This article is part of our May 2021 special issue. Download the full issue here.
Reference
Jung SJ, Jang HY, Jung ES, et al. Effects of porphyra tenera supplementation on the immune system: A randomized, double-blind, and placebo-controlled clinical trial. Nutrients. 2020;12(6).
Design
Randomized, double-blind, placebo-controlled trial of 8-weeks duration
Objective
To determine if an extract of the seaweed Porphyra tenera (commonly known as nori or laver, and also referred to as Pyropia tenera) has measurable immune-enhancing effects and is safe in humans
Participants
A total of 111 participants out of 120 (men=20, women=100) completed the trial. Researchers equally recruited intervention and placebo groups (60 each). All participants were over the age of 50 at the start of the study and all had white blood cell (WBC) counts in the normal range (3,000 to 8,000 cells/µL).
Exclusion criteria was extensive and included the following: vaccination for influenza within the prior 3 months, body mass index (BMI) <18 kg/m2 or >35 kg/m2, presence of any acute disease process or chronic disease process, any supplementation with medications or functional foods associated with immune enhancement for the prior month, use of antipsychotic drugs in the prior 3 months, suspected alcoholism or drug abuse, participation in other human tests in the prior 3 months, those who are fertile and not on contraceptives, and those with abnormal liver or kidney function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] more than 3 times the upper normal limit, serum creatinine >2.0 mg/dL).
Intervention
Participants in the intervention group consumed 2.5 g/d of Porphyra tenera extract (PTE) in capsule form. The extraction process began as 100 kg of dried Porphyra tenera in 10% ethanol at 80 ± 2.0 degrees Celsius. The ethanol-extracted fluid was then processed through a 1-µm filter, lyophilized, and concentrated to 10–20 degrees Brix at 65–-70 degrees Celsius. The end product contained 68.45 (±20%) mg/g of a specific porphyran called porphyra334 (designating the chemical structure of the porphyran from this species).
The placebo was identical in weight, color, and flavor and contained 99.6% microcrystalline cellulose, 0.2% caramel coloring, and 0.2% silicon dioxide.
Primary Outcome Measures
Function of natural killer (NK) cells at week 0 versus week 8. Researchers measured this using CytoTox 96® Non-Radioactive Cytotoxicity Assay kit (Promega Corp, Madison, WI). Cytotoxicity was expressed as a percentage using both natural release and maximal release of lactate dehydrogenase (LDH), using K562 as target cells. K562 is a human leukemia cell line. Tests used effector/target cell ratios of 50:1, 25:1, and 12.5:1.
Secondary Outcome Measures
Researchers compared laboratory markers of immune augmentation from baseline (week 0) and end of study (week 8). This included: cytokines (interleukin-2 [IL-2], IL6, IL-12, interferon-gamma, and tumor necrosis factor-alpha [TNF-alpha]).
They assessed the incidence of upper respiratory infection (URI) at baseline (week 0), midway (week 4), and end of study (week 8) using the Wisconsin Upper Respiratory Symptom Survey.
All participants had 3 visits total: baseline visit (week 0), midway (week 4), and end of study (week 8).
Results
NK-cell activity level in the PTE group increased at every dilution level versus baseline (E:T=12.5:1 P=0.0004; E:T=25:1 P=0.0034; and E:T=50:1 P=0.0055). There was no increase in NK-cell activity in the placebo group.
While there was a tendency for improved NK-cell activity in the intervention versus placebo group, this did not reach statistical significance.
There were no differences in the secondary outcome measure of cytokine concentrations after 8 weeks between the 2 groups.
Safety indicators showed there was no significant difference between the 2 groups in laboratory tests, electrocardiograms, or vital signs.
Adverse reactions: abdominal discomfort=1, heartburn=4, contact dermatitis=1, left knee pain=1, chronic dermatitis=1, trigger finger=1, increased liver enzyme function tests=1, burn on back of hand=1. Of all the adverse reactions reported, the researchers deemed 6 cases as possibly caused by the intervention.
Key Findings
The primary outcome measure, NK-cell activity, showed there was improvement in the intervention group versus their baseline but no significant difference between the intervention and placebo groups.
Of the evaluable 111 participants, the incidence of URI at week 8 was 10 cases. There was no difference in cases between the 2 groups.
This 8-week study of Porphyra tenera extract showed overall safety of the preparation.
Commentary
In this short study, the effects of the Porphyra tenera extract (PTE) suggest that it increases NK-cell function activity. There was, however, no increase in cytokines and, thus, no systemic immune augmentation. This may be due to the short time course or due to a true lack of stimulation of cytokines from PTE. The low incidence of URIs over the 8-week study is not surprising given that the researchers recruited healthy volunteers who met stringent criteria.
