Biochemistry of Metabolic Syndrome

Connecting the biochemical dots that lead to atherosclerosis is what is best attempted by the term metabolic syndrome (MS) (1). The term, of which is still under controversy, is used as a predictor of cardiovascular disease and type 2 diabetes mellitus (2-4).

MS can begin with abdominal obesity (MS dot 1), a consequence of overeating and a sedentary lifestyle (1;5). The additional adipose tissue can then reduce affinity of insulin receptors and/or create abnormal post-receptor responses resulting in insulin resistance (MS dot 2) (1).

Once insulin resistance overwhelms capacity to produce insulin to overcome it, then type 2 diabetes mellitus (T2DM) ensues (1). T2DM is accompanied by hyperglycemia and often by hyperlipidemia (MS dot 3) (1). The hyperlipidemia results because VLDL and chylomicrons are not cleared by the enzyme lipoprotein lipase of which is dependent on insulin (1). The high levels of free fatty acids then impair insulin action further (1). Plus, new research suggests that reduced secreition of adiponectin along with tumor necrosis factor alpha (TNFa) and a protein called resistin act to impair insulin receptor function (1). Poorly controlled glucose levels is then found along with hyperinsulinemia in cases (1).

Finally, the insulin resistance and hyperinsulinemia can stimulate salt reabsorption in the kidneys causing hypertension (MS dot 4) (5). Hypertension, or elevated blood pressure, and its force on artery walls makes them vulnerable to plaque build-up and narrowing that can ultimately lead to hardening of the arteries or atherosclerosis (6).

Clinically, the knowledge of progressing events in MS is what allows it to serve a valid purpose with patients (5;7). A doctor or nutritionist, for example, can use MS awareness to predict future risk factors and assist in treating obese patients with lower-calorie diet and other methods.

Reference List
1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Lau DC. Metabolic syndrome: perception or reality? Curr Atheroscler Rep 2009;11:264-71.
3. Lien LF, Guyton JR. Metabolic syndrome. Dermatol Ther 2008;21:362-75.
4. Gallagher EJ, LeRoith D, Karnieli E. The metabolic syndrome--from insulin resistance to obesity and diabetes. Endocrinol Metab Clin North Am 2008;37:559-79, vii.
5. Ren J, Kelley RO. Cardiac health in women with metabolic syndrome: clinical aspects and pathophysiology. Obesity (Silver Spring) 2009;17:1114-23.
6. Takeuchi K. [Hypertension and metabolic syndrome/lifestyle diseases]. Rinsho Byori 2007;55:452-6.
7. de ZD, Bakker SJ. Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease? Nat Clin Pract Cardiovasc Med 2008;5 Suppl 1:S10-S14.

Glycosylated Hemoglobin to Detect Diabetes

Glycosylated hemoglobin forms when prolonged hyperglycemia leads to glucose in the blood not used for energy to attach itself to hemoglobin (1;2). The reaction does not require an enzyme, but occurs spontaneously (1).

The concentration of glycosylated hemoglobin determined by an assay can be used to determine the status of a diabetic patient and effectiveness of treatment (1;2). The glycosylated hemoglobin assay has been found to be a more effective tests than others such as the oral glucose tolerance test for the detection of diabetes (3).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002, pp893-4.
2. Diabetes and Hormone Center of the Pacific. Glycosylated hemoglobin testing. Available at: http://www.endocrinologist.com/Hemoglobin.htm
3. Dods RF, Bolmey C. Glycosylated Hemoglobin Assay and Oral Glucose Tolerance Test Compared for Detection of Diabetes Mellitus. Clin Chem 25/5, 764-768, 1979. Available at: http://www.clinchem.org/cgi/reprint/25/5/764

Metabolic Syndrome and Physicians

Despite controversy over the current definition of "metabolic syndrome", physicians are using it as a useful clinical tool. It can be used to help with counseling patients and to recommend treatments.

Metabolic syndrome is currently defined as a combination of several risk factors that ultimately lead to diabetes and cardiovascular disease. They include obesity, hypercholesterolemia, hyperlipidemia, hypertension, insulin resistance and inflamation (1).

Each of the several risk factors that makes up metabolic syndrome requires varying treatments, so physicians may find that lumping them together is not useful. In fact, controversy exists on if the term "metabolic syndrome" is even defined correctly (1).

But a 2007 Mayo Clinic meta-analysis found that metabolic syndrome is beginning to find development as a useful clinical tool (2). The review focused on heart disease factors and found that metabolic syndrome increased risk strongly (2).

Reference List

1. Cheng AY, Leiter LA. Metabolic syndrome under fire: weighing in on the truth. Can J Cardiol 2006;22:379-82.
2. Gami AS, Witt BJ, Howard DE et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403-14.

