Over the last decade, few dietary supplements have been in the news as much as curcumin and turmeric, the item from which curcumin and related compounds are extracted. The background for modern western interest is much older. Turmeric (Curcuma longa) is a yellow spice and a traditional remedy that has been used as a medicine, condiment and flavoring since 600 BC. The rhizome (underground stem) is the part of the plant that is harvested and ground to make the spice. In the Indian Ayurvedic tradition of healing and cooking, the yellow spice turmeric warms and activates the digestion and is useful in many aspects of healing. Both Ayurveda and Traditional Chinese Medicine (TCM) associate turmeric with the health of the liver, skin, digestive, lung, joint and muscle tissues.

Some of the key bioactive constituents found in turmeric are three kinds of curcuminoids, curcumin, demethoxylcurcumin, and bisdemethoxylcurcumin. All three components are structurally similar, although curcumin seems to be the most effective of these three. Curcumin and the related curcuminoids (the mention of curcumin often being shorthand for all three) appear to affect human health through antioxidant activity and possible modulation of 5-lipo-oxygenase (LOX) and cyclo-oxygenase (COX) enzymes. The true health potential of curcuminoids has always been hindered by notoriously poor oral bioavailability. This has become generally accepted in recent years with numerous studies in humans demonstrating severe absorption shortcomings even when curcumin is consumed in large quantities. As a result, researchers have sought ways to overcome this limitation in bioavailability.

Too often overlooked with the focus on turmeric's curcuminoids is the presence of a number of other bioactives in the rhizome. These include immune-stimulating polysaccharides, volatile oils and yet other constituents. Beyond conventional turmeric lie one or more related species, such as Indonesia's Java turmeric, which exhibit special benefits not associated with Indian turmeric.

Curcumin and the Curcuminoids

Curcuminoid bioavailability is low for a variety of reasons. First, solubility in water is quite poor, especially so at the low pH (acid conditions) found in the stomach. Once food leaves the stomach, the pH rises in the upper small intestine and this presents other challenges inasmuch as curcuminoids are subject to damage by digestive fluids under these more neutral conditions. To make matters worse, poor absorption is compounded by their quick excretion from the system. The preponderance of the curcuminoids that are consumed is eliminated intact from the gut. Some curcuminoids are absorbed into the circulation, but almost none can be found in the blood in their free forms. Instead, they are almost entirely converted into water-soluble metabolites in the intestine and liver and appear in the blood as glucuronide forms.

Curcuminoids exhibit strong antioxidant activity, enhance cellular resistance to oxidative damage, and provide antioxidant protection against DNA damage. They also enhance the body's natural antioxidant glutathione levels, which in turn aids the liver in detoxification. Joint health is one area of significant benefit. In research on people with suboptimal joint function, curcuminoids have been found to support a healthy inflammatory response while promoting comfort and flexibility. There are many other areas of benefits. Curcuminoids exert several protective effects on the gastrointestinal tract, most likely via antioxidant activity. A double-blind trial found turmeric helpful for people with indigestion and effective in animal research in promoting healthy digestive function. Via antioxidant activity, curcuminoids may help promote cardiovascular health, especially by decreasing the propensity of low density lipoprotein (LDL) to oxidize. Research continues to suggest that oxidized LDL is one of the more pernicious forms of cholesterol in relation to cardiovascular health. The benefits of most interest, albeit ones that cannot be mentioned directly for any dietary supplement due to FDA regulations, are in the area of cancer.

Success in translating these potentials into tangible results has been limited by inherently poor intestinal absorption, rapid metabolism, and limited systemic bioavailability. These factors help to account for the somewhat spotty record of curcumin in clinical trials. Seeking to overcome these limitations, food ingredient formulators have begun to employ a variety of approaches for enhancing absorption and bioactivity. Many of these strategies are attempts to improve upon the age-old practice of consuming turmeric in fat-based sauces, such as in fat-rich curries. However, there exists uncertainty as to how the various commercially available offerings compare to each other in terms of either uptake or efficacy and this uncertainty leaves lay individuals, physicians and nutritionists with a dearth of data for evaluating products. A typical conundrum: is bioavailability calculated based on the active ingredient(s) only or on the total volume of a formula? Five times the bioavailability may not be an advance if it requires a formula with five times the weight for delivery, e.g., taking one capsule of curcuminoids versus taking five capsules to deliver the same amount of curcuminoids in four capsules worth of excipients.

