“Ketogenic” means that the diet causes the liver to manufacture ketones. Ketones are small water-soluble compounds that are metabolized like fats. Unlike fats, they do not need carnitine transport to reach mitochondria. They can be used for energy by every mitochondria-containing human cell type. This makes them one of the most disease-resistant sources of dietary energy. There are few things that can go wrong with ketone metabolism.

Ketogenic diets have several major benefits for neurological conditions:

• They relieve neuronal starvation from cognitive hypoglycemia of any cause.
• They stimulate the innate immune response against intracellular pathogens, helping to heal brain infections.

Recent work has identified a third benefit from ketogenic diets: They eliminate an excess of glutamate. In a carbon isotope study, feeding the ketone beta-hydroxybutyrate in place of glucose caused less glutamate to be formed in the brain:

The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. [1]

This is important because excessive brain glutamate is “excitotoxic” and kills neurons. Glutamate excitotoxicity causes damage in a host of conditions including

spinal cord injury, stroke, traumatic brain injury and neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, alcoholism or alcohol withdrawal and Huntington’s disease. [2]

Other diseases in which damage from glutamate excitotoxicity is important include epilepsy, schizophrenia and various mood and anxiety disorders.

Migraines and Glutamate

My sister’s husband gets frequent migraines, so I keep an eye out for papers about migraines. A new paper in Nature Genetics finds that people with common migraine tend to have a mutation in a regulatory sequence for genes that control glutamate abundance. [3]

People with the mutation are prone to glutamate excitotoxicity:

[A] DNA variation found between the PGCP and MTDH/AEG-1 genes on chromosome 8 appears to be associated with increased susceptibility to common migraine. The variant appears to alter the activity of MTDH/AEG-1 in cells, which regulates the activity of the EAAT2 gene: the EAAT2 protein is responsible for clearing glutamate from brain synapses in the brain….

“Although we knew that the EAAT2 gene has a crucial role to play in neurological processes in human and potentially in the development of migraine, until now, no genetic link has been identified to suggest that glutamate accumulation in the brain could play a role in common migraine,” says co-senior author of the study Professor Christian Kubisch of University of Ulm, Germany (previously at the University of Cologne where he conducted his research for this study.) “This research opens the door for new studies to look in depth at the biology of the disease and how this alteration in particular may exert its effect.” [4]

If glutamate excitotoxicity causes migraines, then it’s likely that migraine sufferers would benefit from a ketogenic diet.

How Do You Eat a Ketogenic Diet?

The safest and healthiest way to eat a ketogenic diet is by:

• Restricting carbohydrate consumption to 200 calories per day from “safe starches” like rice, taro, and sweet potatoes.  70 grams of cooked white rice, 150 grams of taro, and 300 grams of sweet potato are an appropriate daily ration.
• Eating massive amounts of coconut oil. The short-chain fats in coconut oil are the most “ketogenic” of foods, i.e. the most readily turned into ketone bodies. 6 to 8 fluid ounces (12 to 14 tablespoons) per day of coconut oil is an appropriate daily ration.

Supplements with vitamin C and selenium should also be increased on a ketogenic diet.

Conclusion

Research on ketogenic diets as a therapy has focused on epilepsy for decades, with some recent interest in using these diets as a therapy for brain cancer. But really, they are likely to be helpful against nearly all brain and neurological conditions, and probably all solid tumor cancers and many infectious diseases as well.

Rather than waiting for the glacial progress of modern biomedical research, which needs decades to assemble sufficient evidence to get an application for funding for a clinical trial past skeptical reviewers, anyone with a brain or neurological condition should simply experiment with a ketogenic diet themselves to see if it helps. Odds are it will.

References

[1] Lund TM et al. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. J Neurochem. 2009 Jul;110(1):80-91. http://pmid.us/19457063.

[2] Wikipedia, “Excitotoxicity,” http://en.wikipedia.org/wiki/Excitotoxicity.

[3] International Headache Genetics Consortium et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010 Aug 29. [Epub ahead of print] http://pmid.us/20802479.

[4] “First Genetic Link to Common Migraine Exposed,” Physorg.com, Aug. 29, 2010, http://www.physorg.com/news202139760.html.

Stumbled upon your site while searching for information abouit vitamin d dysreguiation and was so impressed that I had to tell you so. You gave me a much more comprehensive insight into some of vitamin D’s ecosystem that I had never imagined might be the case.

All of which prompts me to mention my vitamin D enigma that has my doctor stumped. When I retired 15 years ago as a consulting psychologist I moved from the San Francisco Bay area to the Seattle area to be close to my son. Then I got so caught up in using the computer to follow a range of interests that I seldom got out of doors — and the latitude here limits the D I could get from sunlight anyway — and I get virtually no vitamin D from my diet since I am allergic to seafood. The upshot was that as I moved into my 80’s I was confronted with a variety of physical changes that that I now think were due to severe vitamin D deficiency. Three or four teeth just crumbled over a period of a month or so, I developed adult scoliosis, and my blood pressure (always a bit high) went out of control, hitting the 190’s and low 200’s. I refused blood pressure pills since I had previously been damaged by them, and instead began taking increasing amounts of vitamin D. When I hit 15,000 a day it began to drop, and settled at the 150 to 175 range. Three months ago my vitamin D level was measured as part of a yearly physical exam, and when my doctor found that my NgL level was 92 he said that he had never seen one that high and asked me to cut my intake to 10,000 units for starters. I had tried to do that three times previously, and my blood pressure went back up the first two times and the third time my face began to swell. This fourth time didn’t work either, with my blood pressure going up after a few days of starting. I stuck it out for two weeks and then went back to the 15,000 IUs. But, as opposed to my three earlier tries, when blood pressure was back to my normal in a week, this time it took a six weeks before the blood pressure came down again. So the enigma that I have has to do with this weird relationship between my vitamin D “requirement” and my blood pressure.

