The following literature review covers the specific ingredients included in YelpKelp® pet supplement to assist with certain issues encountered by animals which are not addressed solely from main nutrients. These ingredients include kelp/wakame, fucoidan, green lipped mussel, psyllium husk, yeast, kale powder and spirulina. The following reviews each individual ingredient, its benefits, potential safety issues, ideal doses and safety, where this is available from reviewed scientific sources. 

Kelp/wakame 

Kelp is microalgae, and this is a novel ingredient gaining much attention in pet food. Historically, gums from kelp have been used as natural thickening agents, but modern research has shown they have many more beneficial effects. Indeed, the alginate thickeners have been shown to be very safe, compared to chemically synthesised (poligeenan) forms, which have been linked to bowel inflammation and cancer in cats and dogs (Cohen, 2002; Weiner, 2014). 

Kelp typically provides, on a dry matter basis, 8% protein, 3% fat, 30% ash and 60% carbohydrates and is recommended for inclusion at levels of 0.5% or less in pet foods (Beynen, 2019) or 0.25% (Lewten, 2017). In addition, kelp contains a good mineral profile, which is very useful in providing a natural form of these nutrients in animal feed. Its high calcium content, in a natural form, is used in animal feed supplements to replace limestone. Kelp is known to accumulate selenium from seawater, a key antioxidant mineral which is lacking in many NZ feedstuffs. Selenium intake is important in many functions, including maintaining DNA integrity to prevent tumour development and support immune function. TEA-hydroiodide in brown kelp has been shown to promote fat digestion through its stimulation of lipase activity in animals. The species of kelp used dictates its actual makeup and can vary accordingly, especially regarding the presence of hormone analogues and polysaccharide profile. Feeding kelp at levels of 0.3% in a dog food diet did not affect palatability or intakes, when examined in a standard palatability test, but levels of 1% may reduce food consumption. 

Utilising naturally-occurring minerals has gained prominence in the last 20 years, as animal nutritionists move away from chemical versions, which have to be carefully balanced to prevent uptake problems leading the deficiencies, are not well retained in tissues and have higher toxicity, if fed to excess. 

Typical beneficial claims for kelp supplementation include better digestion, promoting a balanced gut microbe profile (due to the fibre content), immunity (due to antioxidant mineral content) and reducing oxidative stress. There is anecdotal and clinical evidence that kelp supplementation can assist in skin and hair condition, protein digestion (by 3% due to alginate; Murray et al., 1999) and supporting thyroid function (via iodine supply), which controls metabolism, obesity and cognitive function. 

In terms of safety, the main issues are to ensure the kelp source is analysed so that any heavy metals or toxic substances are confirmed to be absent. The inclusion rate should be based on mineral levels in the source, to ensure no overdosing of, particularly, iodine, which will lead to hyperthyroidism. Otherwise, reviews have stated that kelp supplementation, formulated correctly, are regarded as safe (Beynen, 2019). 

Green lipped mussel

Green lipped mussel powders and extracts are used for alleviating joint stiffness, pain and damage in animals, especially pets, due to the activity of glycogen and fatty acids content. Bui and Bierer (2003) fed 0.3% mussel powder to arthritic dogs and reported significant improvements in arthritis scores, joint pain and range of movement were recorded after six weeks of supplementation. Pollard et al. (2006) investigated the impact of feeding dogs with moderate joint degeneration with green lipped mussel extract for up to 112 days, and reported significant changes from day 56. These included reduced clinical signs of arthritis and improved musculoskeletal scoring. From reviewing 16 clinical trials on dogs, Aragon et al. (2007) found supplementation with green lipped mussel resulted in a ‘moderate’ level of comfort in dogs with osteoarthritis. Certain trials compared green lipped mussel supplementation with drug therapies such as Carprofen (Hielm-Bjorkman et al., 2009), and reported that the differences seen in alleviating chronic orthopaedic pain was enough to recommend the extract as an alternative for dogs unable to tolerate NSAIDS drug treatment. The levels of omega -3 fatty acids in green lipped mussels are associated with benefits in joint function – and Rialland et al. (2013) showed increases in plasma omega-3 levels in dogs receiving the supplement for 60 days, and reported that supplemented dogs had improved gait scores.