Readers need to be extremely cautious regarding marketing claims as to the efficacy and bioavailability of curcumin products. For instance, one manufacturer of a curcumin product claims to offer a delivery format that upon ingestion leads to relatively large amounts of free curcumin in the blood, yet almost all other research indicates that the three curcuminoids are subject to rapid metabolism, both intestinal and hepatic. This means that almost no free curcumin can be found in the blood, only various metabolites and conjugates of these curcuminoids.^1,2Are these metabolites active? Curcumin metabolites retain at least some biological activity, but whether curcumin metabolites are as active as curcumin itself is not yet clear.^{3,4,5,6,7,8,9} In fact, the phenomenon in which turmeric extracts produce undetectable levels of free curcumin in plasma and nevertheless exhibit clinically significant effects speaks in favor of the biological relevance of curcuminoid metabolites.^10,11,12 Still, it is doubtful that the conjugates of curcuminoids are able to pass the blood-brain barrier.¹³ This latter factor suggests that at least some of the benefits attributed to regular turmeric consumption via the diet are not derived from the curcuminoids.

More traps for the unwary abound. For example, rodentbased studies of bioavailability can be misleading due to the fact that rodents exhibit different curcumin pharmacokinetics compared to humans.¹⁴ Sometimes even claims regarding increased bioavailability in humans have failed spectacularly when revisited. One such claim is that inclusion of black pepper or one of its constituents, i.e., piperine (Bioperine), improves curcumin uptake. An early research study reported that a small quantity of piperine can enhance curcumin bioavailability "20-fold" in humans.¹⁵ In opposition to this conclusion, a recent independent analysis reported finding little increase in plasma free curcuminoid levels when using the commercially available C 3 Complex plus piperine systems.¹⁶ As another example of the issues that can arise is an ambiguous representation of the dosage tested in clinical trials. On this point, see the letters in a recent controversy over claims for a particular curcumin for exercise-induced muscle damage based on published research in which the dosages administered were, at the very least, unclear.¹⁷

Dietary Supplement Options
Various supplement options are examined in detail in "Beyond Yellow Curry: Assessing Commercial Curcumin Absorption Technologies," which can be freely downloaded from PubMed.¹⁸ This article and related background research suggest that particularly noteworthy commercial products based on concentrated curcuminoids include CurcuWIN™ (OmniActive Health Technology),¹⁹ Meriva® (Indena) and Theracurmin™ (Theravalues/P.L. Thomas).

What About Whole Turmeric?
Great emphasis has been placed on the curcuminoids found in turmeric, so much so that the average person might well believe that there is little else of worth in this spice. Nothing could be further from the truth! There are at least 200 known compounds in turmeric root, dozens of which appear to be active. Aside from the three major curcuminoids, known active compounds and families of compounds in turmeric include â-elemene, bisacurone, calebin A, curcumene, curdione, cyclocurcumin, volatile/fixed oils (turmerones and related compounds), bisabocurcumin, various proteins (biologically active molecular carriers, etc.), special dietary fibers (enhancers of the bioavailability of biologically active molecules), and acidic polysaccharides (immunomodulators).²⁰

According to one company involved in advanced product development in conjunction with the famous curcumin researcher, Bharat B. Aggarwal, "the challenge is to recreate the curcumin inside the turmeric matrix effectively." It claims to have developed a novel way to recreate the turmeric matrix with active curcuminoids by a method known as Polar- Nonpolar Sandwich (PNS) technology. Potential benefits of this product, known by two different names, Cureit and Acumin (the latter in the American market via Novel Ingredients), are likely to be much broader than those that can be traced to curcuminoids alone. This approach has been discussed in these pages before—see "Beyond Synergy–the Entourage Effect in Nutrition and Herbalism" (TotalHealth Sep 2015). This new item, which consists of nothing other than specially treated turmeric without the addition of piperine, nanoparticles, liposomes, micelles, phospholipid complexes or their analogs, is being presented as supporting bone and joint health, cognitive function and general anti-aging benefits.²¹

Several clinical studies have been completed, although not yet published. A study conducted in rheumatoid arthritis patients showed that Acumin was beneficial. Active rheumatoid arthritis patients who received Acumin (either 250 or 500 mg twice per day) for a period of 90 days reported a statistically significant decrease in their clinical symptoms towards the end of the study.²² This result is similar to that reported with the use of 1,000 mg of a special delivery curcumin preparations, such as Meriva, over the same time range.²³ Another Acumin clinical study examined comparative bioavailability issues, although these may not be particularly relevant given that Acumin is not a pure curcuminoid product. Both of these studies currently are under review for publication.