Otherwise I feel better than fine. My Google research led me to a curcumin program a while back and that has brought back my original dark brown hair color, and recently I found that I now longer had to get up to go to the bathroom every night(as has been the case for years). And as of a week ago I found that my prostate is shrinking. More importantly, the AMD I have in both eyes is gradually reversing to the point where I no longer am a member of the enlarged print gang. So as far as I know everything is working fine and I don’t have a chronic anything!

These conditions rarely regress on conventional medical treatments, so to achieve this degree of success is a medical miracle.

Like Charles’s doctor, I was stumped by this at first, but then I thought to look up some other case reports of patients who benefited from super-normal 25OHD. Autism reports from Dr. John Cannell of the Vitamin D Council gave me an idea that might solve Charles’s enigma.

Background on Vitamin D

For most people, health is optimized by obtaining about 4,000 IU/day of vitamin D3 from sun or supplements, leading to a serum 25-hydroxyvitamin D (25OHD) level of 35 to 50 ng/ml in people of Eurasian ancestry or 30 to 40 ng/ml in people of African ancestry.

Not long ago I did a post on the characteristic pattern of vitamin D dysregulation in chronic infections. In chronic infectious diseases, low 25OHD is often found with elevated levels of the more active metabolite 1,25-dihydroxyvitamin D (1,25D). Possible mechanisms for this include:

• Infections making cell membranes leaky to 1,25D, causing it to spill out of cells into the blood, thus reducing activation of the nuclear membrane’s vitamin D receptor (VDR).
• Infections obstructing or downregulating the VDR, causing the body to attempt to upregulate VDR activation by increasing conversion of 25OHD to 1,25D. Both forms of vitamin D are active ligands for the VDR, but 1,25D is far more active, so converting 25OHD to 1,25D means more activation of the VDR.

Inventing ways to block the VDR or move 1,25D out of the cell would be fitness-enhancing mutations for bacteria or viruses, since activation of the VDR triggers production of antimicrobial peptides that are central to intracellular immunity. Since bacteria evolve a lot faster than humans, it should be no surprise that pathogens have been able to evolve these capabilities.

But Some Diseases Have The Opposite Pattern

But some people have diseases that produce the opposite pattern. In their diseases, “normal” 25OHD levels are associated with impaired health, while unnaturally high 25OHD levels normalize health.

Charles is a great example:

• He is taking super-normal amounts of vitamin D: Sunshine alone will generally not produce sustained creation of more than 4,000 IU/day. (Yes, I know that 10,000 IU can be produced in half an hour in D-deprived individuals, but if that person went out in the sun every day vitamin D production would soon decrease.) So 15,000 IU/day is roughly four times the normal dose.
• He is achieving super-normal levels of 25OHD that would probably be toxic for most adults. The maximum 25OHD levels achievable through sunshine vary among persons, but are generally between 48 and 80 ng/ml. [1] Moreover, human cells turn on the gene CYP24A1, which codes for the main vitamin D-degrading enzyme, at 25(OH)D levels below 100 ng/ml. [2] It seems that evolution has designed us to keep 25OHD levels around 50 ng/ml or lower – certainly below 80 ng/ml. So Charles’s 92 ng/ml is well above the levels achievable by natural methods.

Since both 25(OH)D production and degradation have been strongly selected for by evolution, we can be confident that in healthy people of reproductive age it’s not a good idea to supplement at 15,000 IU/day or drive serum 25(OH)D to 92 ng/ml.

And what limited clinical evidence we have supports that conclusion. Those tropical lifeguards who get their serum 25(OH)D levels up to 80 ng/ml? They have three times the rate of heart attacks of those with normal 25(OH)D. [3]

Aside:  Their high rate of heart disease may be due to vitamin K2 deficiency. Charles, please be sure to supplement vitamin K2, preferably a mix of MK-4 and MK-7 forms, along with your D.

Yet whereas healthy younger people would experience toxicity at Charles’s vitamin D dose or 25OHD level, Charles’s health improves.

Autism and Vitamin D

Let’s consider a few other cases where super-physiological 25OHD levels have cured diseases. Dr. John Cannell of the Vitamin D Council is the most prolific writer on the subject of vitamin D, and in his newsletter has collected a number of reports of diseases being cured by pharmacologic doses of vitamin D.

Here’s a sample case report of the recovery of an autistic child, from the January 2010 newsletter. My comments are italicized within brackets:

At age 2.5 years, between December 2007 and January 2008, my son experienced a fairly dramatic onset of symptoms that led to his diagnosis of autism….

Neither the DAN Doctor nor our pediatrician would write a prescription for a therapy light, so we purchased one on our own and found it made no discernible impact on his symptoms. [PJ: No matter how much sunlight or UV light the child is exposed to, it is not possible to raise 25OHD levels enough to impact the disease.]…

I … decided we would try a vitamin D supplement. Our pediatrician did not encourage any dose higher than 400 i.u. (that found in a typical multivitamin) but did write a script to have his 25-hydroxy level tested. In August his level was 37, so we started him on 5,000 iu daily [PJ: Since vitamin D needs scale by body weight and this is a young child, this is a very high dose – comparable to Charles’s 15,000 IU] and had his level retested on October 21st. By October his level was 96 ng/ml [PJ: A super-normal level, close to Charles’s 92 ng/ml] The pediatrician was concerned that this was too high and told us he should not have more than 400 iu per day.

