Fairly, it comes down to personal preference and availability.
While choosing though there are certain things you should keep in mind. Only L-ascorbic acid has been studied for over 40 years now and has consistently proven to be advantageous topically.
Due to its highly unstable nature,
  • It is best to keep all your water-based L-AA carefully protected. I
  • Ideally, they should be stored in a place with a stable temperature (in the fridge) and away from light. The smaller the quantity size the better.
  • Once oxygen touches the formula it starts to become unstable and turn yellow, making it very important to screw the lid tightly. The more product you use; the more the leftover product oxidises. Some people recommend transferring them in smaller bottles. I, apart, found that it gets tiresome to clear, sanitize bottles and dry old bottles ever. Any remains of LAA will oxidize and adding fresh batch in oxidised bottled can spoil the new batch.
Using waterbased L-AA requires some commitment and care. I love the effects though. Personally, I will walk the mile for those benefits.
Anhydrous variants are another great option. There are some limitations with anhydrous versions as well though***.*** Since AA is acidic and gritty in itself, these formulas can sting and sensitize your skin. Many people break out while using high concentration L-AA for the first time. Its highly acidic nature can compromise the skin barrier. It's best to start with a lower concentration and gradually make your skin acquainted to L-AA. This can also be achieved by using L-AA a few times a week in the start and adding barrier healing skincare products to your regime.
Most people experience a slight stinging when they use L-AA based products. There is a difference between stinging and burning although. If your skin feels like it's burning, it's best to step back, stop use and choose a diluted version/low concentration formula.
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  • The question comes: How to differentiate between stinging and burning?
Stinging is a sharp, short term, tingling sensation associated due to the low ph. It can last anywhere from a few seconds to a minute. Skin doesn't itch, turn red or feel sensitive to touch post that duration. This sensation may be experienced every time you apply L-AA but the intensity may reduce over the period.
Burning is a strong irritation that feels different from tingling. It is a strong discomfort which may be coupled with redness, itching and touch sensitivity. It basically feels like your skin is on fire. Please immediately wash your face with water to wipe off remains of the product and apply soothing, gentle products containing restorative ingredients like aloe, snail mucin, ceramides etc.
It is best to patch test L-AA based products before applying it all over the face to understanding the way it reacts with your skin. Our mod u/avaale has made an amazingly detailed guide about patch testing. Please check it out to understand more about patch testing.
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In conclusion, L-AA may not be the best option for everyone due to its stability and skin sensitizing issues. If that is the case, you can still get some benefits by incorporating vitamin c derivatives. There is a catch though. Not all derivates are equal and not enough comparative studies have been conducted to conclude which one is the most superior form.
However, by understanding the nature of the ingredient coupled with the anecdotal evidence we can understand a few things:
  • Some derivates are lipophilic/ amphiphilic so they dissolve better in lipid formulations. These formulations may include oils, butter and silicones.
  • While each formulation differs from another due to the choice of base ingredients. Some base lipids may be balanced to reduce the likeliness of comedogenicity and therefore may be less likely to cause breakouts in acne-prone skin type. Others may not suit your skin type.
  • The concentration of active ingredient plays equally an important role.

  • Pick a formula that works with your skin type, condition and goal.
    • Concentrations at which Ascorbyl palmitate ( AA-PAL) is used are extremely low. While vitamin C has shown some effects at concentrations as low as 1% but at the benefits of that concentration aren't hugely significant. When using derivatives in those concentrations, keep in mind that the derivative needs to convert to Vitamin C in your skin and some strength may be lost in the conversion. Coupling that with its stability issues, Ascorbyl palmitate doesn't catch my interest.
    • Sodium Ascorbyl Phosphate (SAP) & Magnesium Ascorbyl Phosphate (MAP) are more stable than AA-PAL but face the same roadblocks when it comes to formulating restrictions on concentration. Poor penetration and unreliable conversion don't benefit their case point. However, if acne is a pre-existing condition that you are dealing with, SAP may be an option to consider since there are some studies that support its anti-acne benefits. MAP is generally considered a better option in the industry than SAP from the overall vitamin C benefit perspective.
    • Ascorbyl Glucoside is a better option than the ones I discussed above. It is stable at a variety of pH. Thus, it can comfortably be used by with sensitive skin. It can be incorporated in a liquid wateserum-based or formulated in a cream/gel base. It has been proven to convert into vitamin C in the skin and has been proven to have some anti-ageing benefits. However, potency is still questionable due to concentration restrictions. If you prefer easy of use and elegant- textured cosmetic products, this derivative may be considered.
    • Tetrahexyldecyl Ascorbate is a newer derivative. It has not been independently researched much. There is this one study in a formula that also contained AA, which advocates it's benefits. In general, this derivative is unique due to its chemical structure and properties. Manufacturer claims suggest that it seeps in deeper into the skin than L-AA and stays in the skin 40-80% longer than L-AA. ( I am not sure if I can link/upload manufacturer documents I found through some sources and digging so if you are curious, watch out for my Instagram stories). Overall this ingredient is popular in Japan for its whitening properties and its lipid solubility puts it in an advantageous position to penetrate through the stratum corneum into the epidermis and the dermis. There is some anecdotal evidence that supports the claim that it may be one of the best derivatives out there. I also found some very expensive luxury skincare brands using this ingredient (will be sharing those insights on Instagram as well; May make a separate post if I am not being lazy).
    • Last, but not least is 3-O-Ethyl Ascorbate. It is one of the newest kid in the lot. Experts think it's structurally the closest to AA. It is an Ethylated form of AA so it's both water and lipid-soluble. Stability tests have shown it's a very stable derivative at a PH of 5. Thus, the shelf life of EAC formulated products should be longer than others. Manufacturers and cosmetic companies claim that it provides similar benefits of L-AA is not better, without the stability issues. None of these claims has been verified although. It has shown to provide some de-pigmenting and antioxidant benefits by manufacturers in vitro trials. It can be formulated using high concentrations thus, it's another derivative to watch out for.
So, which one is perfect for you? YOU decide that.
This chart may help you come to some conclusion:

A graphical representation to make your decision easier.
Another important detail: Almost all vitamin C formulations stay in your skin for up to 72 hours. Metals like iron and copper are known to destabilize and cause unwanted biochemical reactions with AA. Thus is it best not to use copper peptide formulation with vitamin C to maximize their benefit. By not using Copper peptide, I mean not just applying them together at the same time but also not using them in the same duration. So if you wish to use copper peptide you can rotate by using it for the first 3 months of the year and next three months using vitamin C and so on.

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Some Extracts with Links to Clinical Studies/Research Journals I found relevant that support the benefit of topical application of L-AA:
23.8% L-ascorbic acid and a chemical penetration enhancer consisting of N-methyl-2-pyrrolidone and dimethyl isosorbide with iontophoresis to maximize amounts of L– ascorbic acid delivered were applied once daily, in a split-face study on twenty females (Fitzpatrick type III & IV to study the effect of Vitamin C on photoaged skin. Sixteen of 20 patients (80% experienced a score decrease of 2 or 3 grades, according to the dermatologist. Fifteen patients (75%) rated their overall satisfaction as excellent or good. Dyspigmentation, surface roughness, and fine lines on the treated side improved significantly.)) Topical 23.8% L-ascorbic acid serum is effective for the treatment of photo-aged skin and does not cause any obvious side effects. Link
A double-blind randomized trial was performed to evaluate the clinical effects and the modifications of skin relief and structure over a 6-month period of use of a cream containing 5% vitamin C (Active C®, Laboratories La Roche Posay, 92407 Courbevoie Cedex, France on photoaged skin. Twenty healthy female volunteers aged 51-59 years (mean ± SD = 55.3 ± 2.8 years, were chosen for this study. Skin regions that presented with signs of ageing, the low-neck and dorsal aspects of both forearms/ the left or right half of the upper chest and the corresponding forearm were randomly assigned to once a day application of a fingertip unit of either 5% vitamin C cream or excipient alone. Each patient received a randomized pair of identical-appearing tubes, colour-coded and labelled right or left. Among these 20 patients, 10 accepted to be biopsied on both forearms at the end of the trial, after 6 months of treatment.)) Concluded that topical application of 5% vitamin C is an effective and well-tolerated treatment for improvement in the appearance of photodamaged skin. Prolonged topical treatment with ascorbic acid, applied in an appropriate vehicle, may result in activation of a dermal synthesis of elastic fibres. - Link
Fifty female volunteers aged 30‐65 years were allocated one capsule containing vitamin C (20% w/w, vitamin E, and European raspberry (Rubus idaeus leaf cell culture extract of serum for topical application on one side of the face for 2 months, in addition to self‐use of facial skin products to evaluate the anti-ageing and brightening effects of an encapsulated serum.)) ***The study evaluated improvements in skin ageing, pigment appearance, and skin integrity but no no significant improvement of skin moisture or TEWL was observed. Link
Nineteen volunteers between age 36 to 72 years belonging to Fitzpatrick skin types I, II & III were included in a 3-month, randomized, double-blind, a vehicle-controlled study that uses a product Cellex ( L-AA serum to analyse its effect on photodamaged skin topography.) A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin - Link, Link
500 mL portions of vehicle; 0.5%transferulic acid; 15% L-ascorbic acid, 1% DL-a-tocopherol, and 15% L-ascorbic acid, 1% DL-a-tocopherol, 0.5%transferulic acid were applied to patches of back skin (7.5 x10cm daily for 4 days. A 1000 W solar simulator fitted with a WG295 Schott filter to eliminate wavelengths less than 295 nm delivered UV radiation to the skin’s surface through a liquid light guide at an intensity of 5 mW per cm2of UVB and about 40 mW per cm2of UVA as measured by a radiometer. MED(Minimal Erythema Dose was determined as the lowest dose resulting in erythema with perceptible borders (40 mJ per cm2)of UVB). Each patch was given solar-simulated irradiation in triplicate from 2x to 10x MED at 2x MED intervals. An evaluation was carried out 24 h later. The combination of 15% L-ascorbic acid, 1% a-tocopherol, 0.5% ferulic acid provided approximately 8-fold protection and was statistically different than ferulic acid alone or the combination of vitamins C and E. - Link ; Check this if you want to learn more about MED testing.
