What is bladderwrack

Bladderwrack also known as kelp or seaweed Fucus vesiculosus (or other Fucus species, and Ascophyllum nodosum), bladder fucus, black-tang, blasentang, cut-weed, sea-wrack, seetang, fucus, kelpware or quercus marina, consists of the dried brown seaweed whole plant. Bladderwrack contains soluble fiber (e.g., alginic acid), vitamin B12, iron and iodine. Bladderwrack (Fucus vesiculosus) can also contain heavy metals (e.g., arsenic, cadmium, lead). Bladderwrack is a source of iodine and it is this iodine that provides the theoretical basis for bladderwrack’s activity. Bladderwrack’s average iodine content is 504 μg/g (approx) ¹. However it should be noted that the iodine content is variable in Bladderwrack seaweeds ². This variability as well as the daily intake of iodine make predictions difficult. The World Health Organization (WHO) advises a daily iodine intake of 100 to 150 μg. Some countries or organizations advise daily iodine intake levels up to 200-300 μg. The World Health Organization (WHO), United Nations Children’s Fund (UNICEF), and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) recommend a slightly higher iodine intake for pregnant women of 250 mcg per day ³. During pregnancy and lactation there is an increased urinary loss of iodine caused by a higher renal blood flow. Therefore a higher daily iodine intake is advised (up to 230 μg) ⁴. According to some sources doses exceeding 150 μg iodine per day may cause the side effects of increased thyroid gland function such as heart palpitation, increased heart rate, trembling, changes in blood pressure and increased basal metabolism, though rarely reported. High iodine intake can also cause aggravation of acne. It has even been mentioned that iodine in Bladderwrack (Fucus vesiculosus) can cause a thyrotoxic crisis (thyroid storm) and hypersensitivity reactions ⁵. Therefore long-term use in subjects with normal thyroid function should be avoided. A generalized allergic reaction can occur ⁶. Some sources are warning against latent hyperthyroidism if Bladderwrack extracts are administered for a long time ⁷.

If iodine levels in bladderwrack are sufficiently high to cause weight loss, however, they would also be high enough to cause an overactive thyroid condition (hyperthyroidism). People use Bladderwrack (Fucus vesiculosus) for conditions such as thyroid disorders, iodine deficiency, obesity, weight loss and many others, but there is no good scientific evidence to support these uses. Using Bladderwrack (Fucus vesiculosus) can also be unsafe. Bladderwrack (Fucus vesiculosus) contains significant amounts of iodine, which might make hyperthyroidism and hypothyroidism worse.

In the 16th century, Bladderwrack (Fucus vesiculosus) was used in China to treat goitre (goiter or enlarged thyroid gland) caused by iodine deficit. In the 17th century, Bladderwrack (Fucus vesiculosus) was used in France to treat goitre and other thyroid complaints. This was also the case for the United Kingdom with the additional indication of obesity treatment. In the United States, Bladderwrack (Fucus vesiculosus) was also indicated for psoriasis and as a strengthening agent. During the 18th century, Bladderwrack (Fucus vesiculosus) was used to treat asthma, goiter (enlarged thyroid) and skin diseases ⁸. Other applications were treatment of rheumatism and slimming baths, but the latter is questionable ⁹.

Bladderwrack (Fucus vesiculosus) grows in different environmental conditions from saline lagoons to rocky shores and it is widespread along the coastlines worldwide, mostly at North American and Western European shores of the North Atlantic and the Pacific Ocean ¹⁰. Its chemical composition depends on the harvest season, geographic location, and environmental factor such as substrate firmness, exposure to ice and waves, salinity, wave force, light, or competition between macroalgae ¹¹. However, it is essentially constituted by polyphenolic compounds, proteins, minerals, iodine, vitamins, fatty acids, and non-digestible polysaccharides ¹².

Table 1. Recommended Dietary Allowances (RDAs) for Iodine

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months	110 mcg*	110 mcg*
7–12 months	130 mcg*	130 mcg*
1–3 years	90 mcg	90 mcg
4–8 years	90 mcg	90 mcg
9–13 years	120 mcg	120 mcg
14–18 years	150 mcg	150 mcg	220 mcg	290 mcg
19+ years	150 mcg	150 mcg	220 mcg	290 mcg

Footnote: * Adequate Intake (AI) is the intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an Recommended Dietary Allowance (RDA). Recommended Dietary Allowance (RDA) is the average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.