Knowing that Nov–March are typically his worst months, we reduced the dosage down only to 3,000 iu from October through mid-December. At an appointment in December our son was doing wonderfully (none of his usual fall/winter symptoms yet evident) and the pediatrician told us 3,000 iu was too much and that we should be giving no more than 400 iu. In mid-December we reduced the dose to 1,500 iu. [PJ: This would still be a high dose for a normal 4 year old]  By the beginning of January we noted a marked loss of eye contact. [PJ:  But this “high” dose is insufficient] We also noted that our son was again interchanging his right hand for writing and eating (after using his left hand exclusively for 8+ months). We increased his vitamin D level to 4,000 iu daily in early January. On January 11 we had his 25-Hydroxy level checked on January 11 and found that it was 89. [PJ: Again, the disease is present at a “normal” 25OHD of 37 ng/ml but absent at a super-normal level around 90 ng/ml.] By the end of January, we and his grandparents noted improvement in his eye contact.

In January 2010 we attended his preschool conferences. The teacher had marked cards with the following code (1=age appropriate, 2=developing, 3=area of concern). Our son received 1s in all areas with the exception of hopping on one foot and balance beam where he received 2s. We were told that he is on par with or ahead of his peers in all areas (academic, fine motor, etc.), and that his teacher had noted no unusual symptoms or concerns.

So the child’s autism is essentially cured on super-normal doses of vitamin D that raise serum 25OHD to around 90 ng/ml.

Is it just a coincidence that Charles and the autistic child experienced a normalization of health at the same 25OHD level? And that in both cases, the normalization occurs after a few weeks of high-dose vitamin D supplementation?

Hypothesis:  Impaired Production of 1,25D from 25OHD

Let’s step back for a moment and think about what would cause health to normalize with super-normal 25OHD.

Suppose that for some reason, cells were unable to convert 25OHD to 1,25D. What would happen?

First, cells would have unusually low levels of 1,25D for any given level of 25OHD. Since 1,25D is more than a hundred-fold more active as a VDR ligand than 25OHD, this means that their level of VDR activation would be reduced. 

By how much?  In many cells, there seems to be a nearly equal balance between 25OHD and 1,25D activation of the VDR. As one paper notes:

the high serum concentration of 25(OH)D3 [500–1000 times higher than 1,25(OH)2D3] overcomes its low affinity for the receptor [500 times lower than 1,25(OH)2D3]. [4]

If the higher activity of 1,25D is almost precisely balanced by its lower abundance, then a cell’s loss of ability to make 1,25D will cut VDR activation in half.

So to restore VDR activation to normal levels, you would need to raise 25OHD to double normal levels: 70 to 100 ng/ml.

This would fit the cases of the autistic child and of Charles, both of whom reached normal health at around 90 ng/ml.

Genetic Defects: Pseudo-Vitamin D Deficiency Rickets

Mutations in the gene CYP27B1, which codes for the enzyme that turns 25(OH)D into 1,25D, create a disease called pseudo-vitamin D deficiency rickets (PDDR) or vitamin D-dependent rickets type I (VDDR I). [5]

PDDR is characterized by muscle weakness and rickets.

One nice thing about diseases caused by a single genetic defect is that they are easily reproduced in animals. PDDR can be reproduced in mice by knocking out the CYP27B1 gene.

CYP27B1 knockout mice are growth retarded, hypocalcemic, and have poor bone mineralization. The negative effects are all apparent at normal 25OHD levels of 36 ng/ml. But when the mice were given high doses of vitamin D, raising 25OHD levels to 144 ng/ml, their health was normalized. [4]

Other insights into inadequate 1,25D production have been obtained through mice deficient in vitamin D receptors. Their characteristics:

VDR mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. [6]

“Alopecia” is hair loss. “Kyphosis” is the familiar hunchback that many elderly develop. Osteoporosis is a familiar symptom of aging, as is loss of muscle, wrinkled skin, hardening of the arteries and stiffening of joints (“ectopic calcification”), loss of hearing and balance, and – approaching death.

These are all symptoms of a syndrome that is commonly called “aging.”

Here is what VDR knockout mice look like [7] (click to enlarge):

Note what happens when you can’t activate the VDR: hair loss, wrinkled skin. You get old before your time. VDR knockout mice die at an age of 10.6 months, compared to 20.5 months in wild-type mice. [7]

Our Cases Resemble PDDR

In his essay “Vitamin D Theory of Autism,” (http://www.vitamindcouncil.org/health/autism/vit-D-connection.shtml) Dr. Cannell notes similarities between PDDR and autism:

While no one has assessed afflicted [with PDDR] children for signs of autism, these children clearly display autistic markers such as hypotonia (flabby muscles), decreased activity, developmental motor delay, listlessness, and failure to thrive.

It is quite possible that autism results, as Dr. Cannell argues, from insufficient activation of the VDR during developmental ages. [8]

Similarly, what about the conditions Charles suffered from?  Tooth loss, bone mineral deficiencies, and scoliosis are all classic manifestations of rickets, and vitamin D deficiency is a known risk factor for high blood pressure and for arterial hardening. Finally, his recovery of hair color might be a result of restored vitamin D function:  the VDR promotes hair cycling. [9]

What Mechanisms Might Produce a CYP27B1 Deficiency in the Elderly?

It’s a safe bet that Charles does not have a genetic defect in CYP27B1. If he has a CYP27B1 dysfunction, it must have been acquired in old age.

What could have created the problem?  I don’t know, but speculation is permitted at PerfectHealthDiet.com. Two possibilities are:

• Infection with a pathogen that interferes with CYP27B1. Pathogens have evolved ways to interfere with other human proteins in order to suppress the immune response. Since CYP27B1 creates 1,25D which enhances immunity, it would not be a surprise if some pathogen had evolved a way to interfere with CYP27B1.
• Mitochondrial dysfunction. The enzyme coded by CYP27B1 operates in the inner mitochondrial membrane. Only in mitochondria can 1,25D be created. The “mitochondrial theory of aging” holds that mitochondrial decay is the primary cause of aging. Perhaps in elderly people suffering from mitochondrial dysfunction, CYP27B1 does not operate properly.

