Ascophyllum nodosum

Ascophyllum nodosum is a species of seaweed found around the globe. It is one of the many species of seaweed called kelp.

Ascophyllum nodosum contains compounds called phlorotannins, which are unique to seaweed and may be able to inhibit starch and lipid absorption. This effect is very unreliable, to the point where two human studies investigating carbohydrate absorption reported two opposite effects.

Ascophyllum nodosum also contains a compound called ascophyllan, which may have immunostimulatory properties. Ascophyllum nodosum extract has anti-inflammatory properties. Much more research is needed to determine the practical significance of Ascophyllum nodosum supplementation.

Though Ascophyllum nodosum is a healthy food, there is no evidence to support its usefulness as a supplement.

Human studies investigating Ascophyllum nodosum use 4,600 mg of Ascophyllum nodosum extract added to a food product, taken once per day.

More research is needed to determine if this is the optimal dose of Ascophyllum nodosum. Different extract concentrates have not been tested.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects ascophyllum nodosum has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	Robust research conducted with repeated double-blind clinical trials
	Multiple studies where at least two are double-blind and placebo controlled
	Single double-blind study or multiple cohort studies
	Uncontrolled or observational studies only

Level of Evidence ? The amount of high quality evidence. The more evidence, the more we can trust the results.	Outcome	Magnitude of effect ? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.	Consistency of research results ? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.	Notes
	Food Intake	Minor	- See study	The reduction in voluntary food intake noted was 16.4% of a test meal (which was 80kcal in this study) and is not likely to make significant effects during weight loss.
	Appetite	-	- See study	The noted reduction in food intake was not associated with decreased appetite.

1.1Sources

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

1.2Composition

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

2.1Appetite

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

3.1Absorption

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

3.2Blood clotting

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

4.1Mechanisms

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)

5.1Absorption

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

5.2Mechanisms

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

6.1Interventions

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

7.1Macrophages

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

7.2Immunostimulation

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

8.1General

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]

