Vitamin B12

Vitamin B12 or cyanocobalamin (not the active form of B12) is one of the most complex molecules required for the human body. B12 comes in different active varieties depending upon the reaction it catalyzes. Methylcobalamin catalyzes the conversion of homocysteine to methionine (by adding a methyl group) and adenosylcobalamin catalyzes the conversion of certain amino acids and three carbon fatty acid fragments into molecules funneled into energy production.

The term “cyano” comes from the method of purifying the vitamin (using cyanide) and cobalamin comes from the cobalt complexed in the center of the molecule. That cobalt ring is generically called a corrin ring. There is no cyanide in naturally occurring B12.

Vitamin B12 is made exclusively by bacteria and archaea, and can be found in organisms that have a symbiotic relationship with bacteria. Mollusks and organ meats such as liver are an excellent source of B12 as are muscle meats and varieties of other foods such as milk eggs and a host of seafoods including fish and shellfish. The requirements for B12 are fairly well known and the sources encompass primarily the organisms that harbor the vitamin producing bacteria. The Dietary Reference Intake for most adults is 2.4 µg per day. Most multivitamins contain 6µg.

What does B12 do? Again, B12 functions in methyl group transfers and has been found important in two human biochemical reactions:

1. Conversion of the amino acid Homocysteine to Methionine

2. Energy conversion in specific amino acids and odd chain fatty acid fragments


How humans evolved to require the water-soluble vitamin is still somewhat of a mystery and certainly beyond the scope of this blog. Needless to say, there are no artificial means of acquiring B12 outside of bacterial production. Why bacteria produce B12 in the first place is unknown as well. And human bacteria living lives in our colons do indeed produce B12 but it isn’t absorbed in appreciable quantities. Instead, it’s lost in the feces.

There are basically three ways to acquire B12 from the environment. One method is to consume soil containing bacteria which produce B12, a practice call “geophagia” and not good on the teeth. Another less savory method involves a practice called “coprophagia” where feces are consumed, presumably to acquire those lost vitamins and nutrients. Chimpanzee’s and numerous other animal species practice coprophagia, presumably to acquire the vitamin B12 content, but that’s speculation as well.

The final and most common approach to acquiring B12 is through the consumption of other animals, mollusks or algal species which themselves live in symbiosis with the bacteria that produce the B12.

Body Mass Index and Mortality

The ultimate measure of body shape and size, lifestyle and eating pattern is the answer to the following question: Will it (the eating pattern, lifestyle or body makeup) impact my overall risk of mortality? Health problems like the numbered stack I’ve listed below might arise, and there are well-know relationships between diet, fat distribution patterns and specific disease entities, but is there a healthy overweight category? Can someone have a BMI of 28, exercise regularly and still be considered healthy with a low risk of mortality? Maybe. Or maybe not.

By implication, the categories of BMI don’t lend any apparent wiggle room. That is to say, the overweight category, BMI 25 to 29.9, might seem innocent (since many if not the majority of the population now falls into this category) but is there a basis for stating that being overweight is unhealthy to the point of increasing the chance of mortality? More concrete than that, if my BMI is 26 am I at any more risk of death than some0ne with a BMI of 24?

Taking the liberal skeptics approach, if not, then all this wrangling to call more than half of all Westerners overweight and by implication, unhealthy, is an exercise in futility. A persons diet, body habitus, fat distribution and lifestyle may increase the risk of certain disease processes, but if it doesn’t impact mortality is it worth pursuing? Risking an argument that invokes quality of life questions and the economics of health care, if I'm overweight and I have a mortality rate the same as someone not overweight, don't preach weight loss to me.

According to widely held beliefs, when comparing those at ideal BMI (18.5 to 24.9), to obese individuals (BMI greater than 30) the risk of chronic medical problems attributed to that increase in weight is rather large. What follows is a number of health problems associated with a BMI greater than 30:
1. Diabetes
2. Hypertension
3. Heart disease
4. Stroke
5. Cancer
6. Decreased life expectancy
7. Sleep apnea

However, lets examine the most recent mortality data.

In a study[i] published in the Journal of the American Medical Association on April 20th 2005, Katherine Flegal and others examined data from the National Health and Nutrition Survey (NHANES) to report on excess mortality due to overweight and obesity. NHANES is a cross-section of Americans who are periodically interviewed and examined by representatives from the National Center for Health Statistics. The authors took data from NHANES I (1971-1975), NHANES II (1976-1980) and NHANES III (1988-1994) examining mortality data from each of the three groups sampled.

The first noteworthy trend found by comparing all three NHANES data sets, is a growing percent of individuals in America (and probably most of Western society) with a BMI greater than 35. In NHANES I the percent of individuals with a BMI greater than 35 was just 4.4%, but by NHANES III that number had risen to 8.3%.

The shocker in this study wasn’t that the excess mortality due to obesity wasn’t statistically significant (except for a BMI greater than or equal to 35); the jolt was that in the overweight category (BMI from 25 to 29.9) the actual excess mortality was less than zero. An excess mortality less than zero is interpreted to mean that relative to a normal BMI (18.5 to 24.9), those individuals categorized as overweight had a lower relative risk of mortality than those individuals in the normal BMI category.

