Hypoglycemia in Hereditary Fructose Intolerance

What are the specific reasons for hypoglycemia seen in hereditary fructose intolerance?

Hereditary fructose intolerance (HFI) an autosomal recessive disorder in which there is subnormal activity of the enzyme fructose 1-phosphate aldolase B (1;2). Largely found in the liver, the enzyme is needed for normal fructose metabolism for splitting fructose 1-phosphate to form dihydroacetone and glyceraldehyde (1).

Hypoglycemia after consumption of fructose (also sucrose or sorbitol) results because of the lack of maintenance of proper blood glucose levels by the liver (2). The fructose ingestion and the lack of aldolase B results in the accummulation of fructose 1-phosphate in cells, particularly in the liver (1). The accumulation leads to depletion of Pi, which in turn keeps mitochondria in hepatocytes from producing ATP causing cell damage, and inhibition of glycogenolysis and, thus, guconeogenesis (1;2).

HFI often goes unrecognized and is life-threatening due to hypoglycemia along with possible liver and renal failure (3;4). Many of patients afflicted with the disorder have a noted distaste for sweet foods due to having suffered symptoms early in life such as vomiting and abdominal pain (2-4). The cure for HFI is exclusion of sources of fructose from the diet (1-4).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002, pp 597 & 643.
2. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
3. Yasawy MI, Folsch UR, Schmidt WE, Schwend M. Adult hereditary fructose intolerance. World J Gastroenterol 2009;15:2412-3.
4. Cox TM. Hereditary fructose intolerance. Baillieres Clin Gastroenterol 1990;4:61-78.

Niacin and Hyperlipidemia

NIACIN FOR HIGH CHOLESTEROL
The recommended daily intake for niacin, or vitamin B3, is only 14 mg for women and 16 mg for men with a tolerable upper intake level of 35mg (1). Nutrition professionals should also be aware that niacin, as nicotinic acid (not nicotinamide), has also been used in much larger doses—up to 6 g per day—for decades as a treatment for hyperlipidemia (1). Note that nicotinic acid is available as a dietary supplement.

Use as a Drug
High-dose niacin, in fact, was the first-ever lipid-modifying drug treatment. It helps increase HDL cholesterol while lowering total serum cholesterol, triglycerides and LDL cholesterol (2). After initial discovery in the 1950s and research in the ‘70s, it was found that niacin helped prevent myocardial infarction and reduced risk of death from myocardial infarction when used in doses of 3 g daily (2;3).

The mechanism of high-dose nicotinic acid is broad and unique. It inhibits lipolysis in adipose tissue decreasing free fatty plasma levels within minutes (1;2). Within a few hours it inhibits the liver’s synthesis of triglycerides reducing overall triglycerides in plasma (1;2). And, although it’s unclear just how, after only a few days it lowers LDL and increases HDL cholesterol (1;2).

Unpleasant Side Effects
Although an effective treatment and cost effective, the unpleasant side effects of high-dose niacin have kept many patients from adopting niacin as a regular drug treatment (2). By the 1980s, statins were on the market and greater in popularity (2). Still, niacin continues to present potential.

The main side effect is vasodilation, which includes flushing and redness like a temporary sunburn-like sensation (1;2). This is harmless, but bothersome (2). It is mediated partly by release of histamine; thus, an aspirin or COX inhibitors can reduce the response (1;2).

Precautions
Other side effects can include gastrointestinal problems like heartburn, elevated plasma glucose concentration, and hyperuricemia that can lead to gout since niacin competes with uric acid for excretion (1). Most worrisome is possible hepatotoxicity, which can go as far as obstructing bile flow, hepatitis or liver failure (1).

Newer forms of extended-release niacin, such as Niaspan from Abbot, are reported to have fewer side effects and no hepatotoxicity (2). This is significant for re-establishing niacin as the preferred, cost-effective treatment in comparison to other drugs. Newer studies are now researching niacin’s effectiveness in comparison to or in combination with other lipid- and cholesterol-lowering drugs (3). See "Research Summary and Critique" below.

Niacin is available in immediate-release (IR), sustained-release (SR), and extended-release (ER) (Niaspan) (4). They all differ in effectiveness, side effects and safety. Flushing is seen most with IR, hepatotoxicity is mostly noted with SR (4). The hepatotoxicity has to do with absorption rate (4). ER apparently allows absorption to be "intermediate" in comparison to IR and SR (4). In conclusion, avoid SR niacin!

