by Dr. Dana Myatt

“Selective reporting” about the H1N1 virus and vaccine make it sound like getting a vaccination for the “pandemic flu” is a no-brainer. Thinking men and women should know the under-reported scientific conclusions and plain vanilla government statistics concerning this year’s “Panic-Demic” before making this seemingly simple but potentially life-threatening decision.

To that end I present these “inconvenient truths” (fully referenced) for your consideration. Please note that it is extremely politically incorrect to question the value of the flu vaccine.

In Health,
Dr. Myatt
 

Seven Inconvenient Truths About the 2009 H1N1 Flu Pandemic

by Dr. Dana Myatt

1.) What is a “Phase Six” Pandemic? (Probably NOT what You Think)

Contrary to popular thought (and most dictionaries), “pandemic” does not mean “large numbers” in WHO / CDC language. According to the World Health Organization’s (WHO) Pandemic Phase Descriptions, “pandemic” refers to distribution, not numbers or severity. Here is the WHO criteria for pandemics:

• A “Phase 4” pandemic means only that a virus is transmissible between humans.

• A “Phase 5” pandemic means only that one viral disease has been seen in two countries.

• A Phase 6 pandemic means only that one viral disease has been seen in three or more countries.

Again, the term “pandemic” does NOT refer to numbers of people affected or severity of the disease. (1)

For perspective, The WHO announced as of 20 September 2009 that there have been 3917 total deaths worldwide from H1N1, on par with world-wide mortality from any seasonal or other flu for this time of year. (2) Malaria kills an average of 3,000 people every dayin southeast Asia. (3)

2.) Is The H1N1 Flu Really a Danger to the U.S.?

Of less than 4,000 flu-related deaths world-wide, only 211 have occurred in the US as of August 2009. (4) This represents a death total lower than from seasonal flu for years 2005 through 2008 in the U.S. (5)

Adding H1N1 and seasonal flu together, flu-related deaths are still lower this year compared to previous “non-pandemic” years.

Not only is the total flu rate lower this year in the U.S., but the H1N1 flu has been much milder than predicted here and abroad. (6-10)

According to the WHO, most H1N1 infections are mild, occurring in numbers comparable to seasonal flues, with fast recovery and mostly without need for medical care. Mortality rates so far have been only a fraction of the number of those reported each year from seasonal flu. WHO also acknowledges that “Large outbreaks of disease have not yet been reported in many countries…” (11)

Harvard researcher Mark Lipsitch, PhD, explained at an Institute of Medicine meeting that on a 1 to 5 scale — with 5 being a 1918-like pandemic — this swine flu pandemic is a 1. Deputy Director of the CDC’s flu division, Daniel Jernigan, MD, concurs. “We are likely to have numbers that look very similar to what Dr. Lipsitch had,” Jernigan said. (12)

3.) Why H1N1-related deaths are actually smaller than reported in the U.S.

As of August 2009, ALL flu-associated deaths in the U.S. are being reported together. H1N1, seasonal flu and “influenza-like illness” (ILI) are added together to give the “flu mortality rate.” Reported illness and death totals, now include “influenza-like illness” (ILI) that in some cases may not be any form of flu at all. (13)

Other reports concede that a portion of reported H1N1 deaths have actually been caused by pneumonia, not the H1N1 virus itself. (14)

Because the new reporting system tallies deaths from all types of flu, the reported numbers of total flu deaths are not all attributable to H1N1. This means the true H1N1 mortality rate is only a portion of the total reported. Remember that deaths from all types of flu added together are lower in the U.S. this year than from the four previous “non pandemic” years before. (5,13)

3.) Flu vaccines provide little or no protection from the flu.

Vaccination is claimed to prevent the spread of influenza, protect individuals from acquiring the disease, and do so to a high degree of efficacy. Unfortunately, the majority of scientific studies do not support these claims. In fact, meta analyses (“master studies”) that look at large numbers of scientific studies and their outcomes, show the opposite. Influenza vaccine is minimally or not at all effective for most age groups. Here is how the numbers break down.

