vitamin B12

The Analgesic Effects of B Vitamins

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It appears that high doses of vitamins B1, B6 and B12, administered separately or in combination, can alleviate acute pain by potentiating the analgesic effect of non-opioid analgesics such as diclofenac (an NSAID), sold under various trade names. These facts were published in a German paper. In addition, a randomized, double-blind, controlled clinical study was reported in 378 patients with lumbago. The term lumbago is a relatively old one and it is now often referred to as “back strain”.

The patients were divided into two groups, half of them receiving diclofenac together with very large doses of vitamins B1, B6 and B12. The other half received only diclofenac . The investigators concluded that the addition of the B vitamins did indeed enhance the analgesic effect of the drug. The primary mechanism for the anti-inflammatory, anti-pyretic and analgesic action of diclofenac is thought to be by a biochemical mechanism that is well known in the body and described in the paper.

When I read this, I became aware that the mechanism they were describing was the same mechanism that has been described for one of the actions of thiamine tetrahydrofurfuryl disulfide (TTFD, Allithiamine, Lipothiamine) a thiamine derivative that I have mentioned a number of times in posts on this website. When I further researched the mechanisms of action of diclofenac, I read that “diclofenac also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis”. Could it be that the drug has an effect on mitochondrial DNA in people using it to relieve their pain? If so, this would be a serious indictment on its use.

Mitochondrial DNA

We now have reason to believe that our mitochondria (cellular energy producing organelles) have evolved from an original bacterium millions of years ago, and we now know that they have their own genes. These genes, inherited only from the mother, are completely separate from the cellular genes that we inherit from both parents. They are vitally important in the function of mitochondria that are responsible for synthesizing ATP, the energy currency used by the body. The interesting thing is that mitochondrial DNA is like bacterial DNA, has a different conformation from that of cellular DNA, and could be expected to be sensitive to the “DNA related bacteriostatic activity” reported to be one of the effects of diclofenac.

Side Effects of Diclofenac

There are 50 side effects of diclofenac recorded online. It may surprise you to know that 20 of the symptoms reported as side effects are identical to those that are well known in relationship to the thiamine (vitamin B1) deficiency disease, beriberi. Since thiamine is vital to the normal function of mitochondria, perhaps it suggests why three members of the vitamin B complex enhance the analgesic effect of the drug by protecting the patient from harm. This would enable it to be used with reduced dose, thus obviating the possible appearance of side effects.

Side Effects of Pharmaceuticals

It is always wise for a patient who is taking a drug to know what the potential side effects are. With this story of diclofenac, I was reminded of a drug that was produced in the 1930s in order to stimulate weight reduction. The chemical name is dinitrophenol (DNP). The side effects were so severe and occasionally caused sudden death, so it was withdrawn in 1938. Its present use is in experimental research in animals because it inhibits mitochondrial function and enables the researcher to study energy metabolism. Believe it or not, DNP is still available for weight reduction. There is no doubt that it works but it certainly offends  the Hippocratic oath accepted by all physicians, “thou shalt do no harm”.

Genetic Susceptibility

We simply do not know the genetically determined susceptibility of an individual in the use of a foreign agent prescribed to relieve a given symptom. The body always recognizes a “foreigner” and sets about breaking it down and getting it out of the body as quickly as possible. If a vitamin is used in a much larger dose than merely replacing it as an essential nutrient, it may be thought of as a drug. This is really a new concept in medicine and has not yet reached the collective psyche of medical practice. Perhaps the body recognizes the huge dose, but uses what it needs and excretes the excess. The trouble with that is that the present concept is that vitamin replacement is thought to be confined to the tiny doses found in natural food that are required by a healthy individual. No thought has been given to the fact that a vitamin may have to be used in order to stimulate and restore the decayed effectiveness of the enzyme to which it must bind. It is as though the roles of the enzyme and the vitamin are reversed. In a sense, the enzyme becomes cofactor to its requisite vitamin rather than the normal enzyme/cofactor relationship.