9.1General

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

1. ^ a b c d e f Dutot M, et al. Antioxidant, anti-inflammatory, and anti-senescence activities of a phlorotannin-rich natural extract from brown seaweed Ascophyllum nodosum. Appl Biochem Biotechnol. (2012)
2. ^ a b Interspecific and temporal variation in phlorotannin levels in an assemblage of brown algae.
3. ^ a b c d Zhang J, et al. Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum. Can J Physiol Pharmacol. (2007)
4. ^ a b Seeley RH, Schlesinger WH. Sustainable seaweed cutting? The rockweed (Ascophyllum nodosum) industry of Maine and the Maritime Provinces. Ann N Y Acad Sci. (2012)
5. ^ Chevolot L, et al. A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae. Carbohydr Res. (2001)
6. ^ Chevolot L, et al. Further data on the structure of brown seaweed fucans: relationships with anticoagulant activity. Carbohydr Res. (1999)
7. ^ a b c Cumashi A, et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. (2007)
8. ^ a b c Jiang Z, et al. The potent activity of sulfated polysaccharide, ascophyllan, isolated from Ascophyllum nodosum to induce nitric oxide and cytokine production from mouse macrophage RAW264.7 cells: Comparison between ascophyllan and fucoidan. Nitric Oxide. (2011)
9. ^ a b Wang Y, et al. Stimulatory effect of the sulfated polysaccharide ascophyllan on the respiratory burst in RAW264.7 macrophages. Int J Biol Macromol. (2013)
10. ^ Nakayasu S, et al. Biological activities of fucose-containing polysaccharide ascophyllan isolated from the brown alga Ascophyllum nodosum. Biosci Biotechnol Biochem. (2009)
11. ^ Foley SA, et al. An unfractionated fucoidan from Ascophyllum nodosum: extraction, characterization, and apoptotic effects in vitro. J Nat Prod. (2011)
12. ^ Polyanionic characteristics of purified sulphated homofucans from brown algae.
13. ^ a b c Nardella A, et al. Anticoagulant low molecular weight fucans produced by radical process and ion exchange chromatography of high molecular weight fucans extracted from the brown seaweed Ascophyllum nodosum. Carbohydr Res. (1996)
14. ^ Degradation of algal (Ascophyllum nodosum) fucoidan by an enzymatic activity contained in digestive glands of the marine mollusc Pecten maximus.
15. ^ Haroun-Bouhedja F, et al. Relationship between sulfate groups and biological activities of fucans. Thromb Res. (2000)
16. ^ a b Characterization of polysaccharides extracted from brown seaweeds.
17. ^ Berteau O, et al. Characterization of a new alpha-L-fucosidase isolated from the marine mollusk Pecten maximus that catalyzes the hydrolysis of alpha-L-fucose from algal fucoidan (Ascophyllum nodosum). Glycobiology. (2002)
18. ^ Daniel R, et al. Electrospray ionization mass spectrometry of oligosaccharides derived from fucoidan of Ascophyllum nodosum. Carbohydr Res. (2007)
19. ^ Daniel R, et al. Regioselective desulfation of sulfated L-fucopyranoside by a new sulfoesterase from the marine mollusk Pecten maximus: application to the structural study of algal fucoidan (Ascophyllum nodosum). Eur J Biochem. (2001)
20. ^ a b c d van Ginneken VJ, et al. Polyunsaturated fatty acids in various macroalgal species from North Atlantic and tropical seas. Lipids Health Dis. (2011)
21. ^ a b Rayirath P, et al. Lipophilic components of the brown seaweed, Ascophyllum nodosum, enhance freezing tolerance in Arabidopsis thaliana. Planta. (2009)
22. ^ a b Blanc N, et al. Radical-scavenging capacity of phenol fractions in the brown seaweed Ascophyllum nodosum: an electrochemical approach. Talanta. (2011)
23. ^ Steevensz AJ, et al. Profiling phlorotannins in brown macroalgae by liquid chromatography-high resolution mass spectrometry. Phytochem Anal. (2012)
24. ^ 1,2,3,5 tetrahydroxybenzene 2,5 disulfate ester: the "phenolic precursor" in gelbstoff forming exudates from the marine brown alga Ascophyllum nodosum (L.) Lejol.
25. ^ Audibert L, et al. Phenolic compounds in the brown seaweed Ascophyllum nodosum: distribution and radical-scavenging activities. Phytochem Anal. (2010)
26. ^ a b Apostolidis E, Lee CM. In vitro potential of Ascophyllum nodosum phenolic antioxidant-mediated alpha-glucosidase and alpha-amylase inhibition. J Food Sci. (2010)
27. ^ DaSilva E, Jensen A. Benthic marine and blue-green algal species as a source of choline. J Sci Food Agric. (1973)
28. ^ Quaternary ammonium compounds in species of the Fucaceae (Phaeophyceae) from Britain.
29. ^ Kundel M, et al. Application of mass spectrometric techniques for the trace analysis of short-lived iodine-containing volatiles emitted by seaweed. Anal Bioanal Chem. (2012)
30. ^ Hartung J, et al. Bromoperoxidase activity and vanadium level of the brown alga Ascophyllum nodosum. Phytochemistry. (2008)
31. ^ Morrison L, Baumann HA, Stengel DB. An assessment of metal contamination along the Irish coast using the seaweed Ascophyllum nodosum (Fucales, Phaeophyceae). Environ Pollut. (2008)
32. ^ Stengel DB, Dring MJ. Copper and iron concentrations in Ascophyllum nodosum (Fucales, Phaeophyta) from different sites in Ireland and after culture experiments in relation to thallus age and epiphytism. J Exp Mar Bio Ecol. (2000)
33. ^ Studies on phenol content and heavy metal uptake in fucoids.
34. ^ a b c Hall AC, et al. Ascophyllum nodosum enriched bread reduces subsequent energy intake with no effect on post-prandial glucose and cholesterol in healthy, overweight males. A pilot study. Appetite. (2012)
35. ^ a b c Terpend K, et al. Effects of ID-alG™ on weight management and body fat mass in high-fat-fed rats. Phytother Res. (2012)
36. ^ Apostolidis E, et al. Seasonal variation of phenolic antioxidant-mediated α-glucosidase inhibition of Ascophyllum nodosum. Plant Foods Hum Nutr. (2011)
37. ^ Paradis ME, Couture P, Lamarche B. A randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women. Appl Physiol Nutr Metab. (2011)
38. ^ a b c d Nakano K, et al. Immunostimulatory activities of the sulfated polysaccharide ascophyllan from Ascophyllum nodosum in in vivo and in vitro systems. Biosci Biotechnol Biochem. (2012)
39. ^ In vitro and cellular antioxidant activities of seaweed extracts prepared from five brown seaweeds harvested in spring from the west coast of Ireland.
40. ^ O'Sullivan AM, et al. Assessment of the ability of seaweed extracts to protect against hydrogen peroxide and tert-butyl hydroperoxide induced cellular damage in Caco-2 cells. Food Chem. (2012)
41. ^ a b Simmons-Boyce JL, et al. Dietary Ascophyllum nodosum increases urinary excretion of tricarboxylic acid cycle intermediates in male Sprague-dawley rats. J Nutr. (2009)