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

2. E T Bodor and S Offermanns. Nicotinic acid: an old drug with a promising future. Br J Pharmacol. 2008 March; 153(S1): S68–S75. Published online 2007 November 26. doi: 10.1038/sj.bjp.0707528. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18037924.

3. Guyton JR, Blazing MA, Hagar J, Kashyap ML, Knopp RH, McKenney JM, Nash DT, Nash SD. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Arch Intern Med. 2000 Apr 24;160(8):1177-84. Available at: http://archinte.ama-assn.org/cgi/content/full/160/8/1177#TABLEIOI90276T3

4. Pieper JA. Understanding niacin formulations. Am J Manag Care 2002;8:S308-S314.


RESEARCH SUMMARY AND CRITIQUE
One randomized, double-blind human clinical study in 2000 made a direct comparison using Niaspan and gemfibrozil.

Full reference: Guyton JR, Blazing MA, Hagar J, Kashyap ML, Knopp RH, McKenney JM, Nash DT, Nash SD. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Arch Intern Med. 2000 Apr 24;160(8):1177-84. Available at: http://archinte.ama-assn.org/cgi/content/full/160/8/1177#TABLEIOI90276T3

Purpose of Study: To compare effects of Niaspan with gemfibrozil, a lipid-lowering drug from a class called fibrates. Commercially, gemfibrozil goes by names of Lopid, Jezil and Gen-Fibro.

Type of study: Randomized, double-blind human clinical study.

Methods: Patients exhibiting factors for hypercholesterolemia and atherosclerosis were given Niaspan at doses increased sequentially from 1g to 2 g before bedtime and 80 or gemfibrozil at 600 mg given twice daily. Of 173 patients, 72 of 88 given Niaspan and 68 of 85 given gemfibrozil completed the study.

Percentage change from baseline was provided through analysis of blood samples collected after 12-hour fasts. They provided measurements for total cholesterol, HDL cholesterol, LDL cholesterol, lipoprotein levels, total triglycerides and fibrinogen levels.

Exclusions included most diabetics (not with normal-range fasting glucose), patients on blood thinners, patients with active gout as well as those with other serious illnesses and/or abnormalities.

The patients were men and women between ages 21 and 75 years. All were counseled by a National Cholesterol Education Program.

Results Summary: Niaspan increased HDL cholesterol twice as much as gemfibrozil and had better results in improving LDL cholesterol while lowering levels of fibrinogen (protein involved in clotting). The gemfibrozil had greater effects at lowering triglycerides, but increased LDL cholesterol.

Much more Niaspan flushing responses (78% compared to 10%) were observed in comparison to gemfibrozil; however, dyspepsia was observed more often in patients taking gemfibrozil.

Critique of Research Design: The study was well-designed and included appropriate measurements to determine biological response to treatment. The exclusions were appropriate in nature. The support of a pharmaceutical company for the study hinted at a natural bias that could be noted since there was no discussion given by the authors of this study regarding possible confounding variables. The flushing responses clearly indicate that the patients would have known what they were taking, which may have affected results. Also, dietary factors were not noted in the study. There was conversation seeming out of place about the possible use of both drugs for complementary treatment, which would need further research.

Nutritional Implications and Implications for Future Study: Nutrition professionals should have a thorough understanding of its uses and possible side effects when used as a drug for hypercholesterolemia. Because niacin is a vitamin found in many foods, further research should also review the potential role of diet along with niacin treatment.

Bs for Stress and Energy

B-complex supplement products are popular commodities, often marketed for "stress" or "energy." Is there scientific justification for these claims? Why should anyone choose a B-complex supplement as opposed to either broader multivitamin-mineral supplements or narrower single B-vitamin supplements?

You might remember in the early ‘90s when a neuropathy epidemic broke out in Cuba among unsuspecting tobacco growers. They complained of burning sensations in their feet, pain in their arms and legs, frequent urination, blurred vision, weight loss, sensitivity to sunlight, and, well, lots of stress and fatigue (1). After assessing their diets it was discovered they were deficient in B complex vitamins and the amount of alcohol they drank daily contributed to loss of the little Bs they had (1).

The tobacco growers may have not known that B vitamins play essential roles in the health of their bodies relating to energy metabolism and stress, but let’s be sure we do.