[Source ¹³ ]

Table 2. Tolerable Upper Intake Levels (ULs) for Iodine

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months	Not possible to establish*	Not possible to establish*
7–12 months	Not possible to establish*	Not possible to establish*
1–3 years	200 mcg	200 mcg
4–8 years	300 mcg	300 mcg
9–13 years	600 mcg	600 mcg
14–18 years	900 mcg	900 mcg	900 mcg	900 mcg
19+ years	1,100 mcg	1,100 mcg	1,100 mcg	1,100 mcg

Footnote: * Formula and food should be the only sources of iodine for infants.

[Source ¹³ ]

Bladderwrack health benefits

Nowadays Bladderwrack (Fucus vesiculosus) administered orally and topically. In traditional medicine Bladderwrack (Fucus vesiculosus) is administered orally for different conditions such as weight loss, treatment of gastritis, pyrosis, reflux esophagitis and hiatus hernia, prevention of atherosclerosis, viscous blood and hypercholesterolemia, mineral deficit, management of constipation, colitis, asthenia, fatigue, mineral deficit, anemia, hair loss and leg cramps, an adjuvant for menopausal complaints, fibrocystic breasts, prostate complaints, growth deprivation,, arthritis, arthrosis, gout and lymph edema ¹⁴. Traditionally Bladderwrack is also administered topically for the treatment of wounds, an adjuvant in the therapy for cellulites and obesity and an aid for rheumatism and arthritis ¹⁵, ¹⁶. In cosmetics, Bladderwrack (Fucus vesiculosus) is applied because of its iodine and oligoelement content ¹⁶. Ulbricht et al. ¹⁷ made an overview of experimental and traditional use of Bladderwrack (Fucus vesiculosus) monotherapy or in combination. Among the pathological conditions wherein the use of Bladderwrack seaweed or its components is reported are: acne, enhanced blood clotting tendency, atopic dermatitis, breast diseases (mastalgia, menopausal syndrome, dysmenorrhea, fibroadenomatosis), burns, hyperglycemia and overweight. Most of the information on humans is unclear or of conflicting scientific evidence. Bladderwrack is used as a natural source of iodine. The iodine content gives some plausibility to a possible stimulating effect on the thyroid gland. There is the connotation of an increased burning of fat ¹⁸.

However, there is insufficient evidence to rate effectiveness Bladderwrack (Fucus vesiculosus) for:

• Obesity or weight loss. Early research suggests that taking Bladderwrack (Fucus vesiculosus) along with lecithin and vitamins doesn’t help people lose weight.
• Prediabetes.
• Achy joints (rheumatism).
• Arthritis.
• “Blood cleansing”.
• Constipation.
• Digestive problems.
• “Hardening of the arteries” (arteriosclerosis).
• Iodine deficiency.
• Thyroid problems, including an over-sized thyroid gland (goiter).
• Other conditions.

It has been demonstrated that the intake of iodine-containing Bladderwrack (Fucus vesiculosus) preparations can influence thyroid function. The maximum content of iodine is 0.2%, according to the monograph in the European Pharmacopoeia ¹⁴. The amount of iodine by intake of Bladderwrack (Fucus vesiculosus) adds to the daily intake from food. Therefore a maximum intake is defined to guarantee a safe use as the regular intake enhanced with the iodine from Bladderwrack. The resulting intake of total iodine should not exceed the upper limit of 600 μg ¹⁴. A maximum daily limit of 400 μg iodine intake by Bladderwrack (Fucus vesiculosus) was defined in the European Pharmacopoeia monograph. In the US the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board together with Health Canada are pursuing a joint project which proposes a tolerable upper level of intake for iodine for adults of 1,100 μg/day. WHO has suggested a provisional maximum tolerable daily intake of 1,100 μg/day from all sources, equivalent to 17 μg/kg body weight. In countries with long-standing iodine deficiency disease the intake should not exceed 500 μg/day to avoid the occurrence of hyperthyroidism. In France, the Expert Committee on Human Nutrition has suggested an upper limit of 500 μg iodine/day in countries with long-standing iodine deficiency disease to avoid the occurrence of hyperthyroidism.