Energy Metabolism is the Core Issue

What seems to be emerging from all this is that failure of energy metabolism, coupled with genetic risk and the imposition of individual life stresses, provides us with a new medical model for disease. Besides killing the “enemy”, the bacteria, viruses or cancer cells safely, the only real treatment possible is an educated use of nutritional components to coerce damaged cellular systems back into a state of functional efficiency. Healing takes energy and only the body knows how to do that. We should give it every possible assistance. There is much evidence that even cancer cells become maverick because of devious energy metabolism.

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The Hidden Heart Disease Risk Factor: High Homocysteine

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You may unknowingly have a ticking time bomb for heart disease flowing through your body. Right now. And you haven’t been told about it. Until now. Naturally produced in your body, a chemical substance called homocysteine often becomes elevated due to age, diet, and genetic disposition. If your homocysteine is high, you are at an increased risk of developing heart disease including heart attacks, coronary artery diseases, and strokes.

Staggering Mortality Rates

Heart disease is the number one cause of death worldwide. More than 17 million people—nine million of whom are women–die annually from heart disease.

In the United States heart disease ranks as the top killer of women. More than 500 American females die daily from heart disease. Furthermore, heart disease deaths in American women under the age of 55 continue to rise, according to a study published in the June 2013 issue of the journal Global Heart.

Why are so many people dying from heart disease? We have been educated to believe high blood pressure, high LDL cholesterol, and smoking are the primary causal culprits in causing heart disease. Physical inactivity, obesity, and excessive alcohol use also are attributed as risk factors for heart disease. But we hear little information about homocysteine as an independent factor for heart disease.

What is Homocysteine?

Homocysteine is an amino acid (a building block of protein) naturally produced in the body from a byproduct of another amino acid called methionine. Healthy amounts of homocysteine are vital in protein metabolism. However, homocysteine levels must be carefully balanced by adequate quantities of specific B vitamins.

Ideally, about half of homocysteine is recycled back into methionine (remethylation), and the other half is converted into a beneficial amino acid called cysteine (transsulfuration). This bifurcated process is dependent on specific B vitamins. Remethylation cannot occur without folate (vitamin B9) and vitamin B12. Transsulfuration cannot happen without vitamin B6. If these B vitamins are deficient, dangerous levels of homocysteine can accumulate in the body and damage the lining of the arteries, often causing heart disease.

Homocysteine Matters

In the late 1960s, Kilmer S. McCully, M.D., a young pathologist at Harvard University School of Medicine, reviewed a number of pathological findings of cases as far back as 1933 that involved young children with a genetic disorder who perished from atherosclerosis (hardening of the arteries). He discovered that elevated homocysteine damages arterial lining, causing arterosclerosis. Dr. McCully concluded that elevated homocysteine from a high animal-protein diet, more so than fats and cholesterol, was the primary cause of heart disease.

McCully subsequently published his ground-breaking conclusion in a 1969 issue of the American Journal of Pathology. By purporting such an unorthodox theory, he committed medical heresy.(1) Harvard denied him tenure, effectively firing him. Undeterred, he forged ahead, conducting research on homocysteine. He still practices medicine in the United States today.

Thanks to Dr. McCully’s tenacious efforts over the past four decades, a plethora of studies supporting his theory have been published. Landmark studies from the mid-1990s contributed to mainstream medicine’s eventual, yet delicate, embrace of the fact that high homocysteine is significant risk factor for heart disease. This research includes:

As part of the acclaimed Framingham Heart Study, researchers from Tufts University examined 418 men and 623 women, ages 67 to 96 years, to study their homocysteine blood plasma levels as well as their vitamin intake including folate, vitamin B12, and vitamin B6. The Tuft research team concluded that people with homocysteine levels greater than 11.4 µmol/L have a significant risk of having a heart attack. These findings were published in the February 2, 1995 edition of the New England Journal of Medicine.

The results of a study conducted by The European Concerted Action Project, a consortium of doctors and researchers from 19 medical centers in nine European countries, clinched the theory that Dr. McCully asserted almost two decades prior. By comparing 750 people under the age of 60 with blockages in their coronary arteries with 800 healthy persons also under 60 years old, the Project team determined that an elevated homocysteine score posed as great a risk as smoking or high cholesterol. Furthermore, people with the highest homocysteine levels had twice the risk of developing heart disease. Finally, the consortium discovered that those people who took folate, B12, and B6 supplements had a risk factor of about 66 percent less than those subjects who did not take the B vitamin supplements. The findings were published in the June 11, 1997 issue of the Journal of the American Medical Association.