In children under two:

In children under the age of two, influenza vaccines are no more effective than placebo. (15)

One meta analysis evaluating fifty-one published studies with 294,159 observations found “no efficacy” in children under the age of two. (16) The authors conclude that “It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months old in the USA and Canada.”

Simply put, the authors question why the U.S. is targeting children under the age of two for vaccination when the studies show the vaccine to be ineffective in this age group.

In children over two:

The same meta analysis found influenza vaccines effective 33% of the time in children over the age of two. (16) Followed to it’s logical conclusion, this means the flu vaccines are ineffective 67% of the time in children over the age of two.

Another study found influenza vaccine ineffective up to age 5. (17)

In healthy adults:

A meta analysis evaluating 25 studies conducted on 59,566 adults age 14-40 found a mere 6% decrease of clinical influenza in those vaccinated. The conclusion: “Universal immunization of healthy adults is not supported by the results of this review.” (18)

The recent update to this study, pooling 38 published studies encompassing 66,248 healthy individuals aged 16 to 65 years, found that “serological flu” (lab numbers) were reduced but actual cases of flu were not reduced. This meta analysis concluded that improvements in overall flu rates in those vaccinated “was extremely modest.” (19)

In seniors:

Seniors over age 70 account for 75% of all flu-related deaths. Since 1980, the vaccination rate in seniors has increased from 15% to 65% but the death rate from flu has not declined. The authors conclude that “the evidence is insufficient to indicate the magnitude of a mortality benefit, if any, that elderly people derive from the vaccination program.” (20)

Contrary to popular belief, studies have found that secondary pneumonia in seniors is not decreased by flu vaccination, and that reduction of mortality through influenza vaccination has been greatly overestimated in this age group. (21,22)

5.) “Fast track” approval of flu vaccines, especially H1N1, leaves safety questions unanswered.

“Fast track” approval means that influenza vaccines do not have to go through the normal regulatory procedures. The H1N1 vaccine approval was especially fast because of the “pandemic” designation. One of the approved 4 vaccines was approved after testing in only 221 people for 21 days. (23) Another was approved after testing on 175 adults for 21 days. (24).

The World Health Organization (WHO) admits that people who get vaccinations will be the “field testers” of their safety. From the WHO website:

“Time constraints mean that clinical data at the time when pandemic vaccines are first administered will inevitably be limited. Further testing of safety and effectiveness will need to take place after administration of the vaccine has begun. (Author’s italics)

… On the positive side, mass vaccination campaigns can generate significant safety data within a few weeks. (Author’s italics) (25)

In other words, we won’t know the safety of these vaccines until we vaccinate millions of people (45 million is the U.S. “target” for October) (26,27); the side effects experienced by those vaccinated will be the “safety data.”

The U.S. Government conferred immunity from prosecution to drug manufacturers of the H1N1 vaccine in July 2009. (28)

6.) Vaccines May Be More Dangerous than the Flu Itself.

In 1976, 200 soldiers at Fort Dix were stricken with the flu, with one reported death. A pandemic was declared and nearly 40 million people in the U.S. received the 1976/H1N1 vaccine before the campaign was stopped due to an increase in Guillain-Barré syndrome, a paralytic autoimmune disease. (29)

More than 500 cases of Guillain-Barré syndrome were reported, 25 of which resulted in death. This “pandemic that wasn’t” never spread beyond Fort Dix. (30)

In a recent statement by the The American Academy of Neurology, experts said they don’t expect the 2009 H1N1 vaccine to increase risk of Guillain-Barré syndrome or other autoimmune disease but they acknowledged that this is a concern with any pandemic vaccine. (31)

Mild short-term reactions to the vaccine can include soreness, redness, or swelling at vaccination site, low grade fever, runny nose, headache, chills, tiredness/weakness and body aches and pains. (32) These symptoms are very much like the flu itself.

Life-threatening allergic reactions (anaphylaxis) and Guillain-Barré syndrome (a paralytic autoimmune disease) can also occur. (33)

These short-term side effects of influenza vaccination are easier to observe because of their close proximity to vaccination, beginning within minutes to several weeks. Long-term and/or cumulative effects of vaccinations are more difficult to monitor, and questions remain about the long-term safety of vaccines.