In other words, the proposed health impact of overweight might not be considered unhealthy. And extending that thought, it might offer a benefit. According to this study, the excess weight appears to offer a very low risk of mortality to those overweight individuals, and might, in the current environment, offer an advantage. While the findings of a lower rate of death in the overweight category is tantamount to blasphemy, the study’s lead author hails from the National Center for Health Statistics, Centers for Disease Control and Prevention. More Later.

[i] Flegal et al., Excess Deaths Associated With Underweight, Overweight, and Obesity JAMA, April 20th 2005, Volume 293, pages 1861-67.

Body Mass Index Dissected

What follows is a little closer inspection of what BMI actually reflects. The formula once again is as follows:

Body Mass Index
Metric: = weight in Kilograms / (height in Meters)2
American: = weight in Pounds x 703/ (height in Inches)2

The following has been proposed to describe body mass classes:

Underweight: Less than 18.5
Normal Weight: 18.5 – 24.9
Overweight: 25 – 29.9
Obese: 30 or more

The mathematical model renders a number with the units of Kg/meter2 or mass per square meter. A natural question might be, wouldn’t it make more sense to measure mass per cubic meter? By that, cube the height and arrive at a mass per unit volume? It might seem to make sense but in correlation studies using a gold standard to measure percent body fat, the height squared actually correlates much better with percent body fat than the height cubed.

Again, the BMI is a mathematical model used to estimate CHANGES in % body fat. And population-wide that model does indeed hold true in nearly all cases. Most adults with an increase in BMI have a corresponding increase in % body fat. The running backs, competitive weight lifters and short distance sprinters with very low % body fat (but a high BMI, which gets higher with increases in muscle mass) make up only a very small fraction of the population and would be classified as outliers as they don't fit the mathematical model. The reason for that obviously relates to the greater density of muscle and lean tissue compared to adipose or fat tissue. With muscle weighing more than fat, a body builder adding muscle (building up for a competition) would have an increasing BMI with a decreasing % body fat!

Information BMI does not give:

1. Distribution of Body Fat
A high BMI as a number doesn’t necessarily describe percent body fat and absolutely doesn't define where on the body the fat might be distributed. Centrally, hips, thighs or evenly distributed over the entire body, the value give no information. And distribution as it turns out is probably more important than the absolute value of BMI.
2. Absolute Percent Lean Body Mass
Using the weightlifter with heavy muscle mass, as #1 above, the value of his/her BMI is meaningless as a reflection of percent body fat. And by corollary, gives no information about lean body mass.
3. Absolute Percent Body Fat
Although it’s an assumption that as an individuals BMI increases, the percent body fat increases, the value has no real relationship to percent body fat.

Body Mass Index Unraveled

Formulas to reflect body habitus or body makeup have in recent years defaulted to the calculation for body mass index (BMI). BMI has without question become the universal yardstick used by both clinical and research science to approximate percent body fat. The ultimate goal of any measure or calculation utilizing body weight or weight for height is to arrive at an estimate of the percent body fat. Inherent in the BMI classification system is a categorical assignment into one of the following based upon height and weight:

1. Underweight
2. Normal weight
3. Overweight
4. Obese.


The formula for BMI is simple and reflects mass per square meter:

Metric: BMI = weight in Kilograms / (height in meters)2
American: = weight in pounds x 703/ (height in inches)2

Lambert Adolphe Quetelet, a Belgian mathematician (1796-1874) developed concepts and definitions for determining the “average” man. In his quest to define the average man, he developed the Quetelet index which is the same formula for what we now call the BMI. The BMI has become one of the most utilized indices of “normal” weight for height. Other formulas, measures and scales of ideal body weight have been used by various organizations, but the BMI has yet to be replaced by a simpler measure reflecting the variation in weight for height.

Pierre Paul Broca, a French surgeon developed what was probably the first set of calculations to define ideal body weight in 1871. What his guidelines really amounted to was a rule of thumb:

Women: should weigh 100 lbs up to five feet in height, then five pounds for each additional inch.

Men: should weigh 110 lbs for five feet of stature and five additional pounds for each inch above five feet.”

Louis Dublin: The historical basis for ideal body weight in the United States began in 1942 when Louis Dublin, a statistician with the Metropolitan Life Insurance Company, categorized nearly 4 million subscribers according to frame size, height and weight. What he found was those who maintained an ideal body weight from the age of twenty-five into later years, had the best chance of survival. The Metropolitan Life Insurance Company revised those numbers in 1959 and again in 1983 allowing slightly higher average weights for respective heights to be categorized as normal. Planted in this line of thinking is what we call a “normal” weight individual or “weight appropriate” individual given their height.

Realize that this hypothetical normal weight range seems to be flexible as seen by the Metropolitan Life Insurance Company increasing the “normal” weight for height as the years progressed from the original 1942 study to the 1983 publication. Some argue the original ideal weight from the 1942 study should be considered the standard, while others are using the 1983 standards.