Conclusion

Whatever the mechanism of CYP27B1 loss-of-function may be, it appears that doubling 25OHD levels remedies much of the loss-of-function within a few weeks.

It might not be amiss for elderly patients and autistic children with symptoms of vitamin D deficiency to experiment with raising 25OHD to twice normal levels. In those with a CYP27B1 defect, this may produce an amazing recovery.

Further recovery might be possible. If the cause is infectious, appropriate antibiotics could help. If the cause is mitochondrial decay, then mitochondrial supplements might help.

The centrality of vitamin D function to optimal aging raises another thought. What if the main cause of aging is not the decay of mitochondria in general, but a specific decay in their support for 1,25D formation in the mitochondrial inner membrane? What if this loss of intracellular 1,25D is widespread among the elderly?

In that case, following Charles’s protocol and raising 25OHD in the elderly might significantly extend lifespans. And improve hair and skin at the same time!

Related Posts

“Vitamin D Dysregulation in Chronic Infectious Diseases,” http://perfecthealthdiet.com/?p=421, August 21, 2010.

References

[1] Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41. http://pmid.us/18525006.

[2] Lou YR et al. 25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. J Steroid Biochem Mol Biol. 2010 Feb 15;118(3):162-70. http://pmid.us/19944755.

[3] Rajasree S et al. Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease. Eur J Epidemiol. 2001;17(6):567-71. http://pmid.us/11949730.

[4] Rowling MJ et al. High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice. J Nutr. 2007 Dec;137(12):2608-15. http://pmid.us/18029472.

[5] Takeda E et al. Vitamin D-dependent rickets type I and type II. Acta Paediatr Jpn. 1997 Aug;39(4):508-13. http://pmid.us/9316302.

[6] Tuohimaa P. Vitamin D and aging. J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):78-84. http://pmid.us/19444937.

[7] Keisala et al. Premature aging in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):91-7. http://pmid.us/19500727.

[8] Cannell JJ. On the aetiology of autism. Acta Paediatr. 2010 Aug;99(8):1128-30. http://pmid.us/20491697. Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-9. http://pmid.us/17920208.

[9] Haussler MR et al. The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the “Fountain of Youth” to mediate healthful aging. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):88-97. http://pmid.us/20227497.

They sometimes exhaust their repertoire of drugs without ever considering using nutritional supplements to support the patient’s immune defense.

An extraordinary illustration comes from New Zealand. It began when Alan Smith, a New Zealand farmer, contracted swine flu:

He caught the Swine Flu (probably while on a fishing trip in Fiji), so badly that his lungs had “white out”, which is to say they were so full of fluid that they didn’t show up on an x-ray. The doctors also said he had got leukemia and he ended up being put on a life support machine.

The doctors told the family the machine should be turned off … [1]

The diagnosis of leukemia is suspicious. Both infections and leukemia lead to “leukocytosis” or a very high white blood cell count. In one case the white blood cells are multiplying to fight the infection, in the other a malignant population is multiplying. The difference is that in leukemia the population is monoclonal, i.e. all the new white blood cells are genetically identical, while in normal people with infections the white blood cells are created with genetic diversity. (Keywords for those who wish to investigate: T-cell antigen repertoire and B-cell immunoglobulin repertoire.)

As subsequent events showed, the leukemia “diagnosis” was mistaken. I wonder if it was made just for “family management” – in order to help persuade the family his case was hopeless and support the recommendation to end life support.

… but the family asked that he be given high dosages of Vitamin C. After a fight (one of many), one of the doctors agreed. Alan began getting better; his lungs showed pockets of air. Then he began to get worse and the family found out the doctors had stopped the Vit C.

Many more fights ensued, the patient getting better while having the Vit C, and getting worse when he was taken off. Alan’s wife describes one of the doctors sitting back in his chair, arms folded, rolling his eyes, looking at the ceiling, telling her that no way could the vitamin C be helping. The family hired a lawyer, forcing the doctors to continue the vit C treatment (albeit in slow dosage, until he got better enough to eat and his wife brought along sachets of large dosage herself for him to take).

Eventually Alan fully recovered, no trace of leukemia even. [1]

He should have been given high doses of vitamin D and iodine as well. Iodine supports leukocyte respiratory bursts of reactive oxygen species which destroy pathogens; vitamin C supports respiratory bursts by recycling glutathione and providing antioxidant protection for leukocytes against their own respiratory bursts, and also supports anti-viral immunity; vitamin D creates antimicrobial peptides that kill many pathogens.

Other possibly beneficial supplements in cases of elevated leukocyte counts due to infection: selenium, to support both glutathione and iodine/thyroid function; iron, for myeloperoxidase (respiratory burst enzyme) and catalase (antioxidant defense); N-acetyl cysteine (for glutathione production) and glutathione; zinc and copper (for the anti-oxidant zinc-copper superoxide dismutase).

Thank goodness the family had the sense to try vitamin C, and that that was enough for him to recover. It would have been a shame if he died for lack of vitamin D and iodine.

New Zealand was a pioneer of socialized medicine in the English-speaking world. Economists say that people respond to incentives; one wonders if the doctors were more motivated to tend to the interests of the bureaucrats who controlled their budgets, than to the health of the family and patient who weren’t paying them. Perhaps “free” medical care has unexpected costs.

References

[1] “Indictment of Our Medical Profession,” New Zealand Conservative, http://nzconservative.blogspot.com/2010/08/indictment-of-our-medical-profession.html; hat tip to Jewel at http://health.groups.yahoo.com/group/infection-cortisol/message/1760.

