Kelp

Ascophyllum nodosum (class of Phaeophyceae, order of Fucales) is a seaweed consumed in some diets, and subsequently is investigated for its role as a supplement due to being very high in phlorotannin compounds (up to 18%^[1]) relative to other seaweeds (with phlorotannin structures being unique to brown seaweed, and not existing in any terrestrial plant).^[2] Ascophyllum nodosum is characteristic of the mild intertidal zones of North Atlantic temperate rocky shores, and has been reported to grow along the coast of France and other european countries^[2][1] as well as Atlantic Canada.^[3]

Ascophyllum nodosum is sometimes referred to as Rockweed, although this generic term also may extend to the entire seaweed order of Fucales;^[4] this is opposing that of 'Kelp' which refers to the seaweed species of Laminariales.^[4]

Ascophyllum nodosum is a species of brown seaweed that is in the blanket term of Rockweed, and grows along many coasts

Ascophyllum nodosum contains the following Sulfated Polysaccharide chains (Fucoidans), which tend to have alternating (1→3) and (1→4) linkages,^[5][6] with both disulfated and trisulfated sugars (more of the former)^[7]:

• A particular sulfated polysaccharide (Fucoidan) known as Ascophyllan^[8] with a molecular size of 390kDa;^[9] Ascophyllan has 28.4% fucose, 19.4% sulfate, and 5.8% Uronic Acid in the carbohydrate fragment^[10]
• One particular Fucoidan (1.75% dry weight; 65.4% carbohydrate, 13.5% polyphenolic, and 18.5% protein) with the carbohydrate component comprising L-fucose (52.1%), glucose (21.3%), galactose (6.1%), and xylose (16.5%) at 420kDa^[11]
• A Fucoidan of 38.7% L-Fucose and 33.7% Sulfate by weight^[12]
• A 556kDa Fucoidan of 26.1% sulfate, 5.7% uronic acid, and 31.3% L-fucose^[13]
• 516kDaFucoidan of 35.8% L-Fucose, 18.4% Sulfate, and 11.6% Uronic Acid^[13]
• 600kDa Fucoidan of 43.2% L-Fucose, 35.3% Sulfate, and 1.7% Uronic Acid^[13]
• A 25kDa Fucoidan of 47%, 30% and 6% L-Fucose, Sulfate, and Uronic Acid respectively^[14]
• 18.6kDa Fucoidan of 39.7% L-Fucose, 27% Sulfate, and 4.1% Uronic Acid^[15]
• 45.4% L-Fucose, 22.1% Sulfate, and 9.9% Uronic Acid at 417kDa^[16]
• A large (1,323kDa) Fucoidan of 19.4% Sulfate, 28.4% L-fucose, and 5.8% Uronic Acid^[16]
• A small (13kDa) Fucoidan of 42% L-Fucose, 31% Sulfate, and 5% Uronic Acid;^[17] quite similar to a Fucoidan isolated by some other researchers (+/-1% Fucoidan, +/-3% Sulfate; same kDa) and possibly the same^[18][19]

Various Fucoidans (polysaccharides with a high sulfur content found in seaweeds exclusively), with only one of them being given a common name; Ascophyllan

With other components being:

• Myristic acid (3,027+/-395mcg/g dry weight), Palmitic acid (3,693+/-682mcg/g) and Stearic acid (240+/-79mcg/g) as saturated fats, collectively totalling less than 0.1% dry weight^[20]
• Monounsaturated fat Oleic Acid (23193+/-4833mcg/g; 2.3% dry weight) with another 18:1 monounsaturated fat (unknown position of double bond) at 120+/-42mcg/g^[20]
• Omega-6 fatty acids Linoleic acid (4884+/-236mcg/g), Gamma-Linoleic Acid (GLA; 235+/-42mcg/g) and Arachidonic Acid (4592+/-2986mcg/g) with no detectable Docosapentaenoic acid^[20]
• The fish oil fatty acid EPA (1569+/-127mcg/g; less than 0.01%) with no detectable DHA level^[20]
• The medium chain fatty acid Butyric acid^[21]
• Phlorotannins (5% dry weight^[22]) of moderate size relative to other species.^[23] Specific structures are not well characterized at this moment in time, and include just 1,2,3,5-tetrahydroxybenzene 2,5-disulfate ester^[24]
• Phenolics (2.5% of dry weight, increased with 50% methanolic extracts (15.37%), 100% methanolic (21.16%)^[25]) and may be concentrated with heat treatment (6.8mg/g dry weight at 80°C^[26])
• Quaternary Ammonium compounds such as betaine, choline,^[27] and laminine^[28] have been detected in the family previously
• Iodine at 553+/-186mcg/g dry weight^[29]
• Vanadium with seasonally related levels of 0.6-1.4mg/kg (summer to early winter) or 1.5-2.2mg/kg (winter to spring)^[30]
• Fucosterol, up to 50% of lipophilic components^[21]