Bladderwrack for weight loss

Despite there being insufficient evidence that Bladderwrack (Fucus vesiculosus) help users lose weight, on the basis of its long-standing ‘traditional use’, bladderwrack preparation can be used in addition to a low-calorie diet to help overweight adults lose weight, after other serious conditions have been excluded by your doctor. This means that, although there is insufficient evidence from clinical trials, the effectiveness of Bladderwrack (Fucus vesiculosus) herbal medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years. Bladderwrack medicines should only be used in adults. If no weight loss is achieved after 10 weeks of taking Bladderwrack a doctor or qualified healthcare practitioner should be consulted. Detailed instructions on how to take bladderwrack medicines and who can use them can be found in the package leaflet that comes with the medicine.

Bladderwrack for prediabetes and diabetes

The study by Roy et al. ¹⁹ showed that the administration of phlorotannins from Bladderwrack (Fucus vesiculosus) had low IC50 values and high maximum inhibition rates of alpha-amylase and alpha-glucosidase in test tube study. Low IC50 value means that the drug is effective at low concentrations. This demonstrated that phlorotannins from Bladderwrack may be potent inhibitors of both α-amylase and α-glucosidase in test tube study. Because α-amylase and α-glucosidase are of great importance in the breakdown of carbohydrates, the authors concluded that phlorotannins might be useful in modulating plasma glucose and insulin levels after a meal if phlorotannins also showed these effects animal studies. This could be a plausible hypothesis for a mechanism of action to justify using Bladderwrack (Fucus vesiculosus) in clinical studies with prediabetic patients.

In that same study performed by Roy et al. ¹⁹ it was shown that the administration of phlorotannins from Bladderwrack (Fucus vesiculosus) by gavage significantly decreased the raise in the blood glucose after a meal compared to control. This could, at least partly, be due to the extended absorption caused by phlorotannins, which was observed in this study. Furthermore phlorotannins from Bladderwrack also decreased the peak increase in insulin and the area under the curve for insulin, but these effects were not significant. In order to evaluate the therapeutic consequences, more clinical experience is needed. In a study carried out by Lamela et al. ²⁰ showed that Bladderwrack extracts did not have any significant effect on blood glucose levels.

The results of the study by Roy et al. ¹⁹ were promising, but they are not concordant with the results of the study by Lamela et al. ²⁰, so the effect of Bladderwrack on serum glucose levels needs further investigation.

Bladderwrack for skin health

Bladderwrack has been used as a topical treatment for skin issues, such as cellulite, skin aging, and burns. Early research has shown that the antioxidants in bladderwrack, namely fucoidan, promote collagen synthesis in the skin, which may help improve the look of cellulite, increase skin healing, and delay premature skin aging. The results of a study by Thring et al. ²¹ showed an anti-collagenase activity by Bladderwrack (Fucus vesiculosus). Its anti-elastase activity was mild and it had slightly anti-oxidative properties. These effects could be useful, but it is not known whether Bladderwrack extracts are able to penetrate in sufficiently high concentrations through the skin. As a consequence, the clinical relevance of this study is limited.

In a study by Fujimara et al. ²², the results of the experiment showed that the high polar fraction and fucoidan from Bladderwrack (Fucus vesiculosus) significantly stimulated gel contraction and increased the integrin α2β1 expression on fibroblasts compared to control. The authors suggested that the increase in gel contraction arises from an increased integrin α2β1 expression and that the high polar fraction of Bladderwrack (Fucus vesiculosus) contains fucoidan. It needs to be noted that the exact chemical structure of the active fucoidan remains unknown. A drawback of this study is that a test tube model of dermal tissue was used. The consequence is that it is unknown to what extent Bladderwrack extracts penetrate the epidermis and reach the dermis in clinical conditions. This limits the clinical relevance of the study.

In the first phase of a two-phase study, applying bladderwrack extract to skin samples led to a 228% increase in collagen production, compared with no improvements in the control group ²³.

In the second phase, a mixture of bladderwrack extract and other algae extracts was tested on human upper leg skin for 12 weeks. Compared with the placebo product, the algae mixture led to a significant decrease in cellulite appearance and fat thickness ²³.

Other older studies using topical gels containing 1% bladderwrack extract were associated with an increase in collagen production ²⁴.

Also, bladderwrack’s high antioxidant content has been linked to less collagen and elastin breakdown when applied to human skin samples. Preventing the breakdown of collagen and elastin is important for the appearance of youthful skin ²⁵.

Despite these results, long-term human studies are lacking. What’s more, no research supports consuming bladderwrack as a food or supplement to promote skin health.