Absurd as it might seem, the concept of what constituted a healthy body was based upon what would earn Louis Dublin’s company the most money and keep people alive longer to pay more insurance premiums. Other factors that we now know affect life expectancy, like smoking and other lifestyle exposures, the quality of healthcare, the level of stress and other potential mitigating factors, weren’t factored in. As absurd as it might seem, in the initial studies by Dublin, smoking wasn’t considered a risk factor for early mortality—the association between smoking and lung cancer was not made until much later.

Many consider the Metropolitan Life Insurance Company’s appropriate weight for height given a frame size to be unusable, in part because the frame size was never really well defined by the company. However, the scale persists to this day and is still relied upon by a few organizations to risk-stratify individuals according to height, weight and frame size.

Omega-3 Fats: Concluding Remarks

There is much more to Omega-3 fats than this series of blogs lets on. I tend to focus on heart disease and the associations between foods and the risk of heart disease—basically because that’s my shtick. Omega-3 fats are proven effective in treating Hypertriglyceridemia and appear to be effective in preventing Sudden Cardiac Death. Its use in the primary prevention of heart disease is more controversial and hasn’t been shown to be definitively effective outside of other lifestyle factors and exposures.

I’ll briefly run through some of the suspected benefits of consuming Omega’s:

1. Alleviation of Psychiatric Illnesses: Bipolar disorder, Depression, ADHD, schizophrenia
2. Prevention of Macular Degeneration
3. Relapse rate of Chron’s Disease
4. Relapse rate of Relapsing Remitting Multiple Sclerosis
5. Lowered catecholamine levels
6. Treatment of Cancer anorexia
7. Alleviation of symptoms in Acute Pancreatitis

There are many more suspected benefits of Omega-3 fatty acids all of which seem to have a common thread. Omega-3 fatty acids produce inflammatory cytokines with a lower biologic/pharmacologic activity than cytokines produced from say Omega-6 fatty acids. Although this may not seem important, it represents one of the important reasons to consume Omega-3 fatty acids. Also, Omega-3 fatty acids become incorporated in phospholipids making up cell membranes and lipoproteins. That storage depot of fatty acids may be important in alleviating some of the disease entities listed above.

Sources of Omega-3 Fatty acids:
α-Linolenic Acid: Oils: Flaxseed oil, walnut oil, canola oil. Foods: Cauliflower, walnuts, spinach, pinto beans, tofu, and more.

EPA and DHA: Oils: Menhaden oil, cod liver oil, salmon oil. Foods: Salmon, oysters, mackerel, tuna, sea bass, shark, trout and many more sea food and fresh water fish species.

Amount to Take:
This is where things get a little sticky. Treatment of Hypertriglyceridemia is fairly straightforward and dose dependent; that is, consuming 4 grams a day is more effective at lowering the triglyceride count than consuming 2 grams a day.

If levels of DHA and EPA are your goal, to enable a reduction in inflammation from any of the above conditions in which Omega-3 fatty acids are suspected to help, the consumption of α-Linolenic Acid may or may not help. The problem is the conversion of α-Linolenic Acid to DHA and EPA is not reliable. In particular, it’s not reliable in men. In women, the conversion appears to depend upon global energy needs. In cases of severe caloric restriction, much of the α-Linolenic Acid may be metabolized for global energy needs. In a eucaloric state (a state where calories meet energy needs), the Linolenic Acid is effectively converted in DHA and EPA in women.

Dose to prevent Sudden Cardiac Death:
Sudden Cardiac Death is defined as death following a cardiac event, usually a myocardial infarction or heart attack. A number of observational studies have found that in those people either eating fatty fish or taking a supplement, the rate of death following a heart attack is much lower.

The optimal dose of daily fish or fish oil supplement to prevent sudden cardiac death after a heart attack, however, is a bit sketchy. There is some guidance based upon a dozen or so epidemiologic studies. But in reality, the precise information depends upon which study you bet the farm on. One salmon (or other fatty fish) dinner per week will supply about 1.5 grams of DHA and EPA which appears to be about the minimum intake to see a favorable outcome after a heart attack. The American Heart Association recommends healthy adults eat two fatty fish meals per week and include oils rich in α-linolenic acid like flaxseed oil, walnuts and canola oil.

Most supplements have a combined amount of DHA and EPA in the range of 500mg to 1 gram per gel capsule. Based upon the baseline benefit of one fatty fish meal per week, one capsule a day (1 gram combined of DHA and EPA) or even one capsule every other day would more than offset the minimum of one fish meal per week in preventing sudden death following a heart attack. The alternative is to eat the fatty fish once a week, which if cooked right, can be a far more rewarding experience than popping a fish oil capsule and burping up chicken-of-the-sea all morning.

Final Note on Omega-3 fats
I’ve noticed over the years when a food appears to offer some benefit, for example, eating fatty fish once a week, the elements of that beneficial food end up in supplements, soaps, skin creams, shampoo, and any of a number of other consumer products. Rubbing Omega-3’s on your skin might sound like a good thing, but there’s no evidence it impacts skin integrity, elasticity or longevity. Let there be no mystery regarding how I feel about food and product marketing. Marketing new products (especially new skin products) is tantamount to a criminal act until proven otherwise.