Java Turmeric
Beyond Indian turmeric, there is a related item that in at least one traditional Asian medical system is considered to be superior for many health purposes. Known as Java turmeric or Javanese turmeric due to its origins in Indonesia, C. xanthorrhiza is a plant of the ginger family Zingiberaceae, which grows widely in Southeast Asia. Java turmeric is related to the better known Indian turmeric and there is a large overlap in traditional and modern herbal uses, including anti-inflammatory, anticarcinogenic, wound healing and serum cholesterol-lowering.²⁴ A number of constituents differ between Java and ordinary turmeric. Xanthorrhizol, in particular, is a sesquiterpenoid compound unique to Java turmeric. Among its known special benefits are hepatoprotective actions. An extract of the whole rhizome, likewise, has been shown to support liver health.²⁵

An area that has been under-explored with Java turmeric, but in which this plant may exhibit special benefits, is immune function. For instance, in one animal experiment, chronic ingestion of an extract increased the proportion of splenic T cells.²⁶ An in vitro trial examining mechanisms of action for immune response found that a polysaccharide in Java turmeric stimulates the immune functions of macrophages.²⁷ Among the differences between Java turmeric and Indian turmeric are the following:

• composition of the dried rhizome—curcuminoids (1.6–2.2 percent), xanthorrhizol (1.48–1.63 percent)
• three nonphenolic diarylhepatanoids support normal inflammation response
• acceleration of the metabolism of the lipids from extrahepatic tissues to the liver, thus increasing the excretion of cholesterol via the bile
• secretion of bile acids (and bilirubin) and improvement in bile composition leading to the cholesterol found in bile being more likely to remain in solution (important for gallbladder function)
• unlike bisdesmethoxycurcumin, does not inhibit bile flow

In powdered bulk form and other deliveries, Java turmeric has been available in the US via specialized Asian product sellers for decades and in Europe for centuries. (Indonesia was under Dutch rule from the mid-17th Century until 1949.) CUR-XZOL™ (Curcuma xanthorrhiza Roxb.) is a commercially available source of Java that is manufactured in a major Indonesian pharmaceutical facility. It is fully characterized and contains a specified amount of xanthorrhizol. On amazon.com it can be found in an American formula as "WILD JAVA TURMERIC."

1. Ireson CR, Jones DJ, Orr S, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev2002;11(1):105–11.
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10. Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894–900.
11. Mohammadi A, Sahebkar A, Iranshahi M, et al. Effects of Supplementation with Curcuminoids on Dyslipidemia in Obese Patients: A Randomized Crossover Trial. Phytother Res. 2013 Mar;27(3):374–9.
12. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004;10:6847–54.
13. Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999 Apr;27(4):486–94.
14. Ireson CR, Jones DJ, Orr S, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 2002;11(1):105–11.
15. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353–6.
16. Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450–62.
17. http://www.nutritionaloutlook.com/sports-energy/curcumin-reduces-symptoms-exercise-induced-muscle-damage-study-suggests.
18. Douglass BJ, Clouatre DL. Beyond Yellow Curry: Assessing Commercial Curcumin Absorption Technologies. J Am Coll Nutr. 2015;34(4):347–58. Downloadable from https://www.ncbi.nlm.nih.gov/pubmed/25856323.
19. Oliver JM, Stoner L, Rowlands DS, Caldwell AR, Sanders E, Kreutzer A, Mitchell JB, Purpura M, Jäger R. Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study. J Nutr Metab. 2016;2016:1089653.
20. http://www.aureabiolabs.com/wp-content/uploads/2016/10/Aurea-Newsletter_August.pdf
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23. Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G. Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis. Panminerva Med. 2010 Jun;52(2 Suppl 1):55–62.
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26. Yasni S, Yoshiie K, Oda H, Sugano M, Imaizumi K. Dietary Curcuma xanthorrhiza Roxb. increases mitogenic responses of splenic lymphocytes in rats, and alters populations of the lymphocytes in mice. J Nutr Sci Vitaminol (Tokyo). 1993 Aug;39(4):345–54.
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Americans are not accustomed to considering the liver as a factor in health and disease. We fear conditions such as heart disease, obesity and cancer, but seldom do we link any of these to derangements in the liver. This is unfortunate because hepatic functions rule much of the body. The liver is the largest organ in the body. It is so large, in fact, that it fills the entire upper right-hand side of the abdominal cavity and spills over into the left-hand side. The bulk of the liver consists of many small functional units called liver lobules; in humans there may be as many as 100,000 lobules constituting the mass of the organ. The size and complexity of the liver is related to the multitude of roles that this organ plays in the body. Considering the indispensable quality of these roles, it is fortunate that nature has built considerable redundancy into the organ. As much as 60 percent of the liver can be damaged without causing obvious illness and, given the proper care, even a severely damaged liver can largely regenerate itself.