Bladderwrack antioxidant activity

The article by Rupérez et al. ²⁶ showed that the antioxidant capacity from Bladderwrack (Fucus vesiculosus) might be attributed to fucans and not only to the polyphenols. The article by Diaz-Rubio et al. ²⁷ suggested that polyphenols play the key role in the antioxidant capacity. Anyhow, these two articles suggested that Bladderwrack might be used as a source of natural antioxidants.

In a study by O’Sullivan et al. ²⁸ showed that Bladderwrack extracts displayed all three measures of protection against free radicals activities (the ferric reducing antioxidant activity, radical scavenging activity and the prevention of beta-carotene bleaching). Both catalase and superoxide dismutase are important enzymes in neutralizing free radicals. In this experiment the activity of neither catalase nor superoxide dismutase increased significantly. Reduced glutathione (GSH and consists of glutamine, cysteine and glycine) has a key role in non-enzymatic antioxidant activity. This study showed that the levels of glutathione (GSH) in cells treated with Bladderwrack extracts increased significantly. Hydrogen peroxide (H2O2) causes DNA damage in cells. This study showed that in cells treated with Bladderwrack extract the H2O2-induced DNA damage decreased significantly. The overall conclusion of all the experiments conducted by O’Sullivan et al. ²⁸ was that Bladderwrack extracts showed significant antioxidant activity in vitro (test tubes). However, it needs to be noted that the antioxidant activity of Bladderwrack extracts is much lower than the one of ascorbic acid (vitamin C).

The study performed by Parys et al. ²⁹ did not mention if a statistical analysis had been carried out to determine whether the results were statistically significant. The study compared the radical scavenging activity of phloroglucinol, which is known to scavenge radicals, to three fucophlorethols isolated from Bladderwrack. All analyzed fucophlorethols showed radical scavenging activity comparable to that of phloroglucinol.

These experiments are typical for screening purposes. Bladderwrack (Fucus vesiculosus) seems to have antioxidative properties in vitro (in test tube studies), but the activity is lower than the one of ascorbic acid. The therapeutic consequences are not clear and should be clinically investigated.

Bladderwrack anti-inflammatory effect

In a study carried out by Trento et al. ³⁰ showed that fucansulfate from Bladderwrack significantly decreased the number of polymorphonuclear lymphocytes that adhere to the rabbit aorta. This decrease suggested that fucan sulfate from Bladderwrack had an anti-inflammatory effect by interacting with thrombin. It is not clear what may be the clinical relevance of this finding in vivo.

Bladderwrack effects on estrogen and progesterone levels

Experiments performed by Skibola et al. ³¹ showed that 50 and 75 μmol/l Bladderwrack (Fucus vesiculosus) dose-significantly reduced 17β-estradiol levels in human granulosa cells. The observed inhibition was concentration-dependent. These results suggested that Fucus vesiculosuseither inhibited 17β-estradiol production or stimulated its breakdown. The inhibition of progesterone production was less prominent, and appearantly there was no concentration-response relationship. On the other hand, there was a clearcut concentration-dependent occupancy of the estrogen and progesterone receptors.

The results suggested that certain components of Bladderwrack (Fucus vesiculosus) compete with estradiol and progesterone for binding to their receptors and that there are components in Bladderwrack (Fucus vesiculosus) that are antagonists of estradiol and progesterone. In the test tube study by Parys et al. ²⁹, the IC50 values of fucophlorethols from Bladderwrack for the enzyme aromatase showed that these fucophlorethols inhibited aromatase. Aromatase turns androgens into estrogens and estrogens play a key role in estrogen-dependent cancers. The IC50 value is that concentration of a drug that reduces the activity (or binding) of another drug to an enzyme by 50%. Under certain conditions it can used to express the affinity of the enzyme inhibitor. These in vitro results suggested according to the authors that fucophlorethols from Bladderwrack might be used in the prevention and/or treatment of estrogen-dependent cancers. However, this needs further investigation, because this effect may arise from unspecific interaction of fucophlorethols with aromatase and it is unclear whether the effect would also be present in vivo (animal or human studies).

The overall conclusion of both studies is that the activity of Bladderwrack (Fucus vesiculosus) on estrogen and progestagen receptors and production needs to be further clarified non-clinically as well as clinically.