Minerals and Fatty acids, with a respectable polyphenolic content (phloroglucinols and phlorotannins) that are not well characterized structurally

This species of seaweed might be used as a biomarker of heavy metal accumulation^[31] as it appears to be sensitive to uptake of surrounding minerals^[32] which appears to be somewhat related to the phenolics chelating minerals.^[33]

Similar components to many seaweeds, has a unique polysaccharide components called 'Ascophyllan' which may underlie novel effects of this seaweed relative to brown seaweed in general; may be an accumulator of heavy metals

When 4% Ascophyllum Nodosum is added to whole wheat bread (did not influence taste or acceptance of the meal) and compared against regular wheat bread, the consumption of this enriched bread at breakfast is associated with 16.4% reduced caloric intake at the subsequent meal in otherwise healthy adults who ate 100g of this bread product (4.6g Ascophyllum Nodosum) and appeared to reduce 24 hour energy intake by 506.1kcal.^[34] Self-reported sensation of fullness or satiety did not appear to be significantly altered.^[34]

One study reported reduced food intake independent of appetite; no mechanisms currently known

One study using ID-aIG™ (Ascophyllum nodosum with less than 5% Grape Seed Extract as carrier) noted in vitro lipase inhibitory potential of 71.0 +/-2.0% when incubated at 50mcg/mL, which was thought to precede the reduction in triglycerides by 30.6% of baseline values (control increased 49.9%) when rats were fed 400mg/kg of ID-aIG™ for 9 weeks in conjunction with a high fat diet (40mg/kg trending to significance but failing to reach); weight loss occurred, which may have confounded the results.^[35]

One study noting possible lipase inhibitory potential, which was fairly potent in vitro; no fecal analysis on lipids conducted, but possible inhibitory effects of fatty acid absorption

Fucoidans from Ascophyllan Nodosum possess anti-coagulant properties at 100mcg/mL (comparable to fucoidans from other seaweeds) but do not possess significant antithrombin activities.^[7]

May have anti-clotting properties; practical significance unknown

Incubation of Ascophyllum Nodosum extract (18% Phlorotannins) is able to rapidly activate SIRT1 to 165% of baseline within 20 minutes, and over 24 hours of incubation peak at 233% baseline levels.^[1] At both timepoints, this extract outperformed resveratrol at 100uM (120% and 165%, respectively).^[1]

Appears to be more potent in activating SIRT1 than resveratrol itself according to one study (SIRT1 being the protein thought to underlie resveratrol's longevity actions, which are still admittedly questionable)

Mechanistically, α-glucosidase is inhibited with a basic aqueous ethanolic extract of Ascophyllum Nodosum with an IC₅₀ of 77ug/mL; this extract had 22.5% phenolic content (attributed to phloroglucinols) and increasing the polyphenolic content to 70.2% improved the IC₅₀ to 24ug/mL.^[3] This appeared to precede a small but significant reduction in serum glucose following a maltose oral challenge when fed 300mg/kg bodyweight Ascophyllum Nodosum, and the polyphenolics appeared to reduce serum glucose following a sucrose challenge with 200mg/kg polyphenolic enriched fraction (weaker than the active control of arcabose at 25mg/kg).^[3] Another study investigating this enzyme (α-glucosidase) noted an IC₅₀ of 0.24ug/mL, and an IC₅₀ of 1.34ug/mL on α-amylase (the former comparable to Arcabose) with fresh, heat-treated Ascophyllum Nodosum at 80°C.^[26] One other study simply using 41mcg/mL Ascophyllum nodosum noted that α-amylase was inhibited up to 68.0 +/- 2.0, although a small Grape Seed Extract content was also present in this study.^[35]

The carbohydrate inhibitory potential is most likely related to the polyphenolic content, as the seasonal variation of polyphenolic compounds in this seaweed scale with seasonal changes in α-glucosidase inhibitory potential.^[36]

Consumption of 4.6g Ascophyllum Nodosum via a bread product does not appear to significantly reduce carbohydrate absorption in otherwise healthy humans.^[34] Another study using a blend of Ascophyllum nodosum and Fucus vesiculosus (Bladderwrack) at 500mg of the blend (InSea; standardized to greater) taken 30 minutes before a 50g test meal of bread failed to reduce glucose at any one time point but reduced glucose by 9% relative to control over 3 hours of measurement; a reduction in insulin (12.1%) and improved postprandial insulin sensitivity (7.9%) were also noted.^[37]