Functions Of The Liver¹
Most conspicuous among the functions of the liver is the secretion of bile. Bile goes first into the gallbladder and then into the small intestine, where it acts to break fat globules into small droplets. The role of bile in the body is more complex than this, however, and is related to the liver’s other functions. These can be divided between the storage and filtration of blood, on the one hand, and involvement in the majority of all of the body's metabolic functions, on the other hand. The range and significance of the liver’s participation in metabolic functions can be seen even from the peculiar fact that the hepatic portal vein delivers blood directly from the gastrointestinal tract to the liver before this nutrient-rich blood is distributed to the rest of the body. All liver cells are continuously in contact with blood from the portal vein. In other words, the liver is to the metabolic system what the heart is to the circulatory system.

Blood equivalent to just under 30 percent of the heart’s resting output constantly flows through the liver via the portal vein and the hepatic artery. Cirrhosis of the liver, which can result from alcoholism or any number of toxic and viral causes, radically restricts portal vein blood flow because fibrous tissues constrict around the veins that run through the liver. As much as 10 percent of all blood typically is found in the liver and the liver can expand to hold even an entire liter upon demand. Similarly, roughly 50 percent of the lymph formed in the body at rest originates with the liver.

As might be expected from the degree of blood flow through the liver, detoxification is a primary role of the organ. Large macrophages lining liver tissues routinely capture and degrade the bacteria almost always found in the blood of the portal vein, i.e., in blood that has just come from the digestive tract. The liver likewise detoxifies and excretes into the bile excess and degraded hormones, poisons and drugs such as antibiotics, and the end products of red blood cell disintegration. Indeed, one of the great benefits of soluble and semi-soluble fibers in the diet is that these capture and prevent the reabsorption of many toxins that had been disposed of by the liver via bile salts.

The two preceding functions of the liver, bile secretion and blood filtration, thus are quite closely linked. The third or metabolic function of the liver is as varied as are the first two. This function encompasses the metabolism of carbohydrates, fats and proteins as well as the activation and storage of many vitamins.

Normal blood glucose levels are maintained primarily by the liver. Although a certain amount of the glucose entering the system after meals is disposed of via the lean peripheral tissues, for the most part it is the liver that either dispenses or withdraws sugar from the blood as needed. This means that it is the liver that produces and stores the preponderance of glycogen found in the body, which converts fructose to glucose, and which creates new glucose from non-carbohydrate sources when blood glucose levels fall too low. It also is the liver that is the site of the production of most of the aspartate, succinate, and other by-products of the Citric Acid or Krebs Cycle for use in the body.

With regard to fats, the liver performs a number of special operations. For instance, immediately following meals, the chief site for the creation of fat from excess calories derived from carbohydrates and proteins is the liver. Preformed fats consumed in meals, of course, are digested and assimilated through the action of bile, as already mentioned. The lipoproteins that carry all of these fats throughout the body for storage, for the production of hormones and for energy likewise come from the liver. The cholesterol and the phospholipids found in every cell in the body are largely synthesized in the liver. Finally, much of the oxidation of fatty acids for energy takes place in the liver.

Protein metabolism in the liver may actually be more important to sustained good health than either carbohydrate or fat metabolism. Proteins are necessary for the integrity of all tissues, but this role comes at a high price. The degradation of proteins produces ammonia, which is highly toxic even in small amounts. It is the liver that removes ammonia from the blood and transforms it into urea for disposal by the kidneys. Similarly, it is the liver that deconstructs proteins so that they can be used as sources of energy. The amount of such degradation that takes place outside of the liver is of little consequence to the body. Virtually all of the numerous proteins found in the blood come from the liver, and these proteins control clotting, blood volume and other such duties. Finally, nonessential amino acids and other compounds constructed from amino acids are usually formed in the liver.