For example, the incidence of Alzheimer’s disease in adults and autism in children has skyrocketed in the last several decades. These rates are continued to increase. (34,35)

The cause of these increases is not known. Some camps maintain that these neurological disease escalations may be caused by vaccinations, especially since many vaccines still contain mercury, aluminum, formaldehyde and other neurotoxic compounds. (36-39)

The US government, CDC, FDA, and drug manufacturers claim there is no correlation between vaccines and these diseases, (40-43) although many question the quality of evidence used to draw this conclusion. (44,45)

7.) “Herd Immunity” Remains Speculative

“Herd immunity” (community immunity) is the belief that if a portion of society gets vaccinated, weaker members of “the herd” who do not respond satisfactorily to the vaccine (children under two and seniors over 65) will be protected from the flu because those around them have been vaccinated. Much evidence contradicts the concept of “herd immunity.” (46-49)

If healthcare workers get vaccinated, they purportedly decrease the risk of influenza in their high-risk patient, hence the “heavy push” that borders on mandate for health care workers to receive the vaccine. One large meta analysis found “no high quality evidence that vaccinating healthcare workers reduces the incidence of influenza or its complications in the elderly in institutions.” (50)

Conclusions

My purpose in presenting these statistics and studies is to assist the reader in drawing independent conclusions about the true risk of H1N1 flu and advisability of vaccination for same.

We are each responsible for our own “due diligence” when making decisions concerning our health, although many people defer to the media and government for their directives.

Here are the points I see from these studies and statistics:

1. The safety and effectiveness of H1N1 vaccines has not been proven.
2. The transmissibility of H1N1 flu is small and the severity mild compared to seasonal flu.
3. My risk of getting the H1N1 flu is small; my risk of dying from this flu is quite small and no greater than for any seasonal flu.
4. Flu vaccines confer little if any protection from influenza viruses in my age group.
5. There is much conflicting “proof” that by getting a vaccination, I help make others around me safer through “herd immunity.”
6. There are known short-term and possibly unknown long-term side effects from vaccines.

All things considered, I’m going to pass on the H1N1 flu vaccine. I believe there are far safer, better-proven methods to increase my resistance to H1N1 and make sure I have a mild case of it (as most cases are) if I do contract the flu.

References:

1.) WHO Pandemic Phase Descriptions and Main Actions by Phase. http://www.who.int/csr/disease/influenza/GIPA3AideMemoire.pdf
2.) WHO Website: Pandemic (H1N1) 2009 – update 67. 20 September 2009. http://www.who.int/csr/don/2009_09_25/en/index.html
3.) Center for Excellence in Disaster Management and Humanitarian Assistance. Researchers say new form of malaria poses threat to humans. Sep 11, 2009.
4.) Michael L. Tapper, MD, Chair. Seasonal and Pandemic Influenza: What You Need to Know About Prevention and Management.Medscape CME; Sept. 29 2009.
5.) Centers for Disease Control (CDC). 2008-2009 Influenza Season Week 37 ending September 19, 2009. http://www.cdc.gov/flu/weekly
6.) López-Cervantes M, Venado A, Moreno A, Pacheco-Domínguez RL, Ortega-Pierres G.On the spread of the novel influenza A (H1N1) virus in Mexico. J Infect Dev Ctries. 2009 Jun 1;3(5):327-30.
7.) Miller, Mark; Viboud, Cecile; Simonsen, Lone; Olson, Donald R.; Russell, Colin. Mortality and morbidity burden associated with A/H1N1pdm influenza virus: Who is likely to be infected, experience clinical symptoms, or die from the H1N1pdm 2009 pandemic virus? Version 2. PLoS Currents Influenza. 2009 Aug 26 [revised 2009 Sep 2]:RRN1013.
8.) Michaelis M, Doerr HW, Cinatl J Jr. An Influenza A H1N1 Virus Revival – Pandemic H1N1/09 Virus.Infection. 2009 Sep 18. [Epub ahead of print]
9.) Gallaher WR. Towards a sane and rational approach to management of Influenza H1N1 2009. Virol J. 2009 May 7;6:51.
10.) Senanayake SN. A pandemic that’s not bird flu? Pigs might fly. Med J Aust. 2009 Jul 6;191(1):38-40.
11.) World Health Organization website: http://www.who.int/csr/disease/swineflu/frequently_asked_questions/levels_pandemic_alert/en/index.html3
12.) Daniel J. DeNoon. First Doses of H1N1 Vaccine Coming Soon. Medscape Today, September 21, 2009.
13.) “2009 H1N1 Flu Situation Update – September 11, 2009”. CDC. 2009-09-11. http://www.cdc.gov/h1n1flu/updates/091109.htm. Retrieved 2009-09-30.
14.) Centers for Disease Control and Prevention (CDC). Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) – United States, May-August 2009. MMWR Morb Mortal Wkly Rep. 2009 Oct 2;58(38):1071-4.
15.) ##K## Smith S, Demicheli V, Di Pietrantonj C, Harnden AR, Jefferson T, Matheson NJ, Rivetti A. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004879.
16.) ##L## / Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004879.[## no efficacy in children under 2 33]
17.) ##M## Szilagyi PG, Fairbrother G, Griffin MR, Hornung RW, Donauer S, Morrow A, Altaye M, Zhu Y, Ambrose S, Edwards KM, Poehling KA, Lofthus G, Holloway M, Finelli L, Iwane M, Staat MA; New Vaccine Surveillance Network. Influenza vaccine effectiveness among children 6 to 59 months of age during 2 influenza seasons: a case-cohort study. Arch Pediatr Adolesc Med. 2008 Oct;162(10):943-51.
18.) ##N## Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2004;(3):CD001269.
19.) ##O## Jefferson TO, Rivetti D, Di Pietrantonj C, Rivetti A, Demicheli V. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD001269.
20.) ##P## Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66.
21.) ##Q## Eurich DT, Marrie TJ, Johnstone J, Majumdar SR. Mortality reduction with influenza vaccine in patients with pneumonia outside “flu” season: pleiotropic benefits or residual confounding? Am J Respir Crit Care Med. 2008 Sep 1;178(5):527-33. Epub 2008 Jun 12.
22.) ##R## ackson ML, Nelson JC, Weiss NS, Neuzil KM, Barlow W, Jackson LA. Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study. Lancet. 2008 Aug 2;372(9636):398-405.
23.) ##S## Greenberg M, Lai M , Hartel G., et al. Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine — Preliminary Report. New Eng J Med. September 10, 2009.
24.) ##T## Clark T, Pareek M, Hoschler K, Dillon H, et al. Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine — Preliminary Report.New Eng J Med. September 10, 2009.
25.) ##U## WHO Website: Safety of pandemic vaccines: Pandemic (H1N1) 2009 briefing note 6. http://www.who.int/csr/disease/swineflu/note s/h1n1_safety_vaccines_20090805/en/index.html
26.) ##V## Daniel J. DeNoon. H1N1 Flu Vaccine Fast-Tracked to September? WebMD Health News, July 17, 2009.