For cats, a controlled study reported that a diet containing GLM improved mobility in cats with degenerative joint disease over a nine-week feeding trial at a level of 74 mg GLM per 1000 kcal of diet (Lascelles et al., 2010). Johnson et al. (2020) reviewed the animal data on GLM in both cats and dogs, and concluded that supplementation did improve arthritic conditions, swelling, pain and gait scores, but doses should be appropriate for body weight, and may become expensive in larger dogs.

The LD50 on green lipped mussel (GLM) was studied by Chakraborty et al. (2014) and was established for a dose intake of 5 g/kg body weight per day. In a 90-day toxicity study with doses up to 2 g/kg BW and showed no adverse toxicological effects in animal behaviour or any organ analysis, leading then to ascribe a NOAEL of >2 g/kg BW. Other toxicological studies have been performed on GLM but not directly on the actives of this ingredient – rather the potential toxins that may have been introduced from the environment or via processing. Abdullah et al. (2014) examined the toxicology of heavy metals that may be present in GLM. This needs to be included on the Material Safety Data Sheet (MSDS) from suppliers with a guarantee of the absence of these toxic elements. Briggs et al. (2004) identified yessotoxin in GLM. Trials in Norway measured toxic okadaic acid in GLM (Torgersen et al., 2008). Pinnatoxins were highlighted in a Canadian paper, as these have been found in GLM sourced from Asia, the South Pacific and Northern Europe (McCarron et al., 2012). Toxoplasma has been found in some GLM, which can infect cats (Coupe et al., 2018). An inclusion level 1 g/d for a 25 kg dog falls well under the reported toxic levels for intake and is less than the reported NOAEL.

Fucoidan

Fucoidan is a sulphated, long chain polysaccharide found intercellularly and in the cell wall of brown macroalgae (Berteau and Mulloy, 2003). It is part of a diverse group of sulphated polysaccharides containing fucose (Citkowska et al., 2019). Fucoidans have been established to have beneficial biological activity and thus have been extensively researched for their use as a therapeutic or functional food in humans and animals. These have been reported to have anticoagulant, antithrombotic, antiviral, antitumour, immunomodulatory, antioxidant, and anti-inflammatory activities (Li et al., 2008). This review has been carried out to assess the published peer-reviewed research to establish recommended dosage rates, safety and efficacy of fucoidan in supplements fed to dogs. In particular, this review focusses on the evidence to support the effect of dietary fucoidan on gut health and immune function in dogs.

Fucoidan in MariVet® is sourced from two species of brown algae:
Fucus vesiculosus
Undaria pinnatifida

Safety

Fucoidan has been approved by Food and Drug Administration (FDA) as a Generally Recognized As Safe (GRAS) food ingredient. It is derived from Undaria pinnatifida and Fucus vesiculosus, which have been approved in the USA by Food and Drug Administration (FDA) in the GRAS category as food ingredients at levels up to 250 mg/day (ref: FDA GRAS notice as cited in Citkowska et al., 2019). In Europe preparations containing Fucus vesiculosus are registered in Austria, Belgium, France, Poland, Spain, and the United Kingdom (EMA report as cited in Citkowska et al., 2019). The basis of the GRAS status is toxicity work in laboratory animals administered fucoidan from various brown algae species; Undaria pinnatifida (Chung et al., 2010), Laminaria japonica (Li et al., 2005) and Cladosiphon okamuranus (Gideon et al., 2008). The undesired effect of anticoagulant activity seen with high concentrations of fucoidan in these studies has been deemed by the manufacturer’s submission to FDA (and approved by FDA reviewer) to pose little risk to animals as the intended dietary dose is 200-fold less than levels seen in the toxicology studies. A study in humans has shown that less than 1% of dietary fucoidan is absorbed into the bloodstream (FDA GRAS notice). Fucoidan (as non-anticoagulant sulphate polysaccharide; NASP) orally administered to dogs at 15-20mg/kg was well tolerated in clinical studies by Prasad et al. (2008).