Quite a number of nutrients are stored in the liver. Iron is the best known of these, but the vitamins A, B-12 and D also are stored in this organ. As a related function, it should be remembered that many vitamins can be used by the body only after they have been converted into their co-enzymatic forms, and these conversions typically take place either directly in the liver or through one of the liver’s actions.

Optimization Of Liver Functions
Since the liver performs so many roles, it is critical that the vitality of the organ be carefully nurtured. This nurturing consists of three facets. First, it is important to protect the liver from the effects of the various toxins with which it routinely comes into contact. These toxins have many sources. Bacteria and viruses produce toxins, as does the immune system when it combats these. The ammonia from protein metabolism is an ever-present toxin. And then there are environmental toxins, some natural and some produced by modern technology. The former include the aflatoxins found in virtually all peanut products, whereas the latter include pesticide residues, dioxin from paper production and other sources, and the multitude of halogenated products and phthalates now found everywhere, e.g., as plastics.

A second approach to improving liver function is to encourage the secretion of bile by the liver and then the promotion of bile outflow from the gallbladder. The items involved usually are lumped together under the name of “lipotropics.” These can be divided between choleretics or items encouraging the production of bile, and cholagogues, substances that lead to the release of bile from the gallbladder. Inasmuch as toxins are often removed from the body via the bile and, likewise, the inability of the liver to detoxify properly can lead to the infiltration of fatty deposits into the liver, both of these approaches are needed to safeguard liver health. Both the basic bile secretory functions and attendant removal of bile by the gallbladder must be addressed.

The third approach to improving liver function involves adding substances to the diet that aid the liver in its actions of transforming proteins, fats and carbohydrates, in changing vitamins into their actives forms, and in pursuing its other metabolic functions.

Common Liver Protectants

Milk Thistle Extract/Silymarin
Silymarin refers to the most active three components of milk thistle. Milk thistle has long been used traditionally to protect and treat the liver, where it increases the content of the antioxidant enzyme glutathione (GSH). Silymarin neutralizes toxins and is known to help regenerate damaged livers and to improve liver function.² Silymarin can take over many of the detoxification functions of the liver. Since there can be a rebound effect similar to that found with vitamin C after long and extensive use of silymarin, it is advisable to cut back usage slowly after a course of treatment.

Dandelion Root Extract
Dandelion root is a classic liver tonic. Dandelion is a “bitter” herb that clears the liver and improves its functions. The presence of fats in the diet and likewise the day-to-day production hormones that are made from fats represent heavy demands placed upon the liver, which must routinely transforms the fats and deactivate the breakdown products of the hormones. In women inadequate liver function plays a primary role in PMS and in difficult menopause. In men the results of poor liver function are just as destructive, e.g., constipation, heart disease and related problems, perhaps increased/premature hair loss. Dandelion is noted for its ability to aid in a multitude of disorders involving the liver.³

Barberry Root
One active constituent of barberry is berberine. Traditionally, barberry has been used to treat high fevers, jaundice and chronic dysentery. The alkaloid possesses antibacterial and antifungal aspects, including actions against Candida albicans. In general, berberines are considered to have a soothing effect upon the mucous membranes, including those that line the gastro-intestinal tract. Barberry promotes both the secretion of bile and its elimination via the gallbladder.⁴

Licorice Root
Licorice root is characterized by a remarkably extensive number of healing properties. With regard to the liver, the glycyrrhizin content represents the root’s chief benefit. Glycyrrhizin is known to protect against toxin-induced liver damage and to improve the response to viral hepatitis. Unwanted aldosterone effects from the acid are rare from extracts and generally are limited to licorice-flavored sweets eaten in excess.⁵

Artichoke Extract
Cynarin and other caffeylquinic acids in the artichoke promote bile secretion and flow. Artichoke extracts are used extensively in Europe to protect the liver against toxins and to encourage the regeneration of the liver after damage. Indeed, artichoke extracts have been shown to lower cholesterol and triglyceride levels in humans.⁶