Bladderwrack anticoagulant effects

The study by Trento et al. ³⁰ showed that fucansulfate in vitro significantly decreased the platelet aggregation induced by thrombin and dose-dependently inhibited the production of thrombin compared to control. In a study performed by de Azevedo et al. ³² to tests the activated partial thromboplastin time (aPTT) and the prothrombin time (PT), which are both measures for coagulation, in the presence of Bladderwrack extracts. The results showed that Bladderwrack extracts significantly prolonged both the activated partial thromboplastin and prothrombin time compared to control. However in both experiments this prolongation was much lower than that caused by low molecular weight heparins.

A study carried out by Kwak et al. ³³ showed that fucoidan from Bladderwrack (Fucus vesiculosus) inhibited ADP-induced aggregation of platelets. This inhibition increased with increasing concentrations of fucoidan and was approximately 2 times stronger than that of heparin. The study also showed that fucoidan from Bladderwrack (Fucus vesiculosus) inhibited the activities of both thrombin and factor Xa. These inhibitions increased concentration-dependently, but was much lower than that of heparin. The experiments carried out by Kwak et al. ³³ showed that fucoidan from Bladderwrack prolonged the activated partial thromboplastin time, but this effect was smaller than that of heparin. The conclusion of this study was that fucoidan from Bladderwrack had less potent antithrombotic activities than heparin in vitro. For instance in inhibiting thrombin and factor Xa activities and prolongating the activated partial thromboplastin time, it scored less than heparin. The only experiment in which fucoidan scored better than heparin was in the inhibition of ADP -induced platelet aggregation.

In a study carried out by Dürig et al. ³⁴ was designed to test the impact of the molecular weight and sulfate content of fucoidan from Bladderwrack (Fucus vesiculosus) on the anticoagulant activity of fucoidan. The conclusion of the platelet aggregation assay was that if the sulfate level remained constant and the molecular weight increased, the high molecular weight fucoidan from Bladderwrack increased platelet aggregation significantly more than low molecular weight fucoidan. The experiment in which the activated partial thromboplastin time, α2-antiplasmin activity and plasminogen activator inhibitor activity were measured showed that if the molecular weight of the fucoidan remained constant and the sulfate level increased, then the anticoagulant effects increased, whereas the α2-antiplasmin inhibitor activity and plasminogen activator inhibitor activities decreased.

In contrast with the other studies on the anticoagulant activity of fucoidan from Bladderwrack (Fucus vesiculosus) in vitro, the study by Dürig et al. ³⁴ concluded that fucoidan could also stimulate coagulation. However, Kwak et al. ³³ reported that fucoidan with low molecular weight only slightly stimulated coagulation and even has anticoagulant activities; which is consistent with the other studies described above.

In the study performed by Cumashi et al. ³⁵ showed that the anticoagulant activity of 1 mg fucoidan from Bladderwrack (Fucus vesiculosus) was equal to that of approximately 9.4 U heparin and that fucoidan from Bladderwrack (Fucus vesiculosus) did not inhibit the platelet aggregation induced by thrombin significantly.

Most of the experiments were done with human plasma or platelets (only once with rabbit platelets). The anticoagulant activity was compared amongst others with heparin. The antithrombotic activity of fucoidan from Bladderwrack seems to be comparable with heparin (high and low molecular weight) in the experimental models used. The question remains whether in clinical conditions improvements of hard endpoints will be obtained.

Bladderwrack inhibition of reverse transcriptase activity of HIV

The study carried out by by Quieroz et al. ³⁶ showed that galactofucan, fucoidan and fucan B from Bladderwrack (Fucus vesiculosus) inhibited reverse transcriptase concentration dependently. Fucoidan had the strongest inhibiting acitivity of reverse transcriptase: 0.5 μg/ml fucoidan inhibited reverse transcriptase for activated DNA by 84.0 ± 4.3% and for synthetic polynucleotides by 98.1 ± 4.5%. As no positive controls were used, it is difficult to estimate the value of the experiments.

Bladderwrack effects on the immune system

A study carried out by Oomizu et al. ³⁷ showed that fucoidan from Bladderwrack significantly inhibited the release of IgE by B cells in vitro. However, only one, rather high concentration was used, without any concentration-effect relationship. The relevance of the results is limited.

A study carried out by Price et al. ³⁸ showed that Bladderwrack extracts inhibited histamine release from mast cells in vitro by approximately 58%. Again, no concentration dependence was investigated, which reduces the importance of the observations.