Personal magnesium intake

These are the foods I eat on a daily basis with highest magnesium intake:

Mixed Nuts - 308 mg per cup
Spinach - 150mg per cup
Yerba Mate - 90mg per cup
Chocolate Soymilk - 39mg per cup
Coffee (espresso) - 96mg per 4 oz

Total magnesium: 683mg

Luckily I'm meeting my recommended intake of 400mg per day.

Check your intake here: http://www.nal.usda.gov/fnic/foodcomp/search/

Is High Phosphorus Intake in the U.S. Diet Hazardous?

Controversy arises as to whether or not a high dietary intake of phosphorus is hazardous to health because in the U.S. the typical diet tends to be high in phosphorus and low in calcium (1). But although the need for increasing calcium for bone health has been clearly established, reducing phosphorus to re-balance the calcium:phosphorus ratio has not been shown to have any additional benefits (1;2).

Serum phosphate levels, for example, when high can reduce vitamin D formation in kidneys reducing serum calcium (2). But high phosphorus also appears to reduce urinary calcium indicating a reversal of the prior detriment (2). In addition, the kidney is effective in maintaining normal phosphorus balance by increasing excretion of phosphorus when necessary (1).

At this time no research including at least one controlled trial has not found any adverse effect from a diet high in phosphorus at levels common in the U.S. (1;2). The exception is in those with impaired excretion such as those with kidney dysfunction (2).

It is worth noting that because calcium interferes with phosphorus absorption, a higher calcium diet would lower phosphorus intake naturally (1). And when intake of phosphorus is in the form of phytate—which is plentiful in grains, legumes and nuts—it just might be detrimental because phytate can interfere with absorption of minerals such as calcium (1).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Linus Pauling Institute. Phosphorus. Micronutrient Information Center. Available at: http://lpi.oregonstate.edu/infocenter/minerals/phosphorus/

Calcium with or without vitamin D

Criteria for recommending calcium to a patient should not go without considering a patient’s vitamin D status. Vitamin D status is critical for improving intestinal absorption, for maintaining calcium homeostasis, for promoting reabsorption of calcium in the kidney and is involved in bone mineralization (1;2).

Calcium supplementation along with vitamin D has been subject of at least two randomized controlled trials in Australia. The first performed on 300 elderly women (77+/- 4.6 years) found no short-term benefit as to improving absorption or promoting bone health (3). But another, longer randomized controlled trial evaluated the effects of calcium with or without vitamin D over five years (4). The researchers studied hip bone mineral density and bone turnover in elderly women (ages 70-80) in a sunny climate (4).

Thus, while short-term benefits weren’t found, long-term benefits were, which where likely produced by reduced bone turnover rate over time (3;4). In response to the studies and other research, the Australian and New Zealand Bone and Mineral Society and Osteporosis Australia issued a joint statement explaining that while calcium intake above previously established recommended levels wasn’t likely to help prevent fractures in elderly men and women, the addition of vitamin D in supplements was supported by the evidence (5).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Cashman KD. Calcium and vitamin D. Novartis Found Symp 2007;282:123-38.
3. Zhu K, Bruce D, Austin N, Devine A, Ebeling PR, Prince RL. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Miner Res 2008;23:1343-8.
4. Zhu K, Devine A, Dick IM, Wilson SG, Prince RL. Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. J Clin Endocrinol Metab 2008;93:743-9.
5. Sanders KM, Nowson CA, Kotowicz MA, Briffa K, Devine A, Reid IR. Calcium and bone health: position statement for the Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia and the Endocrine Society of Australia. Med J Aust 2009;190:316-20.

High-magnesium diet to beat colorectal cancer

At least three cohort studies have been published relating to the possible role of magnesium in reducing risk of colorectal cancer in women.

The first was prospective study from Sweden and reported in JAMA in which researchers found a reduced occurrence of colorectal cancer in women who had a higher dietary intake of magnesium (1).

Hanging on the coat-tails of the Swedish study, U.S. researchers assessed magnesium status of a cohort in Iowa women and found the similar results of reduced risk (2).

The latest was from the Netherlands, which found a few differences from the first two, indicating that there was no significant trend of lowering risk of colorectal cancer except in populations of overweight subjects (3).

According to the latest study, the method by which magnesium has a protective effect is thought to be through decrease of insulin resistance (3). However, as suggested by the U.S. researchers, more observational studies are necessary and, perhaps, clinical trials to assess whether or not the results can be attributed to magnesium or other factors in relation to a high-magnesium diet (2).

Could fiber in green leafy vegetables be a variable? I imagine so.

Reference List
1. Larsson SC, Bergkvist L, Wolk A. Magnesium intake in relation to risk of colorectal cancer in women. JAMA 2005;293:86-9.
2. Folsom AR, Hong CP. Magnesium intake and reduced risk of colon cancer in a prospective study of women. Am J Epidemiol 2006;163:232-5.
3. van den Brandt PA, Smits KM, Goldbohm RA, Weijenberg MP. Magnesium intake and colorectal cancer risk in the Netherlands Cohort Study. Br J Cancer 2007;96:510-3.