In vitro evidence 

Anticoagulant (therapeutic not nutritional)

The anticoagulant activity of highly branched (high molecular weight) sulphated polysaccharides is considered an undesired side effect of some fucoidans. The structure of fucoidan can vary between species of brown algae, harvest locations and method of extraction and purification. Those that have been extracted and purified to remove anti-coagulation characteristics are described as non-anticoagulant polysaccharides (NASPs; Dockal et al., 2011). Nishino et al. (1994) identified and isolated a low molecular weight sulphated polysaccharide from Fucus vesiculosus (f.v.) fucoidan that showed no anticoagulant activity. Two groups of researchers observed procoagulant effects caused by fucoidan in vitro at concentrations between 5 nM and 100 nM (Liu et al., 2006; Zhang et al., 2014).  However, as the fucoidan concentration reaches 100 nM or greater researchers have found it starts to act as an anticoagulant (Liu et al., 2006). Zhang et al. (2015) evaluated Fucus vesiculosus (f.v.) and Undaria pinnatifida (u.p.) fucoidan (along with two other species of brown algae) to evaluate their potential to improve hemastasis in vitro. They found that f.v. fucoidan was the most consistent treatment to improve coagulation in vitro.

CDV Canine distemper virus (therapeutic not nutritional)

Canine distember virus is similar to measles that infects dogs and other carnivores. An in vitro study by Trejo-Avila et al. (2014) found that Cladosiphon okamuranus fucoidan exhibited anti-CDV activity. Trejo-Avila and colleagues attributed the anti CDV activity to mode of action seen in previous in vitro trial work, which identified that sulphated polysaccharides act via the inhibition of the entry of viruses into host cells (Damonte et al 2004, Ghosh et al 2009, Li et al2008 as cited in Trejo-Avila et al 2014) and block viral infections by interfering with the virus adsorption process (Baba et al 1988; Wang et al., 2012 as cited in Trejo-Avila et al., 2014).

Immunomodulatory activity (therapeutic not nutritional)

Mouse spleen lymphocytes cultured with fucoidan and arabiniogalactan (AG) at concentrations of 10-100 ug/ml exhibited cytotoxic activity against tumour cells in vitro. Macrophages treated with fucoidan and AG showed tumourcidal activity. Authors surmised that fucoidan and AG activate lymphocytes and macrophages by the production of cytokines and free radicals (Choi et al 2005). Fucoidan has an immunoenhancing effect on canine polymorphonuclear cells (PMNCs; Kim et al. 2011)

In vivo evidence

Laboratory animals (including probiotic claims – which can typically be used in nutritional supplements)

Liu et al. (2018) observed that supplementation with fucoidan modulated gut microbiota in mice fed a high fat diet. Undaria pinnatifida fucoidan doseage rates of 50 mg/kg/day and 100 mg/kg/day. Fucoidan was found to increase quantity of Bacteroidetes, Alloprevotella spp. and decrease Firmicutes, Staphylococcus and Streptococcus spp. in the gut of mice. This trial showed that fucoidan alleviated dyslipidemia (an imbalance of lipids that contributes to cardiovascular disease). Rats consuming 5% ground dried polysaccharide fraction (consisting largely of fucoidan and alginate) showed an increase in beneficial bacteria in the digestive tract of rats indicating potential prebiotic activity (Charoensiddhi et al., 2017). The polysaccharide was extracted from Ecklonia radiata.

An animal study showed the potential of fucoidan to suppress fat accumulation in mice fed a high fat diet. Mice fed 1% and 2% fucoidan showed decreased body weight, improved food efficiency, reduced lipid levels in plasma and improved liver steatosis compared to the non-treated group of mice (Kim et al., 2013).