Energy

For generating ATP energy in the body, B vitamins act mainly in synergy. Specifically, the vitamins thiamin, riboflavin, niacin and pantothenic acid are all needed to act as co enzymes in the formation of a multi-enzyme complex known as pyruvate dehydrogenase complex (2). Pyruvate dehydrogenase complex is essential for the oxidative decarboxylation of pyruvate to form acetyl CoA, which feeds into the citric acid cycle (2). Take any of the B vitamins away and cellular respiration is no more.

Further, niacin either as nicotinic acid and nicotinamide is necessary for use in the forms of NAD, nicotinamide adenine dinucleotide, and, with a phosphate at the end, NADP. NAD and NADP act as coenzymes for about 200 enzymes (oxidation-reduction reactions). But a major role of NAD in its reduced form as NADH is to shuttle electrons through the electron transport chain creating ATP energy (2). Apart from joining the other Bs in oxidative decarboxylation of pyruvate, NAD and NADH also act as coenzymes in glycolysis, oxidation of acetyl CoA, beta-oxidation of fatty acids and oxidation of ethanol for energy (2).

Riboflavin is needed for its coenzyme derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Like NAD and NADP, FMN and FAD act as coenzymes in oxidative-reduciton reactions for many reactions (2). Apart from use in pyruvate dehydrogenase complex in which FAD acts as an electron carrier, FAD also is needed for the flavoprotein succinate dehydrogenase to remove electrons from succinate to form fumarate (2). Then electrons are passed into electron transport chain by coenzyme Q (2).

Biotin’s role in energy has to do with its coenzyme role in enzymes. Two regulatory enzymes are dependent on biotin: pyruvate carboxylase, regulator of carboxylation of pyruvate, acetyl CoA carboxylase, regulator of fatty acid synthesis (2). Two enzymes need biotin for catabolism of amino acids need biotin, propionyl CoA carboxylase and beta-methylcrotnonyl CoA carboxylase (2). Lack of biotin will produce lethargy, depression, hallucinations and muscle pain (2).

Cobalamin once converted to adenosylcobalamin can act along with biotin in a energy metabolism in which it acts to help convert methylmalonyl CoA mutase convert L-methylmalonyl CoA to succinyl CoA (2). L-methylmalonyl CoA is produced from D-methylmalonyl CoA, which was produced from propionyl CoA that arose from from oxidation of amino acids and odd-chain fatty acids from the biotin-dependent reaction (2).

Pantothenic acid, aside its role in pyruvate dehydrogenase complex as a component of CoA, also acts as a component of CoA in lipid metabolism such as synthesis of ketone bodies and fatty acids (2). Although deficiency is unlikely—it’s ubiquitous in food—among the symptoms would be fatigue and weakness (2). Its deficiency is characterized by numbness in the toes called “burning feet syndrome” of which was no doubt suffered by the Cuban tobacco farmers who lacked it (1;2).

Stress

Some examples of stress were given above, but stress help from B vitamins is largely the work of thiamin. Thiamin, in this case not as a coenzyme, may activate ion transport in nerve membranes as well as regulating sodium channels and acetylcholine receptors in nerve impulse transmissions (2). A thiamin deficiency produces beriberi (beri meaning “weakness”) and one of its first signs is anorexia and weight loss, then neurological symptoms of confusion and apathy in what can only end up as irritability (2).

Riboflavin has its role in stress too—and I’m using the word “stress” as a very wide-reaching general term. FAD-dependent monomaine oxidase is required by neurotransmitters such as dopamine (2). Regeneration of the antioxidant glutathione—which supports against oxidative stress—is dependent also on FAD-dependent glutathione reductase (2).

Without niacin life could be especially stressful due to pellagra, which comes with its four Ds: dermatitis, dementia, diarrhea and death (2). But the B vitamin’s more direct role is in reducing oxidative stress via regeneration of glutathione, vitamin C and thioredoxin (2).

Finally, the pernicious anemia from a deficiency or poor absorption of cobalamin would lead to neuropathy of which is characterized by demyelination of the nerves—painfully stressful indeed (2).

Supplementation

OK, so we know the roles of B vitamins as related to energy and stress. We definitely need them. The question remains, however, whether or not a normally healthy person should supplement? Plus, will taking more of B-complex act as an ergogenic aid such as for athletes?