With the invention of new tools for microbiology over the last 20 years, scientists are for the first time able to study chronic parasitic infections, albeit with difficulty. I mentioned a few weeks ago that this should be the dawn of a “golden era of antimicrobial medicine.” And maybe it is: careful studies are now linking specific pathogens to chronic diseases and discovering the mechanisms by which they cause disease.

A good example of emerging science is the progress made since 2002 in understanding a retrovirus family that is now firmly linked to cancer and chronic fatigue syndrome and may soon be linked to other diseases.

Beginning of the Story:  Human Anti-Viral Immunity and Chronic Fatigue Syndrome

Our story begins back in the 1970s with studies of the role of interferons in defending human cells against viruses. Interferons are a key part of the immune defense against intracellular pathogens – the ones that cause most human chronic diseases.

Following the effects of interferons, researchers discovered an enzyme known as ribonuclease L (RNase L). RNase L is upregulated by interferons and its function is to degrade RNA, both viral and human, to stop viral replication. [1]

Aside: High levels of RNase L destroy so much human RNA that the cell dies. This is probably adaptive for the host, since cell apoptosis also kills many pathogens within. However, it shortens lifespan. RNase L knockout mice have extended lifespans. [1]

In 1997, RNase L was found to be strongly upregulated in chronic fatigue syndrome patients. [2] This showed that chronic fatigue patients usually have viral infections. Whether the viruses were causing chronic fatigue, or just “hitchhiking” with a disease that suppressed the immune system (perhaps via a bacterial infection?), remained an open question.

A Link Between RNase L and Prostate Cancer

By the early 2000s it was established that a common (allele frequency 35%) gene mutation, the “R462Q” mutation which substitutes a glutamine for an arginine in the “hereditary prostate cancer 1” locus, raised the risk of prostate cancer. A man with two copies of this mutation has twice the risk of prostate cancer; one copy raises the risk by 50%. About 13% of prostate cancer cases were attributable to this mutation. [1, 3, 4]

It was important, therefore, to determine which protein this locus coded for. A breakthrough finding, made in 2002, was that the “hereditary prostate cancer 1” locus was the gene for RNase L. [5]

It was soon shown that the R462Q mutation decreased the effectiveness of RNase L at cleaving viral RNA. This placed prostate cancer in a new light: it implied that an unknown virus against which RNase L defends was a probable cause of prostate cancer. When RNase L function was impaired by the R462Q mutation, the infection became more virulent, and prostate cancer rates were higher. [1]

The search for this unknown virus was on.

The discovery of “xenotropic murine leukemia virus-related virus” (XMRV)

The strategy was basically to take prostate tumors and search for viral RNA, looking for viruses that were most common in patients who had the double R462Q mutation.

In 2006 one of these searches yielded fruit.  A new gamma retrovirus was found in 8 of 20 prostate cancer patients with double R462Q mutations, but only 1 of 66 patients without the double mutation. [6]

This gamma retrovirus shared a lot of RNA with a family known as the xenotropic murine leukemia viruses (MuLVs). It was dubbed “xenotropic murine leukemia virus-related virus” (XMRV). Despite the sound, it is not a murine (mouse) leukemia virus; it merely shares a lot of nucleic acids with those viruses.

Back to chronic fatigue syndrome

In 2009 a paper was published in Science reporting that XMRV was found in peripheral blood cells of 67% of chronic fatigue patients but only 3.7% of healthy controls. [7] This study was done by a group at the Whittemore Peterson Institute in Reno, Nevada.

Aside:  The Whittemore Peterson Institute has a nice Q&A about this virus and its role in chronic fatigue syndrome here.

A number of researchers tried and failed to reproduce these results. For instance, a group from the Centers for Disease Control failed to detect XMRV proteins in 51 chronic fatigue and 53 healthy patients. [8]

Perhaps proteins are just not the right molecules for detecting this virus. A new paper has just appeared that links XMRV more strongly than ever to chronic fatigue. It looked at DNA for viral genes inserted into the human genome and found XMRV sequences in 86.5% of chronic fatigue patients but only 6.8% of controls. [9] This paper was held back from publication since June because of its conflict with the CDC paper (see “Why I Delayed XMRV Paper”), but has now been released.

These percentages are impressive and, if they hold up, would seem to make it unlikely that XMRV is merely a “passenger” virus hitchhiking on a suppressed immune system. It may be causal for chronic fatigue.

Will anti-retroviral therapies be effective?

Clinical trials are extremely expensive and the drug companies seem to be waiting for XMRV to be proven as the cause of chronic fatigue before undertaking trials. From the Wall Street Journal:

Norbert Bischofberger, chief scientific officer at Gilead Sciences Inc., the leading maker of HIV drugs, said the company might consider a small pilot trial but would like to see stronger evidence that the viruses cause CFS before launching a large trial. Still, “I’m very open, and this would be a great opportunity,” he said.

A spokesman for Merck & Co., another major manufacturer of HIV drugs, said: “A clinical trial program would be possible to develop only after further substantial evidence of an association with CFS.” [10]

But some aren’t waiting for trials. Anti-retroviral drugs developed for AIDS are being prescribed off-label:

Jamie Deckoff-Jones, 56 years old, a doctor and CFS patient in New Mexico, has been blogging about her experiences and those of her 20-year-old daughter. Both tested positive for XMRV and are taking a combination of three anti-retrovirals.

Dr. Deckoff-Jones said a year ago she could only get up for short periods during the day. After five months on the drugs, she flew last week to Reno for an XMRV conference. Her daughter was able to go to a party and is enrolling in community college. “This is all very new, and there is no way to know if improvement will continue,” Dr. Deckoff-Jones wrote in an email, “but we appear to be on an uphill course.” [10]

Chronic fatigue patients are celebrating the progress:

Many [CFS patients] were ecstatic at news that the second study was being published.