27.) ##W## Daniel J. DeNoon. First Doses of H1N1 Vaccine Coming Soon. Medscape Today, September 21, 2009.
28.) Federal Register. Vol. 74, No. 121. Thursday, June 25, 2009. http:edocket.access.gpo.gov/2009/pdf/E9-1494 8.pdf
29.) ##Y### Centers for Disease Control and Prevention (CDC). General Questions and Answers on Guillain-Barré syndrome (GBS).September 14, 2009. http://www.cdc.gov/h1n1flu/vaccination/gbs_qa.htm
30.) ##Z## United Stated Dept. of Health and Human Services. http://www.hhs.gov/nvpo/pandemics/flu3.htm
31.) Gandey A. Report New Cases of Guillain-Barré After H1N1 Flu Vaccine. Medscape Medical News, September 1, 2009.
32.) ##AB## Influenza Division, National Center for Immunization and Respiratory Diseases. Prevention and Control of Seasonal Influenza with Vaccines Recommendations of the Advisory Committee on Immunization Practices (ACIP), July 24, 2009 / 58(Early Release);1-52.
33.) ##AC## Centers for Disease Control and Prevention (CDC).Seasonal Flu Shot Questions & Answers. Accessed Oct. 7, 2009. http://www.cdc.gov/flu/about/qa/flushot.htm
34.) Hebert, LE; Scherr, PA; Bienias, JL; et al. “State-specific projections through 2025 of Alzheimer’s disease prevalence.” Neurology 2004; 62:1645.
35.) U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Vital and Health Statistics: Mortality Trends for Alzheimer’s Disease, 1979–91. Series 20: Data From the National Vital Statistics System No. 28. Jan 1996. http://www.cdc.gov/nchs/data/series/sr_20/sr 20_028.pdf
36.) AF / AFLURIA Manufactured by CSL Limited: Package insert: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM182401.pdf
37.) AG / Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM182406.pdf
38.) Novartis Vaccine (Fluvarin): http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM182242.pdf
39.) sanofi pasteur 10 September 2009_v0.3 449/454 Influenza A (H1N1) 2009 Monovalent Vaccine: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM182404.pdf
40.) Centers for Disease Control and Prevention: Immunization Safety and Autism Thimerosal and Autism Research Agenda. Last updated – January 30, 2009. Accessed online 10-07-09: http://www.cdc.gov/ncbddd/autism/documents/vaccine_studies.pdf
41.) Centers for Disease Control and Prevention (CDC). Vaccine Safety: Measles, Mumps, and Rubella (MMR) Vaccine. December 23, 2008. Accessed online 10-07-09 http://www.cdc.gov/vaccinesafety/updates/mmr_vaccine.htm
42.) Food and Drug Administration. Thimerosal in Vaccines. Website accessed 10-07-09. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm096228.htm#saf
43.) Karen Midthun, M.D. Concerns Regarding a Potential Link Between Vaccines and Autism. FDA News and Events, April 26, 2001. FDA Testimony before the House Committee on Government Reform. Accessed 10-07-09 http://www.fda.gov/NewsEvents/Testimony/ucm115226.htm
44.) ROBERT F. KENNEDY JR. Deadly Immunity. Rolling Stone. Posted Jun 20, 2005.
45.) Cal-Oregon Vaccinated vs. Unvaccinated Survey. Generation Rescue, PORTLAND, OR, Sep 25. Accessed 10-07-09 http://www.generationrescue.org/survey.html
46.) Glanz JM, McClure DL, Magid DJ, Daley MF, France EK, Salmon DA, Hambidge SJ. Parental refusal of pertussis vaccination is associated with an increased risk of pertussis infection in children. Pediatrics. 2009 Jun;123(6):1446-51.
47.) Cheek JE, Baron R, Atlas H, Wilson DL, Crider RD Jr. Mumps outbreak in a highly vaccinated school population. Evidence for large-scale vaccination failure. Arch Pediatr Adolesc Med. 1995 Jul;149(7):774-8.
48.) Briss PA, Fehrs LJ, Parker RA, Wright PF, Sannella EC, Hutcheson RH, Schaffner W. Sustained transmission of mumps in a highly vaccinated population: assessment of primary vaccine failure and waning vaccine-induced immunity. J Infect Dis. 1994 Jan;169(1):77-82.
49.) Sutter R.W, Patriarca P, Cochi SL, Pallansch MA, et al. Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children. The Lancet, Volume 338, Issue 8769, Pages 715 – 720, 21 September 1991.
50.) Thomas R, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database of Systematic Reviews, Issue 3, 2009.