What is a Healthy Homocysteine Level?

Homocysteine levels are easily evaluated by a simple test of blood plasma. Heath care practitioners can order a homocysteine test. But guess what? We are not routinely tested for homocysteine. In fact, I never had been tested for this important amino acid until I recently requested the test from my primary care physician. (Read on for my homocysteine score.)

To further exacerbate the issue of homocysteine evaluation, many clinical testing laboratories consider a healthy homocysteine value between 5 and up to 15 µmol/L. However, the upper limit of this range is highly misleading. A score of 6 µmol/L or less is optimal for homocysteine. Medical research has indicated that readings greater than 9 µmol/L indicate an increased risk for heart disease.

Reducing Homocysteine

The good news is that elevated homocysteine levels can be decreased by consuming adequate amounts of the B vitamins folate, B12, and B6. Although the daily dosage of these vitamins is dependent upon your homocysteine score, I offer general guidelines.

  • Foods rich in folate include wheat germ, lentils, sunflower seeds, spinach, broccoli, and romaine lettuce. If you are considering a supplement, note that “folate” is natural and “folic acid” is synthetic. Consider taking a daily 400-mcg folate capsule containing L-5-MTHF. (2)
  • The best food sources of vitamin B12 include sardines, oysters, cottage cheese, and tuna. When supplementing with B12, please ensure the B12 is methylcobalamin (methylB12). Many B12 supplements contain cyanocobalamin; yes, it contains a cyanide molecule. Consider taking 10,000 mcg daily of methylB12.
  • Fish and lean meats are excellent sources of vitamin B6 (pyridoxine). Consider taking a 25-mg B6 supplement.

You may recall that the amino acid methionine produces homocysteine. Too much methionine translates to excessive homocysteine. As animal protein is highly rich in methionine, it is wise to not overload animal protein consumption if the three major B vitamins are deficient.

Stunning Health Statistics

The scope of this article is limited to a brief discussion of elevated homocysteine as an independent risk factor for heart disease. However, I must tell you that homocysteine levels also affect the risk for developing a wide range of other serious medical conditions including cancer, diabetes, thyroid disorders, and Alzheimer’s disease. Let’s take a broad look at statistics.

Nestled in the spectacular western fjords of Norway, the University of Bergen houses one of the world’s leading homocysteine research centers. Since the 1990s, Bergen’s researchers have published dozens of papers reporting their homocysteine findings conducted during the University’s population-based Hordaland Homocysteine Study.

Having measured the homocysteine levels of 4,766 Norwegian men and women in their 60s a decade ago and then recorded those who lived and died, the researchers discovered that a 5-point decrease in homocysteine scores predicted, inter alia, a 50 percent reduced risk of death from cardiovascular disease as well as a 104 percent decreased risk of mortality from any disease or medical condition other than heart disease or cancer!

Are You Homocysteine Healthy?

It is not too early or too late to learn your homocysteine score. At the age of 60 and with a family history of heart disease, I requested a baseline homocysteine blood plasma test from my doctor. My score was an optimal 6µmol/L, a value that is most common in preteens! I attribute my homocysteine health score to feeding my body the folate, B12, and B6 it needs to maintain a balanced level of homocysteine.

Your level will not only predict your risk for heart and other serious diseases but it will help you understand how you can add energy and vitality to your life. Based on your homocysteine score, you can supplement with the necessary foods and/or dietary supplements that are readily available in retail and online outlets. And enjoy the benefits of being homocysteine healthy! I am glad than I am.

Footnote 1: Natural vitamins cannot be patented. Therefore, manufacturing and selling vitamins is far less lucrative than, for example, statins (cholesterol-lowing drugs.)

Footnote 2: The enzyme MTHFR (methylenetetrahydrofolate reductase) helps to facilitate the conversion process of remethylation.

Author’s Note: I wrote this overview to promote awareness of the potential heart disease risks associated with high homocysteine plasma levels. I briefly touched on the adverse effect of elevated homocysteine on the development of other serious medical conditions. If you are interested in learning more about homocysteine, I suggest reading: The H Factor Solution by James Braly, M.D. and Patrick Holford and/or The Homocysteine Revolution by Kilmer McCully, M.D.