“We’re really hoping this will blow the lid off,” said Mary Schweitzer, a historian who has written and spoken about having the illness. “Patients are hopeful that now the disease itself might be treated seriously, that they’ll be treated seriously, and that there might be some solution.” [11]

It’s sad that for decades many haven’t taken chronic diseases seriously. The absence of a known cause reflected only the lack, until recently, of microbiological tools capable of detecting and characterizing intracellular pathogens.

Had doctors taken these diseases seriously, the accumulating evidence that these were chronic infectious diseases caused by intracellular parasites might have encouraged them to look for the sort of dietary and nutritional therapies for chronic disease that we advocate on this blog. Though diet and nutrition by themselves will probably not cure these diseases, they can greatly slow disease progression and improve the odds of a cure.

A new name for XMRV: Human Gamma Retrovirus

The Whittemore Peterson Institute recently hosted the first official scientific symposium on XMRV. Dr. Joseph J. Burrascano reported from the symposium:

We formed a working group to be in constant touch and we plan to meet regularly because advances are coming so rapidly.

Big news that everyone should know and adopt is that we have proposed a name change for the virus.

This virus is a human, not mouse virus, and it is the first and so far only gamma-retrovirus known to infect people. Also, it is clearly not an “endogenous” retrovirus (one that is present in all genomes due to ancient infection).

Because of all of this, and because of the desire to begin on the right track, the new name of the virus is HGRV- Human Gamma Retro Virus. The illness caused by this infection is named HGRAD- Human Gamma Retrovirus Associated Disease.

We plan to announce this at the upcoming NIH retroviral conference this September.

Definitely stay tuned- the volume of new and important information about this virus and its disease associations is increasing rapidly and in my opinion should be a concern to every patient with chronic neuro-immune diseases, including those with chronic Lyme. [12]

It sounds like some exciting findings may be on the way.

Conclusion

This case is a fascinating illustration of the twisting turns that scientific research can take. The early discovery of a link between anti-viral immunity and prostate cancer may now lead to a cure for chronic fatigue syndrome. At least, we can hope so.

As one of the pioneers, Dr. Robert Silverman, describes it,

One of the remarkable aspects of being a scientist, is that you never know where your scientific journey will lead. [1]

Science takes a lot of patience, diligence, and persistence. It’s gratifying when all that work is rewarded by discovery.

References

[1] Silverman RH. A scientific journey through the 2-5A/RNase L system. Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):381-8. http://pmid.us/17681844.

[2] Suhadolnik RJ et al. Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res. 1997 Jul;17(7):377-85. http://pmid.us/9243369.

[3] Silverman RH. Implications for RNase L in prostate cancer biology. Biochemistry. 2003 Feb 25;42(7):1805-12. http://pmid.us/12590567.

[4] Casey G et al. RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet. 2002 Dec;32(4):581-3. http://pmid.us/12415269.

[5] Carpten J et al. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet. 2002 Feb;30(2):181-4. http://pmid.us/11799394.

[6] Urisman A et al. Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog. 2006 Mar;2(3):e25. http://pmid.us/16609730.

[7] Lombardi VC et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. http://pmid.us/19815723.

[8] Switzer WM et al. Absence of evidence of xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the United States. Retrovirology. 2010 Jul 1;7:57. http://pmid.us/20594299.

[9] Lo S et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. PNAS Epub before print August 23, 2010. http://www.pnas.org/content/early/2010/08/16/1006901107.abstract.

[10] Amy Dockser Marcus, “New Hope in Chronic Fatigue Fight,” Wall Street Journal, Aug 23, 2010, http://online.wsj.com/article/SB10001424052748703846604575447744076968322.html.

[11] David Tuller, “Study Links Chronic Fatigue to Virus Class,” New York Times, Aug 23, 2010, http://www.nytimes.com/2010/08/24/health/research/24fatigue.html.

 [12] http://www.forums.aboutmecfs.org/showthread.php?7001-News-from-WPI-symposium-Name-change-to-be-proposed-for-XMRV (hat tip http://health.groups.yahoo.com/group/infection-cortisol/message/1753).

24 ng/ml is well below the optimal level for healthy people of 40 ng/ml. When a healthy person supplements vitamin D, the serum 25(OH)D level usually rises linearly with dose up to about 40 ng/ml, then it rises very slowly thereafter as the body tries to keep 25(OH)D from rising by putting vitamin D into storage.

So it was natural for qualia to expect his serum 25(OH)D level to rise when he doubled his dose.

But it didn’t. The stability of his 25(OH)D levels suggests that his body has reached an equilibrium at 24 ng/ml. Instead of plateauing at 40 ng/ml with abundant vitamin D3 as a healthy person would, he is plateauing at a lower level.

Why does that happen?

Well, I don’t know. But I would like to provide qualia with a little bit of background, because this could be a clue that helps diagnose his condition and optimize treatments.

Normal vitamin D regulation strictly controls 1,25D levels

I suggested in the comment thread that qualia get his 1,25D levels measured as well as 25(OH)D.

Levels of 1,25D are not routinely measured, even in scientific studies, because they rarely vary. Blood levels of 1,25D control calcium homeostasis and are tightly regulated. In healthy people, as vitamin D intake rises from zero, serum 1,25D levels shoot up to normal levels before 25(OH)D levels reach 12 ng/ml. They then stay in a normal range no matter how high 25(OH)D levels rise. The kidney is the primary controller of blood 1,25D levels. The normal range is about 16 to 42 pg/ml (42 to 110 pmol/L).