Dockal et al. (2011) carried out in vivo work treating guinea pigs with induced haemophilia with fucoidan NASPs. Guinea pigs treated with f.v.fucoidan (0.1-1.6 mg/kg BW) showed improved blood clotting, indicating a potential of NASP fucoidan in the treatment of haemophilia. Lee et al. (2015) found that fucoidan prevented the progression of osteoarthritis in rats when administered at both 50 and 100 mg/kg BW/day.

A gastro-protective effect was observed in rats with aspirin-induced ulceration when fucoidan (20 mg/kg BW/day for 14 days) was administered with aspirin (Raghavendran et al., 2011). The authors findings indicated that the protective effect was mediated through immunomodulatory properties of fucoidan.

An in vitro trial administering fucoidan (100 and 200mg/kg/day for 4 weeks) to rats with Haymann nephritis showed evidence that fucoidan had a renoprotective effect and is a promising therapeutic agent (Zhang et al. 2005).

Cladosiphon fucoidan (0.05% and 0.5% in drinking water) was observed to prevent H. pylori infection (the causative organism associated with human gastric ulcers) in a dose dependent manner in Mongolian gerbils by exerting a protective effect on the gastric mucosal lining (Shibata et al., 2003 abstract only).

Pigs

Walsh et al. (2013) found that dietary fucoidan supplementation (240 ppm in feed) led to a reduced Enterobacteriaceaepopulation and an increased villous height and height:crypt depth ratio in the digestive tract in treated pigs, compared with pigs fed the basal diet. The benefit of these intestinal improvements includes reducing severity of diarrhoea and improving nutrition uptake from the diet. In this study, when fed in combination with laminarin (a storage polysaccharide found in brown algae) the beneficial effects on intestinal morphology and microbiota were lost. This was an 8 day study which was shorter than previous studies. The fucoidan was derived from Laminaria spp. 

Table 2 O’Sullivan et al 2010 summarises following ref trials – reporting prebiotic effects

Source	Active	Dose	Reference
Laminaria spp	Lamarin (0.112-0.446 g/kg) & fucoidan (0.36-0.89 g/kg)	1-4 g/kg feed	Gahan et al 2009
Laminaria spp	Fucoidan (0.24g/kg) & lamarin (0.3g/kg)	F 0.24 g/kg feed	McDonnell et al 2010
L. hyperborea	Fucoidan alone (0.24g/kg) & combination purified laminarin (0.3g/kg) & fucoidan (0.24g/kg)	0.7 – 5.6 g/kg feed	Lynch et al 2010a & b
L. digitata	Combination laminarin & fucoidan	?	O’Doherty et al 2010

 

Degenerative heart valve disease in dogs (therapeutic claim)

A pilot clinical study using four, elderly, small dogs with a history of heart disease was assessed by Tsai et al. (2020). The source of fucoidan in the case study was Laminaria japonica. Three of the four cases were given nutritional supplementation with fucoidan (60 mg/kg BW) and fucoxanthin (60 mg/kg BW) in addition to the usual heart disease drugs. The fourth case was only given the usual drug treatment. The three cases that were supplemented with fucoidan and fucoxanthin showed improvement in cardiac function index, after 3-6 months of continuous administration, whereas the fourth case, with no nutritional supplementation, showed no improvement in cardiac function and the animal continued to deteriorate over time. This is a small study which was promising, but larger studies need to be carried out to determine if improvements are statistically significant.

Fucoidan treatment of dogs with haemophilia A (therapeutic claim)

Prasad et al. (2008) carried out various clinical studies administering 15-20 mg/kg BW fucoidan AV513 orally to dogs with haemophilia A to determine the efficacy and safety of administration. This form (AV513) is a plant polysaccharide from brown seaweed classified as non-anticoagulant sulphated polysaccharide (NASP). Fucoidan AV513 was well tolerated by all dogs without any adverse events in all studies.