Editor’s Note: Susan Rex Ryan is the author of the Mom’s Choice Award®-winning book Defend Your Life about the extensive health benefits of vitamin D. For additional information about vitamin D, check out our series of Sue’s articles, and visit her blog at smilinsuepubs.com.

This article was published previously on Hormones Matter in June 2014.

Copyright © 2014 by Susan Rex Ryan. All rights reserved.

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Maternal Vitamin B: From Periconception and Beyond

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Chandler Marrs

A wise midwife recently told me that in 1960’s the B vitamins were part and parcel of a healthy pregnancy, not just folate (vitamin B9), that we stress now, but the entire complex of B vitamins, including: thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (B7), folate (B9) and the cobalamins (vitamin B12). Thiamine (also referred to as thiamin) was viewed as critical for maternal and fetal health and used within the midwifery community to ensure not only a healthy pregnancy, but a healthy postpartum. In many non-industrialized regions, thiamine is still supplemented for maternal and fetal health and maternal thiamine deficiencies are still recognized as critical impediments to health. Not so in the Western, industrialized world. Here, most resources and education seem set on prenatal folate; so much that it is difficult to escape folic acid supplementation in everyday foods.  Despite heavy fortification and regular use of prenatal vitamins, we see increasing evidence of nutrient deficiencies in pregnant mamas and most especially, in their children. Some of these deficiencies are visibly obvious, as least to those who look, such as the increased incidence of neural tube defects in children of women who are low in vitamin B12, but sufficient, even abundant in folate or B9. While other deficits are not so obvious, at least not immediately.

Maternal vitamin B status is important to the pregnancy at hand but also for the child’s long term health, as many of the B vitamins are capable of activating or deactivating gene programs in the children. Maternal vitamin B deficiencies can induce long-term epigenetic changes in the children, and likely, grandchildren. Maternal (and probably paternal too) vitamin B deficiencies silence genes in their off-spring that significantly increase the risk of insulin resistance, high blood pressure and a host of metabolic disorders through adulthood. Nutrition, in addition to its vital role as a source of energy for our cells, is the guidepost for DNA activation and inactivation. The balance of nutrients tell our cells how to function or not function, as the case may be. This information is carried from parents to offspring, across generations. It is this genetic control derived from lifestyle and nutrients that forms the basis of health for our children, and so it becomes something as parents we must pay attention to.

The B Vitamins are Important for Mom’s Health

For the moms, latent deficiencies in core nutrients will become unmasked with the increasing energy demands of pregnancy as many nutrients are shuttled preferentially toward placental and fetal needs, depleting maternal stores. Following delivery, the demands of lactation will further deplete maternal nutrient status and depending upon the vitamin in question, adversely affect her health and/or her child’s health.  Reports link maternal thiamine deficiency to hyperemesis gravidarum – severe vomiting across the pregnancy, in some instances leading to a full blown Wernicke’s Encephalopathy. Maternal vitamin B12 deficiency is linked to an increased risk of developing preeclampsia, intra-uterine growth retardation, preterm labor, but also, low vitamin B12 puts mom at risk for developing a myriad of neurocognitive, neuromuscular and psychiatric symptoms associated with B12 deficiencies both during pregnancy and postpartum.

How Prevalent is Maternal Vitamin B Deficiency?

Since there are few reference ranges for vitamin status during pregnancy, with most ranges based upon non-pregnant women, and since much of the research in nutrition is conducted in non-industrialized, poorer countries, it is difficult to assess how many outwardly healthy, western women carry nutritional deficiencies into pregnancy and postpartum. A 2002 study reported the vitamin profile in 563 pregnant New Jersey women at different points across the pregnancy. They found a trend towards too much folate, riboflavin, biotin and pantothenate (vitamin B5) and too little niacin, thiamin, vitamins A, B6, B12, suggesting that prenatal vitamins neither appropriately nor sufficiently address maternal nutrient demands.