While all human cells can convert 25(OH)D to 1,25D, most cannot release 1,25D into the blood. 25(OH)D freely crosses cell membranes and maintains the same level throughout the body; but 1,25D does not cross membranes. This allows every cell in the body to “personalize” its 1,25D levels to its own needs.

Both 25(OH)D and 1,25D are active ligands for the Vitamin D Receptor (VDR), a nuclear receptor.  [1] When either 25(OH)D or 1,25D binds to the VDR, the compound is imported into the nucleus, where it combines with a vitamin A-activated Retinoid X-Receptor (RXR) to form a transcription factor which, among other roles, upregulates production of antimicrobial peptides (AMPs) that are crucial for cellular defense against intracellular pathogens.

The difference between 25(OH)D and 1,25D is that 1,25D is about fifty-fold more likely to bind to the VDR than 25(OH)D. So by converting more 25(OH)D to 1,25D, cells can upregulate their VDR activation and upregulate their immune defense against pathogens. Meanwhile, uninfected cells can keep their 1,25D levels low. Across human cells, there is a thousand-fold variation in the rate of conversion of 25(OH)D to 1,25D. [1]

In chronic infectious diseases, blood 1,25D is dysregulated

However, in people with chronic infectious diseases, 1,25D levels range all over the map, and are largely uncorrelated with 25(OH)D levels.  Here is a scatter plot from a paper by Dr. Greg Blaney [2]:

The patients in this sample were 100 chronic disease patients: 29 with fibromyalgia, 27 with chronic fatigue syndrome, 12 with post-treatment Lyme Disease, 9 with metabolic disease, 6 with osteoarthritis, 4 with irritable bowel syndrome, 4 with psoriatic arthritis, 3 with multiple sclerosis, 3 with seronegative arthritis, and 27 with other diseases.

Probably all of these diseases are caused by chronic parasitic infections.

A few things to note from this plot: (1) 25OHD levels in a lot of chronic disease patients cluster around the 61 nmol/L level that qualia has; and (2) most chronic disease patients have 1,25D levels well above the normal range, even though their 25OHD levels are mostly below the optimal level in healthy people.

What Causes 1,25D Dysregulation?

Here’s where we get into speculation. There just hasn’t been research exploring this question. Researchers are only just realizing that these diseases are infectious in origin and that vitamin-D-mediated innate immunity is critical to the intracellular immune defense.

Rather than speculate, I’m just going to mention a couple of possibilities.

First, in granulomatous diseases like sarcoidosis, it’s common to have low 25(OH)D and very high 1,25D. Granulomas are nodules where immune cells have been unable to eliminate some foreign matter and instead have built a barrier around it that walls it off from the body.  Granulomas often release 1,25D to the body. Some other granulomatous diseases: 

• Tuberculosis
• Leprosy
• Schistosomiasis
• Histoplasmosis
• Cryptococcosis
• Crohn’s disease

These are all infectious diseases, some of them protozoal in origin.

Second, nearly all human pathogens manufacture proteins or RNA that interfere with the innate immune response. Some are known to interfere with the VDR or with other aspects of vitamin D biology. (The HIV virus blocks the VDR entirely, one reason why it predisposes AIDS patients to infections.) It’s possible that vitamin D dysregulation is brought about by direct pathogen actions to disrupt cellular vitamin D pathways.

Conclusion

The only thing we can conclude with confidence from qualia’s vitamin D tests is that he must have a chronic infectious disease … but he knew that already.

Qualia would be best served by getting advice from an infectious disease specialist with experience in chronic diseases. Such a doctor might be able to narrow down the diagnosis. A diagnosis would help determine which antibiotics might be appropriate to help fight the infection.

Until a doctor’s diagnosis or qualia’s personal experience indicates otherwise, it’s probably prudent to continue with a reasonable intake of vitamin D and to increase iodine as quickly as possible. (Even this is not certain: the standard advice is to minimize vitamin D in granulomatous diseases.) Other infection-fighting supplements, like vitamin C, N-acetylcysteine, and glutathione are likely to be helpful also.

Finally, I always recommend that anyone with a chronic disease find a good discussion forum, like the one at http://cpnhelp.org, and try to find people with similar disease histories and learn from their experiences.

Best of luck, qualia, and please keep us posted.

References

[1] Lou YR et al. 25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. J Steroid Biochem Mol Biol. 2010 Feb 15;118(3):162-70. http://pmid.us/19944755.

[2] Blaney GP et al. Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Ann N Y Acad Sci. 2009 Sep;1173:384-90. http://pmid.us/19758177.

We’ve mentioned previously the example of statin research. Statin studies are generally performed by cardiologists and in the U.S., many statin studies reported only heart attacks and other cardiovascular events as endpoints, not total mortality, cancer, or infectious disease. This method of evaluating drugs would show a lethal neurotoxin to be the best cardiac treatment ever:  In the neurotoxin group not a single patient would die of a heart attack!

A similar myopia has occurred in osteoporosis research, where doctors have focused on the effect of calcium supplements on bone density or fracture rates but often do not evaluate the effect of the supplements on overall health.

But other effects have to be considered, given that:

• Calcification of coronary arteries may be the best single indicator of heart attack risk. [1]
• In the Nurse’s Health Study, supplementation of calcium increased the risk of calcium oxalate kidney stones by 20%. [2]
• Calcium is a strong promoter of biofilm formation in most pathogenic bacterial species. [3] It also likely promotes formation of Candida albicans (fungal) biofilms. As a result, it can aggravate bowel disorders and infectious diseases.

Clearly, calcium in the wrong places – a problem that could be exacerbated by calcium supplementation – is a major health risk.

What causes calcium to go in the wrong places? Deficiencies of vitamin D and vitamin K2 are common reasons. Deficiencies of both are widespread. Vitamin K2 deficiency is a known cause of vascular calcification.