The studies aren’t showing much promise. There is indication that exercise causes greater need for B-complex supplements (5). Athletes should continue to take them. But, despite widespread use of B-complex supplements among athletes even in massive doses, they should not be expected to increase actual performance unless a deficiency was in existence beforehand (3;4).

Those of us who aren’t athletes would benefit from B-complex vitamins simply to help us avoid deficiency and because of their lack of toxicity. But don’t expect huge increases in “energy” or reductions of “stress” unless you are deficient. Deficiency can happen if you're malnourished, abuse alcohol, are a strict vegetarian (B12 or riboflavin) or if you have a disorder such as pernicious anemia (B12 deficiency) (2).

Reference List

1. Arnaud J, Fleites-Mestre P, Chassagne M et al. Vitamin B intake and status in healthy Havanan men, 2 years after the Cuban neuropathy epidemic. Br J Nutr 2001;85:741-8.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
3. Williams MH. Vitamin supplementation and athletic performance. Int J Vitam Nutr Res Suppl 1989;30:163-91.
4. Williams MH. Vitamin and mineral supplements to athletes: do they help? Clin Sports Med 1984;3:623-37.
5. Woolf K, Manore MM. B-vitamins and exercise: does exercise alter requirements? Int J Sport Nutr Exerc Metab 2006;16:453-84.

Vitamin E

Vitamin E refers to eight compounds (vitamers: tocopherols and tocotrienols) and is found in both plants and animal foods (1). The most studied natural source of vitamin E is alpha-tocopherol because of its prevention of lipoprotein oxidation and inhibition of platelet aggregation, which suggests prevention of cardiovascular disease (1).

Alpha-tocopherol is the only one with biological activity and offers the most protection against oxidative stress through its oxygen-quenching capacity (2). The natural and most active form is designated by its steroisomer RRR alpha-tocopherol and continues to be found on supplement labels as d-alpha tocopherol (2).

Beta-tocopherol also exhibits oxygen-quenching capacity albeit not as much as alpha-tocopherol and its abilities are followed by gamma- and delta-tocopherol (2). The tocotrienols may not exhibit significant antioxidant role, but have another role in which they reduce plasma cholesterol concentration (2).

A recently discovered natural form of vitamin E is alpha-tocopheryl phosphate found to be ubiquitous in tissues of animals and plants (3). Its role is not yet clear.
Supplementation with vitamin E is widely popular for taking guesswork out of how to get enough of this seemingly non-toxic vitamin for cardiovascular health (1;4). Newer research on vitamin E, however, is showing that it may be possible that people are taking too much (1;5).

Clinical trials on alpha-tocopherol have mostly found negative results including possible increased adverse effects on those with high blood pressure and increased risk of death in those with cardiovascular disease (1).

Until further is known about the most appropriate amount to take for reduced risk of disease, the Recommended Dietary Allowance for vitamin E continues to be 15 mg daily, based on the natural form of alpha-tocopherol, and is still considered one of the least toxic vitamins (2).

Reference List

1. Clarke MW, Burnett JR, Croft KD. Vitamin E in human health and disease. Crit Rev Clin Lab Sci 2008;45:417-50.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
3. Gianello R, Libinaki R, Azzi A et al. Alpha-tocopheryl phosphate: a novel, natural form of vitamin E. Free Radic Biol Med 2005;39:970-6.
4. Gutierrez AD, de Serna DG, Robinson I, Schade DS. The response of gamma vitamin E to varying dosages of alpha vitamin E plus vitamin C. Metabolism 2009;58:469-78.
5. Bell SJ, Grochoski GT. How safe is vitamin E supplementation? Crit Rev Food Sci Nutr 2008;48:760-74.

Bugs Bunny diet

Could it be that when Bugs Bunny chose his special diet of carrots because he knew that the discovery of vitamin A in 1915 found it was an essential growth factor in animals (1)? Maybe he knew that vitamin A kept his skin healthy under all that fur (1). Or, more likely, that vitamin A kept his eyes healthy for seeing underground (1).

Bugs can also celebrate that his enjoyment of carrots might keep him from later having to say, “What’s up doc?” This is because clinical evidence has led the U.S. Food and Drug Administration to approve a cancer health claim for a low-fat diet rich in fruits and vegetables when it includes vitamin A (1).

Vitamin A’s benefits are all appealing to humans too. But while vitamin A deficiency is not common in developed countries, a few are deficient not being regular eaters of foods high in vitamin A like carrots, sardines or liver (1).