Figure 1: The NO‾/ONOO‾Cycle

Key to Figure 1: The NO‾/ONOO‾ Cycle “Players”

• Nitric oxide (NO‾) is a naturally occurring “messenger molecule” in the body and also a pro-oxidant and free radical. Depending on the amount and where it is released, NO can be either beneficial or toxic. (141-145,223)
  Nitric oxide is known to play a role in blood pressure regulation, blood clotting, immunity, digestion, the special senses (sight and smell), and possibly learning and memory. Abnormal levels of NO‾ may play a role in diseases such as atherosclerosis, diabetes, stroke, hypertension, impotence, septic shock, and long-term depression. (52,145) In ME/CSF/FM and related multi-system diseases, research suggests that excess NO‾ may be a primary contributor to long-term energy depletion and immune dysfunction. (101,141-142,223)
• Superoxide (O2‾) is a potent free radical. Like nitric oxide (NO‾), O2‾ has independent deleterious effects when expressed in excess. Superoxide reacts with NO‾ to form ONOO‾.
• OONO‾ (peroxynitrite) is a potent oxidant that damages cells. It is formed when NO‾ and O2‾ react with each other. Peroxynitrite in turn acts through multiple mechanisms to regenerate its precursors, NO‾ and O2‾. In this way, a “vicious cycle” of damage creating more damage begins.

Consequences of Superoxide (O2‾) Excess:

1.) Inflammation (130,137)
2.) Vaso-spasm (131)
3.) Endothelial dysfunction (132,134,135,138,139)
4.) Associated with retinal cell death, pulmonary hypertension, general hypertension, atherosclerosis, neurodegenerative disease, type II diabetes (73,132,134,136-140)
5.) Decreased cellular respiration (133)
6.) Cell death (133) + Consequences of Nitric Oxide (NO‾) Excess:

1.) Cellular energy depletion (97, 120)
2.) DNA damage (98-100, 118,123)
3.) Neurotoxicity, neuronal cell death and brain injury (52, 57, 58, 84,100-104,111-113, 115,123)
4.) Hypersomnolence and sleep apnea (102, 105)
5.) Lung injury (61,62,128,129)
6.) Increased pain perception and lowered pain threshold (53, 59)
7.) Lowered blood pressure (224-225)
8.) Inhibition of the methylation cycle (106, 107)
9.) Formation of carcinogenic substances (99)
10.) Increased inflammation (61, 62, 110,120,121,125,126, 130)
11.) Cytotoxicity (68,114,115,120, 123)
12.) Modification of cellular proteins (100,123)
13.) No is associated with Alzheimer’s, Arthritis, Parkinson’s, stroke, hemorrhagic shock, cancer, viral infections (57, 58, 97,98,113,115, 120,121,122,123)
14.) Damaged mitochondria (108,109,111,112, 114,115,127)
15.) Suppressed immune system (122)
16.) Assisted viral replication and pathogenesis (122, 124, 126,127)
→ Consequences of Excess Peroxynitrite (ONOO‾)

1.) Neurotoxic (72,74,76,85, 88,89)
2.) Cytotoxic (68,82-84,87,119)
3.) Increases lipid peroxidation (54,87,90,119,125)
4.) Retinal cell death (73,75,86)
5.) DNA damage (77,87,118,119,125)
6.) Decreased mitochondrial respiration (cellular oxygen)
(69,77,78,90,92,119)
7.) Increase viral replication (80)
8.) ONOO- is associated with Alzheimer’s disease, rheumatoid arthritis, atherosclerosis, lung injury, amyotrophic lateral sclerosis, HIV, multiple sclerosis, kidney damage, Parkinson’s disease, Huntington’s disease, Sjögren’s syndrome, septic shock and other diseases. (57,72,74,78,80,81,84,87,88,89,91)

Fig. 2: Independent Consequences of Increased Superoxide (O2‾ ), nitric oxide (NO‾ ) and peroxynitrite (ONOO‾ ).

Dr. Bell, one of the first physicians to recognize ME/CFS as a discrete medical condition, proposes in his book Cellular Hypoxia and Neuro-Immune Fatigue that cellular hypoxia may be the underlying factor in ME/CFS and related multi-system diseases. (146). This is consistent with the NO‾/ONOO‾ theory, because injuries of many types result in decreased oxygen (hypoxia) to the cell, thus initiating this destructive runaway cycle.

