Appliance of science

Isle of sweets in fenugreek
The quest for a naturally occurring substance that can favourably affect carbohydrate/insulin-regulating metabolism in humans is ever ongoing. Fenugreek (Trigonella foenumgraecum), a seed native to southern Europe, the Mediterranean area and western Asia, and now cultivated from Europe to China, is the latest candidate that has historically been used to treat what are now known as carbohydrate metabolism disorders, including diabetes.1

In the past decade, researchers have discovered that a non-protein amino acid found in the seed of fenugreek, (2S,3R,4S)-4-hydroxyisoleucine (4-ILE), can potentiate the amount of insulin released from beta cells in the islets of Langerhans located in the pancreas (animal and human), enhance the responsiveness of tissues to insulin and even improve carbohydrate metabolism in non-diabetic animals.1,2,3,4,5 4-ILE appears to exert its influence on the pancreatic islet cells by working in concert with glucose: the insulin-releasing effect of glucose (entering the blood from ingested foods) is magnified by the concurrent presence of 4-ILE.1,3 For people with type 2 diabetes, this could mean improved blood-sugar disposal and a resultant ability to reduce anti-diabetic medication.6

For athletes and bodybuilders, this could mean enhanced carbohydrate replenishment in exercised muscles, increased creatine retention in muscle and possibly greater workout-regimen adaptation responses, such as increased strength and/or muscle mass. However, there do not appear to be any human studies on pure 4-ILE.

The recent introduction of unique fenugreek extracts claiming to contain 4-ILE (Promilin, for example) will possibly spur more research on the sweet promise of this bitter seed.

A tart way to shrink tumors
Citrus pectin is found in the white, fleshy part of limes, lemons, oranges and grapefruit. It is a soluble fibre composed of mostly non-digestible carbohydrates. However, when citrus pectin is chemically modified by exposing it to alkaline conditions, it reveals a new facet of activity. The new identity, modified citrus pectin (MCP), holds substantial promise for cancer therapy and the prevention of metastasis. MCP is a more water-soluble and well-absorbed fibre than its parent—unmodified pectin. However, MCP also helps prevent growing and spreading tumours, cutting off the lines of communication between healthy and cancer cells.7,8,9 This 'disconnection of the phone line' action of MCP manifests as potent anti-cancer activity in animals fed MCP.

A recent study with mice lacking a full immune system (no thymus gland) and injected with human breast cancer cells found MCP-enriched drinking water (at neutral pH, to reduce the acidic taste) substantially arrested tumour growth rates.8 Additionally, significantly fewer MCP mice had metastases to the lungs. Similar results were also found with human colon cancer cells implanted in mice. The researchers also showed that MCP inhibits angiogenesis, the process of new blood vessel formation, which is a critical step in the growth and spread of tumours. MCP undoes cancer cell growth apparently by binding to a carbohydrate-binding protein called galectin-3, which has an integral role in tumour processes.9 This 'ties up' the cellular communication system, resulting in reduced tumour invasiveness and aggressiveness.

To date, there appears to be only one human study testing MCP. In it, researchers found five of 23 colon cancer patients experienced stabilisation of tumour growth over a period of two to six months, and one patient showed tumour reduction.9

Anthony L. Almada, BSc, MSc, is the president and chief scientific officer of IMAGINutrition Inc ( and has been a co-investigator on more than 60 randomised controlled trials.


1. Sauvaire Y, et al. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 1998;47:206-10.

2. Petit P, et al. Insulin stimulating effect of an original amino acid, 4-hydroxyisoleucine, purified from fenugreek seeds. Diabetologia 1995;38:A101.

3. Broca C, et al. 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties. Am J Physiol 1999;277:E617-23.

4. Breil V, et al. Effect of 4-hydroxyisoleucine on insulin sensitivity in insulin resistant rats. Diabetologia 2001;44:A79.

5. Broca C, et al. 4-Hydroxyisoleucine improves glucose tolerance in normal and NIDDM animals. Diabetologia 1998;41:A239.

6. Fernandez-Alvarez J, et al. Could 4-hydroxyisoleucine be used as a hypoglycaemic agent in the treatment of type 2 diabetes mellitus? Diabetologia 1996;39:A234.

7. Pienta KJ, et al. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst 1995;87:348-53.

8. Nangia-Makker P, et al. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J Natl Cancer Inst 2002;94:1854-62.

9. Nangia-Makker P, et al. Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. Trends Mol Med 2002;8:187-92.

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