Janet Helen Fitton reviewed the role of fucoidan (Fitton 2008; 2011) in therapeutic applications The 2011 work was done for Marinova Pty Ltd – the manufacturers of MariVet. In the 2011 paper there are summary tables of the refs that discuss fucoidan effect on arthritis, liver disease and brain cell function. This covers in vitro, in vivo and clinical trial work. See included paper in email for full details.

NB. The claims for Fucoidan are from clinical trials which are concerned with veterinary problems – which typically need full drug registration if used as marketing claims on the product. It is LWT opinion that only nutritional claims should be made for this product to keep within the nutritional supplement definitions for regulatory bodies.

Spirulina 

As for kelp, spirulina (Arthrospira spp.) is a blue-green algae which contains various nutrients and has been traditionally used as a health food in humans. It is high (>60%) in protein, and rich in vitamins, minerals and essential fatty acids (including γ linolenic acid), and has been linked to immune, antioxidant, anti-inflammatory and antimicrobial benefits, when used in animal feed and pet food. Dogs fed diets containing 0.2% spirulina after a rabies vaccination had a significantly higher vaccine response and gut IgA production as well as better gut microbial stability compared to the control group (Satyaraj et al., 2021). In another review, Beynen (2019c) summarised benefits including improving immune parameters in irradiated dogs, and to promote health (rather vague) in cats and dogs. 

Although there have been mis-representation of the safety of spirulina use in animal feed, testing has shown it is safe, and that such scare stories have no basis. The USDA has included it on its GRAS register. Typical inclusion levels in pet foods range from 0.015-0.1% in dog food and 0.2% in cat food. 

Psyllium husk 

Psyllium husk has been used for many years as a preventative of constipation, providing good gut fill, promote gastric motility, support correct gut microbial profiles and to prevent digestive disorders and diarrhoea. As such, it has been reported to be beneficial in cats and dogs with constipation, controlling obesity as well as assisting with diabetes in pets (Chandler, 2012). 

Trials in dogs have shown that feeding 60 g (four tablespoons) per day to 22 police German Shepherd dogs (typical body weight 30-40 kg) on top of their regular diet reduced defaecation rates, improved faecal quality (firmness) and the dogs gained weight. Beneficial effects were seen beyond the supplementation period (Alves et al., 2021). In cats, up to 93% showed a reduction in constipation when supplemented with psyllium (Chandler et al., 2012). 

Fibre inclusion levels of 5 g/100 kcal of diet have been recommended to assist with weight loss (Chandler et al., 2012), but otherwise dog data is scarce, but we can work on building this into AAFCO to ensure fibre levels are balanced. 

Yeast 

Yeast comes in various forms, live, dried, cell wall and cell contents. Live yeasts are used in many animal feeds to promote correct gut bacteria, and are typically according probiotic status. Van Abeele et al. (2020) showed that feeding yeast improved microbial profiles and gut fermentation energy production in in vitro trials using cat and dog faecal material. Their safety is considered to be very good. They can selectively remove excess sugars from the gut digesta. Some are more refined than others, and some are by products of the brewing industry. Yeasts are associated with reducing acid producing bacteria, which can imbalance the hind gut causing diarrhoeal problems or encouraging the overgrowth of undesirable bacterial colonies. Yeast is a key source of B vitamins as well as protein and nucleotides (which are important in young animals for correct gut development). Yeast is commonly used as a palatability aid, especially in dog food, where brewer’s yeast seems to be the preferred type in dogs. Palatability tests have shown response to yeast inclusion, but not in cats (Beynen, 2019b). 