Appears to have fairly potent inhibitory action on carbohydrate absorption enzymes, particular those mediating starch absorption; there is some variance and one human study came back negative, and it is possible some of the currently uncharacterized phloroglucinols are potent inhibitors

A basic 50% aqueous ethanolic extract of Ascophyllum Nodosum is able to stimulate the rate of glucose uptake into adipocytes at 200mcg/mL (35.3%) and 400mcg/mL (138%); this was independent of insulin, and coincubation with insulin was not additive.^[3]

May aid glucose uptake into cells; preliminary evidence

A rat study using ID-aIG™ (brand name for Ascophyllum nodosum produced by Bioserae that uses using Grape Seed Extract as a carrier at less than 5% total weight; study conducted independently of Bioserae) at 40 or 400mg/kg for 9 weeks in rats given a high fat diet to induce weight gain noted that supplementation reduced the weight gain relative to control by 6.8% and 11.8% with the reductions in body fat reaching 9.8% and 19.0% respectively.^[35] The reasons for using GSE as carrier were not stated.

One study suggests possible anti-obese effects of a diet high in Ascophyllum nodosum, with the underlying mechanism not known

An extract of 0.05-0.2% Ascophyllum Nodosum extract (18% Phlorotannins) was able to attenuate the release of TNF-α at the lower concentrations with no effect on IL-6, but abolish the release of both cytokines at 0.2%.^[1] The fucoidans also possess general anti-inflammatory properties in response to LPS-induced macrophage stimulation, but in comparative analysis of the fucoidans from Ascophyllum nodosum against other sources these properties are not significantly better.^[7]

One study looking at anti-inflammatory actions of a basic extract noted potent anti-inflammatory properties, noted yet tested in a living system

Injections of the polysaccharide Ascophyllan at 50mg/kg for 4 days in mice was able to increase splenic Natural Killer (NK) cell activity towards YAC-1 cells from 2.5+/-0.53% to 12.3+/-0.36% (392% increase), which outperformed 50mg/kg Fucoidan (from bladderwrack).^[38]

The 50mg/kg injection of Ascophyllan was hypothesized to be about 50ug/mL concentration in serum assuming equal distribution.^[38] This concentration (50ug/mL) was then tested in macrophages ex vivo, where doses as low as 10ug/mL increased phagocytosis against YAC-1 cells (reducing YAC-1 viability to about 40%).^[38] Fucoidan also increased phagocytosis, but induced macrophage toxicity at higher doses while Ascophyllan did not up to 1000ug/mL.^[38] This preferable therapeutic threshold was noted elsewhere with isolated Ascophyllan relative to fucoidans form bladderwrack,^[8] and are active in concentrations as low as 3.1mcg/mL.^[8] This macrophage immunostimulatory actions was later found to have a bell-curve response, with 100mcg/mL being as potent as 0.1mcg/mL PMA and was secondary to stimulating NADPH oxidase and was not inhibited by the LPS inhibitor polymyxin B.^[9]

Ascophyllan, a particular Fucoidan, appears to be a potent immunostimulatory compound

The phlorotannins appear to be potent anti-oxidants, with fractions of Ascophyllum nodosum high in phlorotannins being comparable to Quercetin or Trolox on in vitro tests of anti-oxidative potential (ABTS+ and DPPH).^[22]

In Human epithelial cells, 0.1-0.2% Ascophyllum Nodosum extract (18% Phlorotannins) was able to significantly prevent a tBHP induced increase in oxidative damage from 51% to 14%; this was not observed with 0.5%, which was similar to tBHP control.^[1]

Appears to have anti-oxidant effects at low concentrations, although the lack of effect at 0.5% suggests it may be either inert or pro-oxidative at higher doses (commonly seen with direct antioxidants that may also donate electrons, rather than merely sequester them)

In intestinal cells, it seems that Ascophyllum nodosum can protect the H₂O₂ induced reduction of the superoxide dismutase (SOD) enzyme^[39] but elsewhere has failed to preserve SOD in response to tert-butyl hydroperoxide induced reductions (despite other seaweeds doing so).^[40]

A study in rats using up to 15% Ascophyllan nodosum in the diet failed to find significant toxicological signs, but noted a change in urinary parameters (specifically, the TCA intermediates citrate, 2-oxoglutarate, succinate, trimethylamine (TMA), TMA-N-oxide, and malonate increased while urinary taurine, creatinine, and acetate decreased).^[41] The increased urinary levels of TMA were thought to possibly be related to the betaine and choline content of the seaweed.^[41]

Currently no toxicity noted with Ascophyllum nodosum supplementation