A study of healthy pregnant women in Spain found that 32-68% of the women tested were deficient in thiamine, riboflavin or pyridoxine. Interestingly, the severity of deficiency correlated with oral contraceptive use, specifically with the length of oral contraceptive washout period prior to becoming pregnant. That is, when the woman became pregnant shortly after stopping oral contraceptives, she was more likely to exhibit a vitamin deficiency than if she had to waited to become pregnant and allowed her body to readjust to the non-oral contraceptive state. Additionally, the researchers found that if the woman was deficient in one of these nutrients, she was more likely to be deficient in each of them. Although not measured in this study, we know from other studies that many medications, including oral contraceptives, metformin and statins, decrease vitamin B12 significantly.

These reports, combined with the current trends in obesity, type 2 diabetes and the inherent nutritional shortcomings in the Western diet, suggest that it is likely that nutritional deficits and even nutritional imbalances are more common than are recognized.

Maternal Vitamin B Status Before Pregnancy Affects Health of the Male Offspring

A study carried out in sheep found clear evidence linking maternal vitamin B9 and B12 status pre-conception to the health the male offspring later in life. This particular study compared the offspring from sheep fed a nutritionally normal diet to those fed a slightly deficient diet, but one that was still within accepted nutritional parameters, from eight weeks before conception, throughout the pregnancy and six days postpartum. While the pregnancy proceeded normally in both groups and both male and female offspring appeared normal and healthy at birth, continued monitoring across the lifespan of the sheep, showed remarkable changes in the health of the adult males conceived on the nutritionally deficient diets. These males were heavier, had significantly disrupted immune function, impaired glucose metabolism and increased blood pressure, than the females and in comparison to the offspring whose moms had more nutritionally sound diets. This slight change, towards the lower end of what is considered a nutritionally normal diet, had significant influence on long term health in the male offspring. This study also identified clear epigenetic markers in the offspring conceived with dietary deficiency.

Maternal Vitamin B Status, Breast Milk and Infant Health

Maternal vitamin demands do not end postpartum. Lactation increases the demand for maternal nutrients. Deficits in maternal vitamin status impacts infant health and development as well as maternal health and recovery. It should be clear that maternal vitamin deficiencies negatively affect maternal health. Even so, there has been some contention regarding the relationship between maternal vitamin status, fetal development, the quality of breast milk and subsequent infant health and development.

A review of studies assessing vitamin status in breast milk found widespread deficiency, with levels below what is considered adequate intake for proper infant development in most of the samples. The B vitamins (thiamine, riboflavin, B6, B12 and choline) were particularly inadequate.

What was particularly interesting about this study is that researchers found that nutrient deficiencies affect maternal health more so than infant health. Nutrients can be categorized into two groups, those that respond favorably to maternal supplementation with higher milk concentrations (Group 1) and those that do not (Group 2). Group 1 nutrients included thiamine, riboflavin, B6, B12, choline, retinol, vitamin A, vitamin D, selenium and iodine. These nutrietns are secreted into breast milk and depleted rapidly in breast milk when maternal nutrient status is low. Deficiencies in these nutrients can be supplemented and passed on through the breast milk. In this way, maternal nutrient status directly affects the quality of the milk. Group 2 nutrients (folate, calcium, iron, copper and zinc), on the other hand, do not respond as well to supplementation. Breast milk concentrations of these nutrients remain relatively unchanged by maternal status, even when maternal status is declining. Supplementation with Group 2 nutrients affects maternal health more so than infant health.

Take Away

Fetal and infant health and development can be severely impaired by maternal nutrient deficiencies during pregnancy and during breastfeeding. The period across which maternal nutrient status affects the health of her offspring should be extended to well before conception. The B vitamins are especially important to proper development and long term health and appear to regulate genetic expression via epigenetic mechanisms. Recognizing and treating the potential nutritional deficiencies in modern, western diets, may go a long way towards reducing maternal illness while improving fetal, infant, child and adult health for generations. A growing body of evidence, and indeed, common sense suggest that while vitamin B9 or folate is critically important to maternal and fetal health, deficiencies in the remaining B vitamins and other nutrients may be equally important.

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Are You Vitamin B12 Deficient?