Two different solutions were applied (2mg/cm2 to the back skin of human volunteers daily for four days. One solution was an aqueous solution containing 15% L-ascorbic acid, 1% d-tocopherol and 0.5% trans ferulic acid (C E Ferulic; the other, a vehicle control solution. On day four, solar-simulated ultraviolet radiation, passed through a WG295 Schott selective UVB band high pass filter to eliminate wavelengths less than 295 nm was administered to each patch of treated skin. The vehicle patch received 2-6x MED and the C E Ferulic patch received 2-10x MED of solar-simulated irradiation, each at 2x MED intervals. One day later, skin was evaluated by colorimeter for erythema and biopsies of 6x MED-irradiated skin were evaluated for sunburn cells. Each spot and adjacent unirradiated skin was measured in triplicate. The difference between irradiated and unirradiated skin determined the erythema. Sunburn cells were determined in formalin-fixed 8mm punch biopsy sections stained with hematoxylin and eosin.) C E Ferulic provided substantial protection against erythema.) Link
Dermal papillae is the structural junction between the dermis & the epidermis. It has been observed to flatten out with age. The influence of ageing on the density of the functional entities of the papillae containing nutritive capillaries, here in terms as the papillary index, and the effect of topically applied vitamin C were investigated by confocal laser scanning microscopy (CLSM in vivo. There were significant decreases in the papillary index showing a clear dependency on age. Topical vitamin C resulted in a significant increase of the density of dermal papillae from 4 weeks onward compared to its vehicle. Reproducibility was determined in repeated studies.) Topical vitamin C may have therapeutic effects for partial corrections of the regressive structural changes associated with the aging process. - Link
Forty subjects with melasma were treated with C'ensil during an open-label trial over a period of 16 weeks. Each subject's skin pigmentation was assessed every 4 weeks using the Melasma Area and Severity Index (MASI and mexameter score. In addition, transepidermal water loss, skin dryness and irritation, and quality of life (Melasma Quality of Life Scale [MelasQoL] were evaluated.)) After 16 weeks, a significant decrease was noted in the degree of pigmentation based on the patients' MASI and mexameter scores.Link
Sixteen women with idiopathic melasma were included in our trial. After randomization by another clinician, they were instructed to use, at night, 5% ascorbic acid cream on one side of the face and 4% hydroquinone cream on the other side, for 16 weeks. The best subjective improvement was observed on the hydroquinone side with 93% good and excellent results, compared with 62.5% on the ascorbic acid side (P < 0.05; however, colorimetric measures showed no statistical differences. Side‐effects were present in 68.7% (11/16 with hydroquinone vs. 6.2% (1/16) with ascorbic acid.)) Although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; - Link
The study following performed on Indian subjects.
A split face, comparative study was conducted on 30 female melasma patients. After obtaining informed consent, microneedling with Tranexamic acid was done on the left side and microneedling with Vitamin C was done on the right side of the face. The improvement was evaluated on the basis of clinical photographs, MASI, Physician Global Assessment (PGA and Patient Global Assessment (PtGA at each visit (0, 4 and 8 weeks). At the end of 8 weeks, MASI, PGA and PtGA showed improvement with both tranexamic acid and vitamin C.)) The improvement was more with tranexamic acid than with vitamin C, although not statistically significant.Both TXA and Vitamin C are effective and safe treatments for melasma. -Link Link





