POLYSACCHARIDES

Complex carbohydrates occur in all plants and fungi and account for important therapeutic properties in many of them. This discussion focuses on polysaccharides other than starch that do not serve as glucose sources for non-ruminants. The role of polysaccharides in the ruminant digestive tract is different and it is sufficiently discussed in standard texts, so it is not reviewed here.

Polysaccharides are high-molecular-weight chains composed of monosaccharide units attached from the hemiacetal hydroxyl group on the first carbon of one and any other hydroxyl group on the next. Polysaccharides do not crystallize and are tasteless or mildly sweet at best. They are generally brown or white in color. Polyuronides are polysaccharides that also contain some uronic acid units. They have essentially the same properties as polysaccharides.

Although most complex carbohydrates are technically water insoluble, they do form gels to varying degrees when mixed with water. Basically, water adsorbs into the hydrophilic pockets within and among the polysaccharide chains, leading to partial weak association of chains via hydrogen bonding or coordination. These gels are generally reversible with addition of heat, although warm water is most effective in the creation of most gels. Some gel formation involves the formation of full covalent bonds and may be irreversible. These gels ultimately end up as insoluble precipitates.

The terms mucilage and gum are often used to describe the hydrocolloid gel that results when polysaccharides are mixed with water. The technically correct use of these terms is intermittent at best, although it is fortunate that this does not significantly affect therapeutic use. A mucilage is technically a heterogeneous branched polysaccharide (i.e., one made up of multiple different monosaccharide monomers) that is normally found in plant cells associated with special canals or cells; it is particularly common in external seed coats. A gum is a heterogeneous polyuronide that is usually formed in response to trauma.

Polysaccharides make up the main portion of dietary fiber, although these highly complex molecular mixtures also often contain lignins and other noncarbohydrate. Thus, dietary fiber and polysaccharides are not completely synonymous but are closely related. So-called soluble dietary fiber contains a higher percentage of gel-forming polysaccharides compared with insoluble dietary fiber.

The molecular mechanisms of action of polysaccharides and polyuronides have been most extensively studied as the dietary fiber portion of foods. Dietary fiber, likely through short-chain fatty acid breakdown products produced by gut microbes, decreases hepatic synthesis of fatty acids and thus reduces triglyceridemia. Fiber also increases bile acid turnover and modifies its synthesis, thus lowering systemic cholesterolemia. Only soluble fibers have these effects consistently. Hypolipidemic effects generally require several weeks of treatment, as gene expression, microbial flora alterations, and other changes take time to occur after exposure to high-fiber diets.

Dietary fiber induces satiety and slow gastric emptying, apparently according to the viscosity of the material. In a normal nonruminant gut, fiber tends to reduce transit time, with variable strength depending on the type of fiber involved. When diarrhea is present, however, dietary fiber actually binds the stool and increases transit time. Fiber has also been shown in many studies to decrease formation of colon cancer in animals exposed to carcinogens, although much work remains to be done to elucidate the degree to which this effect is clinically relevant. The anticarcinogenic effects and many other properties of fiber may in part relate to its multifactorial effects on the gut flora, although at present, the exact effects of various types and amounts of fiber to be used for different durations of time have not been completely clarified. Fiber also reduces paracellular gut permeability in rodents.

Fiber in the gut delays absorption of glucose, which, in turn, reduces insulin responses. High-fiber diets have been extensively studied for their antidiabetic properties.

Gel-forming complex carbohydrates also act as demulcents or emollients. A demulcent is hydrating to the skin and moderately anti-inflammatory; it protects the gastric and esophageal epithelium from acid or other erosive materials. No research is available on the exact mechanisms involved in demulcent effects, other than the obvious mechanical barrier functions that they perform on tissue surfaces. The demulcent property is exploited clinically primarily to treat inflammatory conditions of the skin and digestive system. The immediate soothing effect of application of infusions of demulcent herbs has been demonstrated in clinical trials on humans with pharyngitis.

Demulcents are believed to stimulate mucus production in the respiratory and urinary tracts via nerve reflexes, although this hypothesis has not been systematically assessed. One study of Althaea officinalis (marsh-mallow) root extract and polysaccharide isolate in cats showed that, at 100 and 50mg/kg body weight doses, respectively, they acted as significantly more potent antitussives than the drug prenoxdiazine. Because complex polysaccharides are very unlikely to circulate in any quantity, it is difficult to imagine how they could act as antitussives, unless this occurs through some indirect mechanism.

Complex polysaccharides administered orally have repeatedly been shown to have immunostimulating effects. For example, polysaccharides from the root of Rehmannia glutinosa, an Asian medicinal herb, have been shown to inhibit complement. The polysaccharides of the root of Glycyrrhiza uralensis (gan cao), a close relative of licorice, and of the seed of Plantago asiatica (Asian plantain) have been shown to stimulate phagocytosis. Sulfated galactans from thallus of Chondrus ocellatus, a Chinese seaweed related to Chondrus crispus (Irish “moss,” also actually a seaweed), have shown multiple complex effects on various components of the immune system. Detailed molecular mechanisms for the immune effects of polysaccharides are largely unknown, although in the case of Echinacea purpurea leaf and flower polysaccharides, evidence suggests that its immune-stimulating effects are due to changes in levels of various interleukins. Evidence for the proposed immunomodulating effects of polysaccharides, that is, their ability to both stimulate and suppress various immune cells depending on the milieu, was not located (Actions of Gel-Forming Polysaccharides).

Actions of Gel-Forming Polysaccharides
• Decrease hepatic fatty acid synthesis
• Increase bile acid turnover
• Modify bile acid synthesis
• Reduce hyperlipidemia
• Slow gastric emptying
• Increase satiety
• Reduce transit time
• Bind diarrhea
• Have anticarcinogenic effects in the colon
• Modulate gut flora
• Reduce gut permeability
• Delay glucose absorption
• Provide demulcent/emollient effects — hydrate skin, act as anti-inflammatory topically, protect from stomach acid
• Antitussive
• Promote production of mucus in the respiratory and urinary tracts
• Act as immunostimulator

Polysaccharides are extremely safe. They have no known toxic effects. Occasionally, some dietary fibers can cause loose stools in nonruminants. Highly gel-forming gums and mucilages can swell sufficiently to cause mechanical obstruction of the esophagus or small intestines, although this is very rare at usual levels of intake.

Polysaccharides can delay absorption of some drugs, such as digoxin, which is enterohepatically resorbed. Monitoring the blood levels of drugs in animals fed large amounts of polysaccharides may be necessary to ensure therapeutic effects in some cases (Select Polysaccharide-Rich Herbs).

Select Polysaccharide-Rich Herbs
Angiosperms
Alcea rosea (hollyhock)
Aloe vera (aloe vera) gel
Althaea officinal is (marsh mallow)
Astragalus membranaceus (astragalus)
Coix lachryma jobi (Job’s tears, yi yi ren)
Elymus repens (couch grass)
Fucus vesiculosus (bladderwrack)
Clycyrrhiza glabra (licorice)
Clycyrrhiza uralensis (gan cao)
Opuntia spp (prickly pear)
Sphaeralcea parvifolia
• Symphytum officinale (comfrey)
Ulmus rubra (slippery elm)*
Zea mays (corn, maize)
Fungi
Ganoderma lucidum (shiitake)
Lentinula edodes (reishi)
Trametes versicolor (yunzhi, cloud mushroom)
Lichen
Cetraria islandica (Icelandic “moss”)
Red Algae
Chondrus crispus (Irish “moss”)
*Threatened in the wild. Use only cultivated sources.