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Chandler Marrs

Most women have a basic understanding of the relationship between vitamin B9 – folate or folic acid and health. Any woman who has ever been pregnant knows that folate deficiencies can cause neural tube defects in the developing fetus. To prevent these complications, we are given prenatal vitamins that contain folic acid. Folic acid is also added to a myriad of food products. Unfortunately, folate or vitamin B9 is only part of the equation. Vitamin B12 (cobalamin) must also be sufficient and maternal vitamin B12 deficiencies also lead to neural tube defects in the developing fetus. Beyond pregnancy, however, vitamin B12 deficiencies in children and adults elicit a host of debilitating and even deadly central nervous system symptoms, sometimes mistaken for multiple sclerosis or other ill-defined and unexplained conditions. As is the case with many apparently complicated conditions, Vitamin B12 is not often tested. Even when tested, the reference ranges are out of date and ill-defined, and so, deficiencies are not recognized easily.

Why Do I Need Vitamin B12?

Vitamin B12 is involved with a staggering number of physiological functions. One of its most important roles is in the formation of red blood cells. Individuals lacking an intrinsic factor to absorb dietary B12 (as in pernicious anemia), have a lower than normal number of red blood cells. Without enough vitamin B12, the red blood cells don’t divide normally and are too large. Vitamin B12 is also involved in the synthesis of the myelin sheaths around nerve fibers. There is a growing relationship between multiple sclerosis, which involves the disintegration of myelin and brain white matter and vitamin B12 deficiency. Finally, B12 is involved in approximately 100 functions including DNA, RNA, hormone, lipid and protein synthesis. Many women have dysregulated hormones connected to vitamin B12 deficiency. With so many core but disparate functions, it is easy to see why vitamin B12 deficiencies can be difficult to diagnose and devastating if left untreated.

How Common is B12 Deficiency?

The data suggest B12 deficiencies in the general population range from 3-6%. However, and this is a big however, individuals over the 60, women, vegetarians and vegans have as high as a 20-25% vitamin B12 deficiency rate. Vitamin B12 is found in the diet in red meat, dairy, fatty fishes and some vegetables. As more people refrain from red meats and dairy, deficiencies in B12 are on the rise. More importantly, because of increased medication use, the physiological demands of pregnancy and hormones, women are particularly susceptible to lower vitamin B12 concentrations. These deficiencies can be compounded as we age and the ability to absorb the vitamin decreases. The most common causes of vitamin B12 deficiency are, diet, pernicious anemia, medication, Hashimoto’s thyroid disease, and genetics (the MTHFR mutation).

Common Medications that Deplete Vitamin B12

Are you Vitamin B12 Deficient?

You might be. Many women are deficient in vitamin B12 and don’t even know it. The symptoms develop gradually over years and are often attributed to other conditions, such as MS, Parkinson’s, and a variety of psychiatric conditions. Research suggests that fully 74% of patients with vitamin B12 deficiency present with neurological symptoms. Here are some of the symptoms of vitamin B12 deficiency.

  • Tremors
  • Numbness and parathesias – tingling and other odd sensations in the extremities (~33%)
  • Gait (walking) and balance disturbances (~12%)
  • Loss of position sense
  • Psychiatric symptoms and cognitive difficulties (~3%)
  • Weight loss (~50%)
  • Low grade fever (~33%)
  • Muscle pain and weakness
  • Fatigue and apathy

Vitamin B12 Testing

Vitamin B12 status is typically assessed via a blood test. Normal ranges can be found here. As noted above, there is evidence to suggest that blood levels may not accurately reflect tissue levels and so many women may show normal blood levels of vitamin B12 but are deficient nonetheless. Other tests that may be of value include, elevated homocysteine levels and/or elevated methylmalonic acide levels. Elevated homocysteine levels are present in a number of conditions, including cardiovascular disease, thyroid disease and chronic migraine. Homocysteine may not be a sensitive indicator of vitamin B12 deficiency. However, it is a good marker of general ill-health. So far, the most accurate test for vitamin B12 is urinary methylmalonic acid testing.

If you think you might be deficient, here is a simple checklist to take before seeing your doctor. It is provided by the Pernicious Anemia Society: Checklist for Vitamin B12 Deficiency.

To learn more about Vitamin B12 Deficiency, watch this video.

 

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