Trials with beagles supplemented with live yeast (1 g./kg body weight) showed a lower level of faecal E. coli and enterococci as well as higher fibre digestion (P<0.05) compared to the control, unsupplemented dogs (Stercova et al., 2016). Yeast cell wall has been shown to significantly increase beneficial organisms (P<0.05), such as Bifidobacter spp. in the gut of supplemented dogs (Beloshapka et al., 2013). Various leading cat and dog nutrition researchers have discussed the importance of using yeast and its derivates in maintaining correct gut microbial profiles, and, although cats are obligate carnivores, there is discussion that the benefits for them are similar to omnivores (Barry et al., 2012). Yeast can improve the digestion of fibre in the gut, producing B vitamins as part of the process and liberating energetic volatile fatty acids (VFAs) from the diet. Even broken up yeast can be beneficial, as shown by Lin et al. (2019) in their dog trial where beneficial gut organisms were significantly increased. In addition, blood immune parameters were measured in the supplemented dogs, and the results showed that feeding the yeast product reduced inflammation and enhanced immune capacity, likely due to the probiotic effect. 

Most yeast products are GRAS (generally regarded as safe) status. Dose rate is typically 1 g/d for dogs, or 1% generally in pet foods. 

References 

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Alves, J.C., Santos, A., Jorge, P. and Pitães, A., 2021. The use of soluble fibre for the management of chronic idiopathic large-bowel diarrhoea in police working dogs. BMC Veterinary Research, 17(1), pp.1-5. 

Aragon, C.L., Hofmeister, E.H. and Budsberg, S.C., 2007. Systematic review of clinical trials of treatments for osteoarthritis in dogs. Journal of the American Veterinary Medical Association, 230(4), pp.514-521. 

Barry, K.A., Middelbos, I.S., Vester Boler, B.M., Dowd, S.E., Suchodolski, J.S., Henrissat, B., Coutinho, P.M., White, B.A., Fahey Jr, G.C. and Swanson, K.S., 2012. Effects of dietary fiber on the feline gastrointestinal metagenome. Journal of Proteome Research, 11(12), pp.5924-5933. 

Beloshapka, A.N., Dowd, S.E., Suchodolski, J.S., Steiner, J.M., Duclos, L. and Swanson, K.S., 2013. Fecal microbial communities of healthy adult dogs fed raw meat-based diets with 

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Bui, L.M. and Bierer, T.L., 2003. Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs. Veterinary Therapeutics, 4(4), pp.397-407. 

Chakraborty, K., Joseph, D. and Chakkalakal, S.J., 2014. Toxicity profile of a nutraceutical formulation derived from green mussel Perna viridis. BioMed Research International, 2014. 

Chandler, M., 2012. DIETARY FIBRE IN DOGS AND CATS–ITS THERAPEUTIC IMPORTANCE. Veterinary Times, 42(40), pp.10-12. 

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Johnson, K.A., Lee, A.H. and Swanson, K.S., 2020. Nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats. Journal of the American Veterinary Medical Association, 256(12), pp.1335-1341. 

Kim, S.K. and Bhatnagar, I., 2011. Physical, chemical, and biological properties of wonder kelp—Laminaria. Advances in Food and Nutrition Research, 64, pp.85-96. 

Lascelles, B.D.X., DePuy, V., Thomson, A., Hansen, B., Marcellin‐Little, D.J., Biourge, V. and Bauer, J.E., 2010. Evaluation of a therapeutic diet for feline degenerative joint disease. Journal of Veterinary Internal Medicine, 24(3), pp.487-495. 

Lewter, 2017. Seaweeds for animal health. https://ivcjournal.com/seaweeds-animal-health 

Lin, C.Y., Alexander, C., Steelman, A.J., Warzecha, C.M., De Godoy, M.R. and Swanson, K.S., 2019. Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, nutrient digestibility, fecal fermentative end-products, fecal microbial populations, immune function, and diet palatability in adult dogs. Journal of Animal Science, 97(4), pp.1586-1599. 

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Pollard, B., Guilford, W.G., Ankenbauer-Perkins, K.L. and Hedderley, D., 2006. Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease. New Zealand Veterinary Journal, 54(3), pp.114-118. 

Rialland, P., Bichot, S., Lussier, B., Moreau, M., Beaudry, F., Del Castillo, J.R., Gauvin, D. and Troncy, E., 2013. Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis. Canadian Journal of Veterinary Research, 77(1), pp.66-74. 

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Fucoidan specific references

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