In a study by Choi et al. ³⁹ showed that when macrophages and lymphocytes were exposed to fucoidan from Bladderwrack, the viability ofmacrophages and lymphocytes increased significantly in vitro.

In a study by Kim and Joo ⁴⁰ showed that fucoidan from Bladderwrack increased the viability of dendritic cells significantly. The production of interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) by fucoidan treated dendritic cells also was significantly higher, whereas the antigen uptake was significantly lower. TNF-α and IL-12 play important roles in the protection against pathogens. The significantly increased expression of MHC class I and II, CD54 and CD86 on leukocytes suggested that fucoidan had immunostimulatory effects and stimulated the maturation of dendritic cells. However the concentrations to obtain the effect were too high to create persepectives in vivo.

As an overall conclusion on the effect of fucoidan and other extracts from Bladderwrack on the immune system, it can be stated that the consequences are limited to experimental conditions.

Bladderwrack in atherosclerosis and restenosis prevention

A study performed by Kwak et al. ³³ showed that fucoidan from Bladderwrack (Fucus vesiculosus) decreased the production of several inflammatory cytokines by human umbilical endothelial cells in vitro. This suggested that fucoidan from Bladderwrack had a qualitative potential in the prevention of atherosclerosis and restenosis, because in both processes inflammation plays a role. This study also showed that fucoidan from Bladderwrack inhibited the proliferation, migration and adhesion of rat aortic smooth muscle cells in vitro more than heparin. However it should be noted that high concentrations were used which may be difficult to obtain in vivo.

Bladderwrack anticancer effects

Several studies about the induction of apoptosis in tumor cell lines have been performed. Most of them concern fucoidan from Bladderwrack and one extract of Bladderwrack. The study performed by Aisa et al. ⁴¹ mentioned that there was a significant difference in growth between the control group and the group treated with 100 μg/ml fucoidan from Bladderwrack (Fucus vesiculosus). Therefore, it is difficult to draw conclusions from this article. The in vitro study found that human lymphoma cells treated with fucoidan from Bladderwrack (Fucus vesiculosus) proliferated less compared to the control group. This study also found that the cells treated with fucoidan from Bladderwrack (Fucus vesiculosus) expressed more caspase-3 and less Rh123, GSK and ERK compared to control in vitro. The authors assumed that this changed expression was correlated with the increased apoptosis level of the cells.

In the study carried out by Hyun et al. ⁴² showed that concentrations of 10, 30, 50 and 100 μg/ml fucoidan from Bladderwrack inhibited human colon carcinoma cell proliferation significantly. The experiments also suggested that there was a correlation between downregulation of Bcl-2, increasing concentrations of Bax and active ERK, p38 kinase, caspase-3, caspase-9 and the inhibition of the proliferation of the cancer cells all caused by fucoidan from Bladderwrack. The conclusion of this study was that fucoidan from Bladderwrack significantly induced apoptosis in colon carcinoma cells in vitro.

In another study by Ale et al. ⁴³ that was designed to examine the effects of fucoidan from Bladderwrack on melanoma B16 cells. The results showed that fucoidan significantly reduced the viability of melanoma B16 cells and according to the results this effect was, at least partly, achieved by a significant increase of apoptosis and caspase-3 activity. The conclusion of this study was that fucoidan from Bladderwrack significantly inhibited growth and induced apoptosis in melanoma B16 cells in vitro.

In another study carried out by Choi et al. ³⁹, showed that addition of a combination of fucoidan from Bladderwrack (Fucus vesiculosus) and macrophages or lymphocytes to YAC1 or B16 tumor cells caused significant higher tumor cell death compared to control. The study also showed that compared to control the activity of myeloperoxidase and lysosomal phosphatase increased significantly in macrophages treated with fucoidan. Both enzymes are produced by macrophages and play a role in phagocytosis. Furthermore fucoidan-treated macrophages produced significantly higher amounts of TNF-α, IL-6, nitrite and H2O2. Nitrite is an indicator of nitric oxide (NO) production and NO and H2O2 are molecules which have cytotoxic effects. Both TNF-α and IL-6 play important roles in immunomodulation. The conclusion of this study was that addition of fucoidan from Bladderwrack (Fucus vesiculosus) to macrophages and lymphocytes significantly increased their ability to kill melanoma and lymphoma cells in vitro. The overall conclusion of these studies concerning the effect of fucoidan from Bladderwrack (Fucus vesiculosus) on tumor viability was that fucoidan significantly increased apoptosis in different tumor cell lines. The clinical significance is not clear.