Hydroxocobalamin Breaks the NO‾ / ONOO‾ Cycle

Hydroxocobalamin (cobinamide), a unique form of vitamin B-12, is a potent nitric oxide (NO‾) scavenger. It is the only form of vitamin B12 that effectively neutralizes the NO‾ molecule. Hydroxocobalamin is the preferred form of vitamin B-12 required to break the NO‾/ONOO‾ vicious cycle of cellular damage. (147-149)

The Methylation Cycle and ME/CFS

The Methylation Cycle is a biochemical pathway required for the manufacture of DNA, RNA, phospholipids (myelin sheath of nerves), neurotransmitters, adrenal hormones and more than 100 enzymes. A fully functional methylation cycle is also required for numerous detoxification reactions. (150-157)

A defect in the methylation pathway is a second proposed mechanism in the development of ME/CFS. The research of Dr Rich van Konynenburg has been instrumental in demonstrating the intricate interrelationship between the methylation cycle and ME/CFS. (158)

Methylation defects cause reduced detoxification ability, decreased production of serotonin, dopamine, melatonin and other neurotransmitters, decreased production of adrenal hormones, increased levels of toxic homocysteine, and decreased cellular energy production. (159-163)

This reduced production of vital neurotransmitters may explain the feelings of depression and despondency that frequently strike ME/CFS victims and would explain the positive effects often achieved with the use of SSRI and other mood-altering pharmaceuticals. Unfortunately, many clinicians interpret the improvement seen with antidepressant medications as “proof” that ME/CFS is a psychiatric illness when in fact an understanding of the methylation pathway defect offers solid evidence of a biochemical basis for depression and low energy in ME/CFS.

Figure 3: The Methylation Cycle

Note the overlap between the NO‾/ONOO‾ Cycle and the Methylation Cycle where excess NO‾ blocks methionine synthase, a critical enzyme in the methylation cycle. (106, 164-167)

The methylcobalamin form of vitamin B-12 is a required nutrient in the Methylation Cycle. If any one step in the methylation cycle fails, the entire cycle fails.

Vitamin B12: Which Form is Best?

What we know as Vitamin B-12 is actually a collection of four related but different cobalt-containing molecules. Each of these forms plays a distinct role in the body as follows:

Hydroxycobalamin is a unique form of B12 that quenches excess nitric oxide (NO‾), the precursor to peroxinitrite (ONOO‾).(147-149,172-176) Hydroxocobalamine (and methylcobalamine) are also more effective at treating neurological disorders than cyanocobalamine. (168)

Hydroxocobalamin participates in detoxification, especially cyanide detoxification. Cyanide levels are typically elevated in smokers, people who eat cyanide-containing food (like cassava) and those with certain metabolic defects. Excess cyanide in the tissues blocks conversion of cyanocobalamin to methylcobalamin or adenosylcobalamin. In such instances, hydroxocobalamin is the vitamin B-12 of choice. (169-171) Hydroxycobalamin is FDA- approved as a treatment for cyanide poisoning. (214

Methylcobalamin is considered by many researchers to be the most active form of vitamin B12. (177-179) It is the requisite form of vitamin B-12 in the Methylation Cycle. (179-186). Methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.(187-188) and promotes nerve cell regeneration. (189) Methylcobalamine is the only form of vitamin B-12 that participates in regulating circadian rhythms (sleep/wake cycles). It has been shown to improve sleep quality and refreshment from sleep, as well as increased feeling of well-being, concentration and alertness. (190).

Adenosylcobalamin (dibencozide), another highly active form of vitamin B12, is essential for energy metabolism (191) and is required for normal myelin sheath formation and nucleoprotein synthesis. Deficiencies are associated with nerve and spinal cord degeneration. (192-193)

Cyanocobalamin, the most common form of B12 found in nutritional supplements, is a synthetic form of B12 not found in nature. It has the lowest biological activity and must be converted in the liver to more biologically active forms. This conversion is inefficient and some people who may not benefit from cyanocobalamine due to lack of assimilation or conversion. (194-195) However, the cyano form of B12 is needed to balance hydroxycobalamin in performing its NO-quenching function and should therefore be included in hydroxocobalamine supplements. (176)

Who is Vitamin B12 Deficient and Why?