How much should you get? What kind of vitamin A should you be getting? And, how do you know when you should supplement? Clinicians should be familiar with the differences of the various kinds of vitamin A because it would affect recommendations.

Vitamin A references any compound that can produce biological activity of all-trans retinol (1). These include preformed vitamin A retinoids (retinol, retinal, retinoic acid, retinyl esters and others) and provitamin A carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin) (1).

Absorption of vitamin A first requires digestion in which enzymes help free up vitamin A from proteins and fats (1). The vitamin A compounds then become solubilized into bile micelles to be transported and absorbed across the brush border membrane of the duodenum and jejunum (1).

The preformed vitamin A retinoids are absorbed easily (about 70-90 percent) as long as a meal includes sufficient fat (1). Provitamin A carotenoids are less absorbed ranging from less than 5 percent in raw foods and juices and up to 60 percent when cooked or taken purely in oil (1).

Retinoids, being lipid-soluble, are not as stable as carotenoids and can oxidize when exposed to light, oxygen, heat or some metals (2). But, again being lipid soluble, about 70-90 percent of the preformed vitamin A retinoids are absorbed (1).

In developing countries, vitamin A deficiency is not common (1). It generally occurs among children leading to increased mortality and infectious morbidity (1). The symptoms of vitamin A deficiency can include xerophthalmia (night blindness, Bitot’s spots, conjunctival abnormalities, corneal scarring and ulcerations), anorexia, retarded growth, karatinization of mucous cells (1).

The best measure of vitamin A from which to make recommendations is retinol activity equivalents (RAE) (1). For example, retinol 1 mcg is equal to RAE 1 mcg, beta-carotene 12 mcg is equal to RAE 1 mcg, and alpha-carotene or beta-cryptoxanthin 24mcg is equal to RAE 1 mcg (1). The requirements of vitamin A intake published by the Institute of Medicine’s Food and Nutrition Board published in 2001 that adult men should consume 625mcg RAE and women 500mcg RAE (1).The Recommended Dietary Allowance (RDA) is 900 and 700 mcg RAE for men and women (1).

Pregnant women have a higher RDA ranging from 770 and 1,300 mcg RAE (1)Smokers, however, should watch any increase because newer research shows vitamin A may increase risk for lung cancer rather than decrease it (1). The biochemical reasons for increasing lung cancer risk are not clear yet, but may have to do with break down products and mitochondriotoxicity (3).

Because main food labels still list vitamin A in the older International Units (IU), it’s important to point out that 1 IU vitamin A is equal to 0.3 mcg regtinal, 3.6 mcg beta-carotene and 7.2 mcg of alpha-carotene and beta-cryptoxanthin (1).

It is possible to get too much vitamin A. Hypervitaminosis A is a disorder that can lead to nausea, vomiting, double vision, headache, dizziness and skin problems (1).

The tolerable upper intake level for preformed vitamin A in adults is 3,000 mcg (1). Beta-carotene and the other provitamin A carotenoids do not have any known tolerable upper intake level (1). A tolerable upper intake level of beta-carotene levels in smokers has yet to be established (1).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Carlotti ME, Rossatto V, Gallarate M, Trotta M, Debernardi F. Vitamin A palmitate photostability and stability over time. J Cosmet Sci 2004;55:233-52.
3. Siems W, Salerno C, Crifo C, Sommerburg O, Wiswedel I. Beta-carotene degradation products - formation, toxicity and prevention of toxicity. Forum Nutr 2009;61:75-86.

Antioxidants - Comparing Apples to Oranges

Which will keep the doctor way? The orange contains about 10 times more vitamin C, which is an essential antioxidant for many complex roles in the human body (1). On the other hand, the apple contains quercetin, which has been shown to have a higher antioxidant capacity than vitamin C, thus, potentially offering better protect against free radicals (2;3). Clearly these antioxidants are not equal.

Free radicals are atoms or molecules that have one or more unpaired electrons. These are mainly result of the mitochondria leaking electrons that bind to oxygen; however, there are a variety of other free radicals from exposure to smog, ozone, drugs, and drugs (1).

Because “oxidative stress” is thought to be associated with many diseases including cancer, antioxidant nutrients are frequently evaluated for ability to neutralize free radicals, particularly the oxygen-centered radicals: superoxide, hydroxyl and peroxyl radicals (1).