Bladderwrack effect on angiogenesis

In a study performed by Cumashi et al. ³⁵ suggested that fucoidan from Bladderwrack (Fucus vesiculosus) did not inhibit angiogenesis.

Bladderwrack effects cyclooxygenase-1

The study performed by Parys et al. ²⁹ showed that fucophlorethols from Bladderwrack inhibited cyclo-oxygenase-1. The concentration needed for a relevant clinical effect may be too high to be realistic.

Bladderwrack effects on kidney stones

In a study performed by Veena et al. ⁴⁴, the administration of ethylene glycol to rats induced oxidative stress, which damaged the epithelium of the kidney which then might induce the formation of kidney stones. The results from this study showed that fucoidan from Bladderwrack reduced the oxidative stress in the kidney by significantly increasing the levels of antioxidant enzymes and non-enzymic anti-oxidants and significantly reducing the levels of lactate dehydrogenase, glycolic acid oxidase and xanthine oxidase. The three latter enzymes are responsible for metabolising oxalate. Oxalate and its metabolites are free radicals which cause oxidative stress. Furthermore the results showed that fucoidan from Bladderwrack significantly reduced the levels of alkaline phosphatase, γ-glutamyl transferase and β-glucuronidase, which are all indicators of cellular damage. Whether fucoidan from Bladderwrack could be used to prevent stone formation that is due to oxidative stress in the kidneys, remains to be clinically investigated, before any conclusion can be drawn.

Bladderwrack effect on muscle necrosis caused by snake venom

A study performed by Angulo and Lomonte ⁴⁵ showed that 135 kDa fucoidan from Bladderwrack reduced the muscle necrosis in mice by 70 to 95% when fucoidan was preincubated with the snake venom. Furthermore, the study also showed that when 90 and 270 μg of fucoidan was injected intramuscularly in mice immediately after intramuscular injection of snake venom, the muscle necrosis was reduced by approximately 50%. The latter experiment resembled reality more than the first experiment. The authors concluded that even when fucoidan from Bladderwrack injected immediately after a snake bite, there still will be a lot of muscle necrosis. The relatively high molecular weight of this fucoidan may reduce its diffusion and distribution in the tissue. It may be useful to do experiments using lower molecular weight fucoidans to monitor their effect on muscle necrosis after a snake bite.

Bladderwrack dosage

The appropriate dose of Bladderwrack depends on several factors such as your age, health, and several other conditions. At this time, there is not enough scientific information to determine an appropriate range of doses for Bladderwrack. However, most bladderwrack supplements come in 500-mg doses. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.

Bladderwrack side effects

At the present time no side effects had been reported with Bladderwrack supplement. Since Bladderwrack supplements contain iodine, which may be toxic at high doses, the recommended dose should not be exceeded. Bladderwrack supplements should not be taken at the same time as iodine preparations or medicines for the thyroid gland.

• When taken by mouth: Bladderwrack is POSSIBLY UNSAFE. It may contain high concentrations of iodine. Large amounts of iodine can cause or worsen some thyroid problems. It may also contain heavy metals, which can cause heavy metal poisoning.
• When applied to the skin: Bladderwrack is POSSIBLY SAFE when applied to the skin.

Safety in special populations and situations

Precautions should be taken in people with hypertension, kidney diseases and anemia (fucoidan may lead to reduced gastrointestinal absorption of iron).

• Pregnancy and breast-feeding: Bladderwrack is POSSIBLY UNSAFE to use when pregnant or breast-feeding. Don’t use it.
• Bleeding disorders: Bladderwrack might slow blood clotting. In theory, Bladderwrack might increase the risk of bruising or bleeding in people with bleeding disorders.
• Diabetes: Bladderwrack may affect blood sugar levels. If you have diabetes and take medications to lower your blood sugar, adding Bladderwrack might make your blood sugar drop too low. Monitor your blood sugar carefully.
• Infertility: Preliminary research suggests that taking Bladderwrack might make it harder for women to get pregnant.
• Iodine allergy: Bladderwrack contains significant amounts of iodine, which could cause an allergic reaction in sensitive people. Don’t use it.
• Surgery: Bladderwrack might slow blood clotting. There is a concern that it might cause extra bleeding during and after surgery. Stop taking Bladderwrack at least 2 weeks before surgery.
• Bladderwrack is contraindicated in following cases: hyperthyroidism (too much thyroid hormone), hypothyroidism (too little thyroid hormone), Graves’ disease or Basedow disease, Hashimoto’s thyroiditis, after partial resection of the thyroid gland, excess of iodine, pregnancy or lactation, children under five years, hypersensitivity to halogens, malicious diseases and tuberculosis ¹⁴.