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Note: SORRY FOR THE LONG POST ONCE AGAIN!!
During my research, I found some really interesting Insights & Dupes for popular vitamin C formulas and products from manufacturer documents. I also cost/formula analysed Most Popular Vitamin C products. I even looked up all possible options for vitamin C in Indian markets.
I will try to share these insights on my Instagram soon and maybe make a post about my finding and whatever is left out in a follow-up post if I am not being lazy. There is still a lot to explore about Vitamin C. Look out for my upcoming Instagram stories if you are curious.
Note: I do not consent to anyone sharing screenshots of my posts without my approval on any social platform.
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--Fun Fact--
The founder of SkinCeuticals Dr Sheldon R. Pinnell conducted turnkey research in the field on Vitamin C as a topical antioxidant. His first study published on topical application of vitamin C goes back to 1991. He filed his patent for Skinceutical CE ferulic in 2005. I guess that's why it remains the most coveted formulation and has been used by other researchers in various studies. It also justifies its price I guess. The good thing is that the patent is expiring in 2025! :P Till then we can only hope and pray someone invests time and research on developing more stable formulations and makes it available to consumers!
Murray, J.; Darr, D.; Reich, J.; Pinnell, S. Topical vitamin C treatment reduces ultraviolet B radiation-induced erythema in human skin. J. Investig. Dermatol. 1991, 96, 587.
Darr, D.; Combs, S.; Dunston, S.; Manning, T.; Pinnell, S.R. Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage. Br. J. Dermatol. 1992, 127, 24753.
Phillips, C.L.; Combs, S.B.; Pinnell, S.R. Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts. J. Investig. Dermatol. 1994.
Colven, R.M.; Pinnell, S.R. Topical vitamin C in ageing. Clin. Dermatol. 1996, 14, 227–234.
Pinnell, S.R.; Yang, H.; Omar, M.; Monteiro-Riviere, N.; DeBuys, H.V.; Walker, L.C.; Wang, Y.; Levine, M. Topical L-ascorbic acid: percutaneous absorption studies. Dermatol. Surg. 2001, 27, 137–142.
Darr D, Combs S, Dunston S, Manning T, Pinnell S. “UV photoprotection by combination topical antioxidants vitamin C and vitamin E”. J Am Acad Dermatol 2003; 48: 866-874.
Fu-Hsiung Lin 1, Jing-Yi Lin, Ravindra D Gupta, Joshua A Tournas, James A Burch, M Angelica Selim, Nancy A Monteiro-Riviere, James M Grichnik, Jan Zielinski, Sheldon R Pinnell **2**005 "Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin" Oct;125(4:826-32. DOI: 10.1111/j.0022-202X.2005.23768.x.)
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Are diets high in omega-6 polyunsaturated fatty acids unhealthy? (2001)

https://academic.oup.com/eurheartjsupp/article/3/suppl_D/D37/369529

Abstract

This article reviews the connection between dietary omega-6 fatty acids and atherosclerosis, carcinogenesis and insulin resistance. These polyunsaturated fatty acids (PUFAs) may be likened to ‘double-edged swords’: on one hand they are considered essential for membrane function and eicosanoid formation necessary for vascular, immune and inflammatory cell function, while on the other they lead to increased susceptibility to lipid oxidation, stimulating neoplastic cell growth in culture and impairing insulin activity. Omega-6 function should not be considered in isolation but as part of a complex of nutrient interactions together with omega-3 fatty acids (shared enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism — both within and between the fatty acid pathways. A high linoleate to arachidonate concentration occurs in insulin resistance, in diabetic complications and also in some tumours. Since the interaction between the omega-6 and omega-3 pathways in neither linear nor stochastic, specific dietary recommendations have to await clarification of these relationships. Adipose tissue fatty acid composition and function may be a suitable biomarker with which to study these questions. Current epidemiological and clinical evidence supports the regular consumption of cold-water fish as part of a balanced diet, in which attention to lifestyle and the quantities eaten (to prevent obesity and the insulin resistance syndrome) may be more critical than the nature of the fatty acids consumed.
Long url to the pdf
extract:

Atherosclerosis

Omega-6 PUFAs increase the susceptibility of lowdensity lipoprotein (LDL) to oxidative modifications[11,12] and, perhaps because of this, the risk for acute myocardial infarction and coronary thrombosis[13] . LA consumption may reduce the level of highdensity lipoprotein (HDL) cholesterol[14] , increasing the risk for coronary heart disease (CHD) mortality. Lipid peroxidation mediated by free radicals and/or hydroxy radicals is considered associated with the activation of radical scavengers, initiation and development of atherosclerosis[15] , although a better term would be atherothrombosis — to emphasize the additional roles of platelet and endothelial function in the pathological process.
submitted by Ricosss to ketoscience