Fumitory
Fumitory regularizes the flow of bile from the gallbladder and also stimulates the secretion of bile by the liver. It has long been used to improve response to obstructed bile flow, such as nausea and pain from the gallbladder.⁷

Turmeric/Curcumin A plant related to ginger, turmeric is a source of curcumin. This highly colored pigment possesses strong anti-inflammatory properties comparable to those of hydrocortisone, but without the toxicity. Turmeric has a long historical use in the treatment of liver disorders, including jaundice. Curcumin is a powerful antioxidant and a protectant against toxins. Turmeric also inhibits organisms that cause the inflammation of the gallbladder.⁸

Bupleurum and Black Radish
These items are among the standards in Asian medicine for treating hepatic disorders. They commonly are used in cases of chronic hepatitis. They are said to “drain excess fire” from the liver, improve jaundice and generally to promote the excretion of bile. Specially prepared radish is a standard for liver problems in India as well as in China and Japan.⁹

Lipoic Acid
Lipoic Acid, also known as thioctic acid, is a “conditional” vitamin that can be made in limited quantities by the body. Animal experiments have yielded interesting results. Lipoic acid can positively influence some aspects of diabetes, including the neuropathies associated with the disease. As is true of L-carnitine, lipoic acid appears to have immune enhancing properties and also to be able to help protect against atherosclerosis. It contains sulfur and is closely linked to the functions of alpha-ketoglutarate and other alphaketoacids in energy production cycles. Lipoic acid, through its role in the functioning of acetyl-coenzyme A leading into the Citric Acid Cycle, may improve the functioning of the B vitamins and energy levels. This central role in the basic energy production cycle likely serves to shunt calories into activity and away from storage as fats that so often characterizes reduced metabolism.¹⁰ Only trace amounts of lipoic acid are needed by the body, yet by improving the liver’s activities in key metabolic pathways, this substance may encourage the more productive use of other nutrients.

Conclusion
The liver is a centrally important organ in digestion, the clearance of toxins, and basic metabolism. Many issues in physiology that often are treated directly with pharmaceuticals might be indirectly and more safely addressed by supporting the functions of the liver. A number of inexpensive and readily available herb and other natural compounds can be used for these purposes.

References

1. These points are aspects of general anatomy and physiology, for which see: Cecil Textbook of Medicine (fifteenth edition, 1979) under various headings; Arthur C. Guyton, Textbook of Medical Physiology (eighth edition, 1991) 744ff; Gary A. Thibodeau, Structure & Function of the Body (ninth edition, 1992) 201–2, 307–9, 320–1.
2. Planta Medica 50 (1984) 248–50; Plant Flavonoids in Biology and Medicine (1986) 545–58.
3. Michael Weiner, Weiner’s Herbal (Mill Valley, CA: Quantum Books, 2nd edition, 1990).
4. British Herbal Pharmacopoeia (British Herbal Medical Association, 1983). 5. H. Suzuki, et al., “Effects of glycyrrhizin on biochemical tests in patients with chronic hepatitis,” Asian Medical Journal 26 (1984) 423–38; Y. Kiso, et al., “Mechanism of antihepatotoxic activity of glycyrrhizin,” Planta Medica 50 (1984) 298–302.
5. T. Maros, et al., “The effects of Cynara scolymus extracts on the regeneration off the rat liver,” Arzneim-Forsch. 16 (1966) 127–9 and 18 (1968) 884–6; on hyperliperdemia, see 25 (1975) 1,311–14.
6. P. Forgacs, et al., Pl. Med. Phyt. 16 (1982) 99ff.
7. Y. Kiso, et al., “Antihepatotoxic principles of curcuma longa rhizomes,” Planta Med 49 (1983) 185–7.
8. Oriental Materia Medica.
9. Maria C. Linder, Nutritional Biochemistry and Metabolism (Elsevier, 1991) 122; H. Ohmari et. al., I. “Augmentation of the antibody response by lipoic acid in mice.” II. “Restoration of the antibody response in immunosuppressed mice,” Japanese Journal of Pharmacology 42 (1986) 275–80; G. Sachse and B. Willms, “Efficiency of thioctic acid in the therapy of peripheral diabetic neuropathy.” Hormone and Metabolic Research 9, Supplement (1980) 105; J.C.H. Shih, “Atherosclerosis in Japanese quail and the effect of lipoic acid.” Fed. Proc. 42 (1983) 2494–7.