The seaweed Porphyra tenera is a red algae and 1 of 133 Porphyra species (Porphyra spp). Out of the 133 species, 6 of them are largely cultivated: Porphyra yezoensis, Porphyra tenera, Porphyra haitanensis, Porphyra pseudolinearis, Porphyra dentata, and Porphyra angusta. Referred to as “nori” in Japan, “gim” or “kim” in Korea, and “zicai” in China, Porphyra spp are commonly consumed across the Asia-Pacific region in various forms.1 In English-speaking countries around the world and in many research papers, Porphyra spp is referred to as “laver.” In the United States and Canada, any of these terms may be used depending on the regional derivation of a given recipe. Nori sheets and snacks dominant the seaweed market in the United States, encompassing one-third of all sales, and growing.2
In a 2021 review of the compound porphyran, the authors summarize its effects as ‘antioxidation, anticancer, antiaging, antiallergic, immunomodulatory, hypoglycaemic, and hypolipidemic.
Various seaweeds the world over have been used as food due to their macronutrients, micronutrients, and ease of obtaining them along shorelines.3 Porphyra spp have readily extractable pigments, lipids, minerals, vitamins, amino acids, and polysaccharides, making it an intriguing candidate for commercial production of these nutrients.4 There are so many nutrients densely packed into this foodstuff, that it has been proposed as a feasible and sustainable functional food.5
Porphyran, an indigestible polysaccharide unique to Porphyra spp, is thought to be responsible for its immunomodulatory effects. Chemically, porphyran is a sulfated polysaccharide whose structure varies slightly among species.6 Immune-modulating action of polysaccharides is not surprising. They are often a constituent that provides immune-modulatory properties in plants, fungi, and bacteria commonly used for immune support (eg, 1-3 beta glucan).7
In a 2021 review of the compound porphyran, the authors summarize its effects as “antioxidation, anticancer, antiaging, antiallergic, immunomodulatory, hypoglycaemic, and hypolipidemic.”6 How porphyran influences immune function is paradoxical and appears to be context dependent, with both immune-suppressive and immune-augmentative effects suggested in rodent studies.8 The effects may depend on the physiological differences between acute and chronic inflammation and, more specifically, the immune requirements or aberrations involved in each.9 The net immune homeostatic effect of porphyran is suggested in animal studies showing benefits in conditions such as allergies and autoimmunity as well as infections and cancer.10-12
Another possible mechanism that can explain immune homeostasis is possible effects on the gut microbiota. The indigestible polysaccharide is a prebiotic and may alter the microbiota, thus affecting nearly every system in the body.13 In one study of mice with colitis induced by dextran sodium sulfate (DSS), Porphyra tenera extracts shifted the composition of the microbiome found in the mouse gut and ameliorated the colitis.14 In another rodent study, Porphyra yezoensis led to a 2-fold increase in secretory immunoglobulin A (IgA) in the cecum and synergized with another saccharide from the seaweed called glycerol galactoside, favorably shifting the microbiota and its metabolites.15
The study currently under review standardized the porphyran content to 68.45 (±20%) mg/g of porphyran334, the specific porphyrin found in this species of Porphyra. Whether this is ideal, whether the ethanol or 1-µm filter separated out other synergistic constituents, and how this extract compares to consuming the whole food are all lingering questions. While extraction may lead us to answer the question regarding which constituent is responsible for a given action, ethnobotanical use involves the whole seaweed prepared through roasting, boiling, frying, keeping raw, fermenting, etc. Arguably, when we are querying the action of a plant in its traditional use, we should also use traditional means of preparation to test physiological effects.
There is 1 caveat to any sourcing of food from seawater, and that is contamination. Seaweed generally contains alginate or other absorptive compounds that can bind pollutants, including microplastics, in open waters. Integration of smaller molecules such as petroleum distillates and nanoplastics are also a concern. The uptake of heavy metals into Porphyra spp is being studied as a means of bioremediation of contaminated waters, so the extent of their ability to take up pollutants should be top of mind. Fortunately, most of the nori snacks sold in the US are from cultivated sources, usually in Japan. It is important to make sure this detail is somewhere on the label.
Red algae, or Porphyra spp, will continue to be studied for the precise constituents that can someday be used as drug-like compounds in medicine. The presence of diverse nutrients and complex polysaccharides makes this seaweed an appealing whole food to recommend for our patients.