Interactions with medications

Bladderwrack may interact with these drugs: lithium carbonate, thyroid medication, antihypertensive drugs, blood-diluting-agents and iodine containing drugs. In contrast, other literature considers the interaction with vitamin K-antagonists unlikely ⁴⁶. One case report of hyperthyroidism was published about a 60-year-old male patient diagnosed with bipolar disorder and under treatment with lithium. Since his myocardial infarction in 2001, the patient was treated with ramipril (1.25 mg 2 times daily), bisoprolol (2.5 mg/day), simvastatine (10 mg/day) and acetylsalicylic acid (100 mg/day). He was operated several times for an anal fistula, which is why he started taking a herbal product that contained besides 0.125 g of Bladderwrack also Rhamnus purshiana 0.170 g and Frangula 0.222 g per tablet. The patient took this preparation regularly (once a day). The thyroid hormones were controlled every 4 months. In 2008, he developed hyperthyroidism: T4: 2.13 ng/dl (normal levels 0.9-1.7) and TSH 0.01 mIU/l (normal levels 0.27-4.2). The condition was treatable with metamizole and thyroxine ⁴⁷.

• Lithium: Bladderwrack can contain significant amounts of iodine. Iodine can affect the thyroid. Lithium can also affect the thyroid. Taking iodine along with lithium might increase the thyroid too much.
• Medications for an overactive thyroid (antithyroid drugs): Bladderwrack can contain significant amounts of iodine. Iodine can affect the thyroid. Taking iodine along with medications for an overactive thyroid might decrease the thyroid too much, or may affect how antithyroid medications work. Do not take Bladderwrack if you are taking medications for an overactive thyroid. Some of antithyroid drugs include methimazole (Tapazole), potassium iodide (Thyro-Block), and others. Taking high doses of iodine with anti-thyroid medications can have an additive effect and could cause hypothyroidism.
• Medications that slow blood clotting (anticoagulant or antiplatelet drugs): Bladderwrack might slow blood clotting. Taking Bladderwrack along with medications that also slow clotting might increase the chances of bruising and bleeding. Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
• Herbs and supplements that might slow blood clotting: Bladderwrack might slow blood clotting. Taking Bladderwrack along with herbs that also slow clotting might increase the chances of bruising and bleeding. These herbs include angelica, clove, danshen, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng, poplar, red clover, turmeric, and others.
• Strontium: Bladderwrack contains alginate. Alginate can reduce the absorption of strontium. Taking Bladderwrack with strontium supplements might reduce the absorption of strontium.

Be watchful with this combination

• Medications changed by the liver (Cytochrome P450 2C8 (CYP2C8) substrates): Some medications are changed and broken down by the liver. Bladderwrack might decrease how quickly the liver breaks down some medications. Using Bladderwrack along with some medications that are broken down by the liver might increase the effects and side effects of some of these medications. Some medications changed by the liver include amiodarone (Cardarone), paclitaxel (Taxol); nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren) and ibuprofen (Motrin); rosiglitazone (Avandia); and others.
• Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates): Some medications are changed and broken down by the liver. Bladderwrack might decrease how quickly the liver breaks down some medications. Using Bladderwrack along with some medications that are broken down by the liver might increase the effects and side effects of some of these medications. Some medications changed by the liver include nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), and piroxicam (Feldene); celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar); and others.
• Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates): Some medications are changed and broken down by the liver. Bladderwrack might increase or decrease how quickly the liver breaks down some medications. Using Bladderwrack along with some medications that are broken down by the liver might increase or decrease the effects and side effects of some of these medications. Some medications changed by the liver include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.
• Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates): Some medications are changed and broken down by the liver. Bladderwrack might decrease how quickly the liver breaks down some medications. Using Bladderwrack along with some medications that are broken down by the liver might increase the effects and side effects of some of these medications. Some medications changed by the liver include alprazolam (Xanax), amlodipine (Norvasc), clarithromycin (Biaxin), cyclosporine (Sandimmune), erythromycin, lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), verapamil (Calan, Isoptin) and many others.

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