Research shows that a much larger segment of the general population is vitamin B12 deficient than previously thought. Recent studies indicate that up to 78% of seniors are deficient. (196-197)

Irritable bowel syndrome (IBS), seen in as many as 77% of CFS patients and 78% of FM patients (198-199) is a major cause of vitamin B12 deficiency. (200) This leads one to ponder the “which came first, the chicken or egg” nature of this: are ME/CFS patients B12 deficient because of IBS, or is IBS a result of cellular or neurological insult caused by B12 deficiency?

Other high-risk groups for B12 deficiency include those who use acid-blocking or neutralizing drugs (such as Prilosec, Prevacid, Nexium and others) (201-204), drugs which impair intestinal absorption (such as Metformin, Questron and Chloromycetin) (205), and people who have had gastric surgery. (206-207) Bacterial overgrowth of the small intestine, which occurs frequently in people with ME/CFS and low stomach acid, is a predisposing factor for B12 deficiency because the bacteria themselves use vitamin B12. (208-209)

The most recent and disturbing studies suggest that vitamin B12 deficiency is more prevalent in young adults than previously thought. (210-211). One study found that vitamin B12 deficiency was similar in three age groups (26-49 years, 50-64 years, and 65 years and older), but that early symptoms were simply less apparent in the young. This study also found that those who did not take a vitamin B12-containing supplement were twice as likely to be deficient as supplement users, regardless of age. (210)

Secondly, unlike other water-soluble vitamins, B12 is stored in the liver, kidneys and other tissues. Deficiencies of B12 often appear so slowly and subtly as to go unnoticed, and blood tests for vitamin B12 levels miss early deficiency states at least 50% of the time. (212-213)

Why Vitamin B12 MUST Be Obtained From Supplements

Medical science once believed that few people were vitamin B12 deficient. This false assumption may stem from the fact that vitamin B12 is produced in the body by a normal, healthy population of bowel bacteria.

Foods are not a significant source of vitamin B12. Meat, milk, eggs, fish, and shellfish contain the highest amount of B12 but only 50% of this is absorbable even in a healthy gut. (215) Vegetarian sources of vitamin B12, such as algae, are not bio-available and do not make significant contribution to dietary vitamin B12 levels. (216)

Further, absorption is hampered by low stomach acid, IBS, and bacterial overgrowth of the small intestine — conditions which are common in ME/CFS sufferers. The US Institute of Medicine recommends that adults over 50 obtain their vitamin B12 from supplements. (14)

Oral vs. Injectable: Which is Best?

Although vitamin B12 has previously been given by injection, it is now accepted in conventional medicine that oral vitamin B12 is equally as effective as injection in treating pernicious anemia and other B12 deficient states. (214, 217-220).

According to The National Institutes of Health (NIH), oral vitamin B12 supplementation is extremely safe (221-222). It is also as effective as injections, (14,219-220) and inexpensive and more convenient compared to injection. (220)

All Roads Lead To B12: Conclusions and Recommendations

The suffering from ME/CFS and other multi-system diseases is widespread and devastating. This affliction is beginning to receive more attention, perhaps because of the activism of those affected and the dedication of ME/CFS researchers and clinicians. Current research is providing us with new insights into the underlying mechanisms of this complicated illness.

The Nitric Oxide / Peroxynitrite model (NO‾/ONOO‾) and The Methylation Cycle have emerged as two likely contributory mechanisms to ME/CFS and other multi-system diseases including Fibromyalgia (FM), Lyme Disease, Multiple Chemical Sensitivities (MCS), PTSD and Gulf War Syndrome. Deficiencies of either of two forms of vitamin B12 — hydroxocobalamin and/or methylcobalamin — play a significant role in these biochemical processes.

Since Vitamin B12 (especially the hydroxocobalamin and methycobalamin forms) offer such potential benefits for ME/CFS and other multi-system disease sufferers — without known risks — it seems reasonable to suggest that anyone suffering with ME/CFS or other multi-system illness should consider taking a supplement containing these two important forms of vitamin B12.

Furthermore, because of the balancing effect that cyanocobalamin has on hydroxycobalamin (176) and the protective and regenerative effect that adenosylcobalamin exerts on the myelin sheath of nerves (192-193), these forms should also be considered as an important part of any complete vitamin B12 supplement.

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