While antioxidants help decrease neutralize free radicals, they themselves become free radicals although—in some cases such as vitamin E, C, ubiquinol and glutathione—regeneration pathways in the body often help them function over again (1). The regeneration process is key for optimal defense against oxidative stress and so is receiving enough of different kind of antioxidants (1).

As science continues to discover more and more, high-antioxidant foods continue to grown in the marketplace. Walk down the isle of any health food store and you’re sure to spot the latest and greatest—pomegranate, blueberry, acai berry, green tea. What makes one food greater than another?

These compete by antioxidant capacity including measures of oxygen radical absorption Capacity (ORAC) (4;5). Each ORAC unit indicates greater antioxidant protection—the higher the score, the more “super” the food (5). Another test more relevant biologically is cellular antioxidant activity (CAA), performed on cell cultures, which has found quercetin, pomegranate and berries clear favorites for decreasing oxidative stress (6). Antioxidant capacity can also be helpful to determine one fruit with another of the same fruit. For example, organically grown fruit and vegetables often have a higher ORAC score indicating greater content of fruit (7).

Should consumers rely strictly on ORAC or CAA tests for making food choices? The answer is, no. While single antioxidants may have unique functions that may link them to reduced risk of disease, such as vitamin C and heart disease (1), quercetin and liver cancer (8), no single antioxidant or antioxidant complex has appeared yet to decreases oxidative stress enough overall to reduce risk of all diseases (1).

As discussed above, however, antioxidants often work with each other synergistically in the body. Thus, for superior nutrition, adopt the “color code”: five to nine servings daily of fruits and vegetables of different colors provides the reds, red-purples, oranges, yellows, and greens for your body daily and is in line the National Cancer Institute and American Institute (9). Until more is known about antioxidants, the color code offers the the best guideline for health and prevention of disease (1).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Wolfe KL, Liu RH. Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements. J Agric Food Chem 2007;55:8896-907.
3. Kim DO, Lee KW, Lee HJ, Lee CY. Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J Agric Food Chem 2002;50:3713-7.
4. Kohri S, Fujii H, Oowada S et al. An oxygen radical absorbance capacity-like assay that directly quantifies the antioxidant's scavenging capacity against AAPH-derived free radicals. Anal Biochem 2009;386:167-71.
5. Cao G, Alessio HM, Cutler RG. Oxygen-radical absorbance capacity assay for antioxidants. Free Radic Biol Med 1993;14:303-11.
6. Wolfe KL, Kang X, He X, Dong M, Zhang Q, Liu RH. Cellular antioxidant activity of common fruits. J Agric Food Chem 2008;56:8418-26.
7. Di RL, Di PD, Bigioni M et al. Is antioxidant plasma status in humans a consequence of the antioxidant food content influence? Eur Rev Med Pharmacol Sci 2007;11:185-92.
8. Seufi AM, Ibrahim SS, Elmaghraby TK, Hafez EE. Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences. J Exp Clin Cancer Res 2009;28:80.
9. Heber D, Bowerman S. Applying science to changing dietary patterns. J Nutr 2001;131:3078S-81S.

What is the biochemical reason why bile secretion is important for health?

Micelles are made up of amphipathic compounds such as bile acids, fatty acids and monoacylglycerols that interact leaving a relatively stable hydrophilic surface and hydrophobic interior (1). They form at certain temperature ranges when a mixture of lipids is present in concentrated amounts (1). Fatty acid and phospholipid micelles are spherical, but pure bile acid micelles are sandwich-shaped rectangles (1p1062).

During lipid digestion after hydrolysis of triacylglycerols by lipases, it’s up to the bile acid sandwiches to solubilize the spheres, thereby forming “mixed” micelles that appear not unlike rods (1p1062). These rods become longer as more lipids (including limited cholesterol) are solubilized (1p1062). The bile acid micelles form at concentrations of 2-5 mM and at pH values above pK, meaning in equilibrium with other micelles in solution (1p1061-2).

From the lumen, the micelles then transfer the lipids to the mucosal surface for absorption by diffusion (1p1063). Lipid-soluble vitamins A, D, E, and K are also transported within the micelles (1p1065). The delivery is dependent on bile acid micelles increasing effective concentration to create solute flux across the unstirred fluid layer (1p1063). Without bile acids, the absorption of triacylglycerols and the lipid-soluble vitamins would be reduced drastically (1p1063).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.