A few years ago, a group of New Zealand researchers conducted a randomized clinical trial that found that over five years, older women taking calcium supplements doubled their risk of heart attack compared to women taking a placebo. [4]

Now, the same group has conducted a systematic review of calcium supplementation studies which confirms the link between calcium supplementation and heart attacks. Dr. Mark Bolland of the University of Auckland, New Zealand, and colleagues report that calcium supplementation increases the risk of heart attack by 31%, the risk of stroke by 20% and the risk of death by 9%. [5]

In an accompanying editorial, Dr. John Cleland writes:

Calcium supplements, given alone, … are ineffective in reducing the risk of fractures and might even increase risk, they might increase the risk of cardiovascular events, and they do not reduce mortality. They seem to be unnecessary in adults with an adequate diet. Given the uncertain benefits of calcium supplements, any level of risk is unwarranted. [6]

We concur. A healthy diet, including dairy and green leafy vegetables, not to mention a daily multivitamin (ours contains 200 mg calcium), should provide a sufficiency of calcium as long as vitamin D levels are normal. If you’re worried about bone health, supplement with vitamins D, K2, and magnesium citrate – not calcium.

[1] Budoff MJ et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860-1870. http://pmid.us/17481445. 

[2] Curhan GC et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997 Apr 1;126(7):497-504. http://pmid.us/9092314.

[3] Kierek K, Watnick PI. The Vibrio cholerae O139 O-antigen polysaccharide is essential for Ca2+-dependent biofilm development in sea water. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14357-62. http://pmid.us/14614140.  Geesey GG et al. Influence of calcium and other cations on surface adhesion of bacteria and diatoms: a review. Biofouling 2000; 15:195–205.

[4] Bolland MJ et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008 Feb 2;336(7638):262-6. http://pmid.us/18198394.

[5] Bolland MJ et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010 Jul 29;341:c3691. doi: 10.1136/bmj.c3691. http://pmid.us/20671013.

[6] Cleland JG et al. Calcium supplements in people with osteoporosis. BMJ. 2010 Jul 29;341:c3856. http://pmid.us/20671014.

There are an estimated 600 supercentenarians in the world, whereas the number of centenarians probably exceeds 600,000. There are about 100,000 centenarians in the US, 40,000 in Japan, and 8,500 in England and Wales. [1] Meanwhile, only about a dozen people in the world may currently be age 115 or older. The oldest person who ever lived, Jeanne Calment, reached age 122. [2]

As I mentioned yesterday, I have a Google Alert for centenarian stories and have been reading about them for some time. One thing I’ve found is that most centenarians don’t seem to think very much about their diets (which protects them from the food pyramid!), but supercentenarians tend to be very picky about what they eat.  Supercentenarian diets come in two basic flavors:

1)      Calorie-restriction and intermittent fasting.

2)      High (saturated and monounsaturated) fat low-carb diets.

We present some supercentenarian stories in the diet book; here are a few. First, some fat lovers.

Jeanne Calment “ascribed her longevity and relatively youthful appearance for her age to olive oil, which she said she poured on all her food and rubbed onto her skin” [2]. She also drank wine and ate chocolate every day. Olive oil, wine, and chocolate — you can’t get much healthier than that, as long as you get some vitamins on the side, and don’t let too much sugar in.

Gertrude Baines of Los Angeles lived to 115 on extremely healthy diet – bacon, chicken, and ice cream:

Gertrude Baines, who lived to be the world’s oldest person on a steady diet of crispy bacon, fried chicken and ice cream, died Friday at a nursing home. She was 115. [3]

When Edna Parker of Indiana died at age 115, Governor Mitch Daniels was impressed by her diet:

Parker especially enjoyed eggs, sausage, bacon and fried chicken. “I guess we’ll have to rethink lard,” Daniels quipped after hearing about her high-fat diet. [4]

The other longevity strategy is calorie restriction. Among the pioneers was Luigi Cornaro, a medieval Venetian nobleman who lived to 98, maybe over 100. Wikipedia explains:

Finding himself near death at the age of forty, Cornaro modified his eating habits on the advice of his doctors and began to adhere on a calorie restriction diet. Twelve ounces of solid food and fourteen ounces of wine was the daily allowance he allowed for himself initially. He later reduced his daily food intake to no more solid meat than an egg.

His first treatise was written when he was eighty-three, and its English translation, often referred to today under the title The Sure and Certain Method of Attaining a Long and Healthful Life, went through numerous editions. [5]

Intermittent fasting (say, confining food to an 8-hour window each day) is a great way to implement calorie restriction.  A practitioner is Walter Breunig of Great Falls, Montana:

So what does the world’s oldest man eat? The answer is not much, at least not too much.

Walter Breuning, who turned 113 on Monday, eats just two meals a day and has done so for the past 35 years.

“I think you should push back from the table when you’re still hungry,” Breuning said.

At 5 foot 8, (“I shrunk a little,” he admitted) and 125 pounds, Breuning limits himself to a big breakfast and lunch every day and no supper….

“You get in the habit of not eating at night, and you realize how good you feel. If you could just tell people not to eat so darn much.”…

And for his birthday lunch he got his favorite: liver and onions. [6]

I like that: liver and onions. Nutritious and fatty. You don’t find supercentenarians eating cake on their birthdays!

Fasting, however, can be taken too far. Sogen Kato’s strategy was ill-conceived:

Tokyo’s oldest man is no longer the city’s reigning centenarian….

Officials grew suspicious earlier this year when they attempted to visit [Sogen] Kato, who was to turn 111 last month. His family refused to let anyone in to see him, and repeatedly chased welfare officials away.

Eventually returning with police, the welfare officials discovered a mummified corpse, believed to be Kato, lying on a bed in his underwear and pajamas.

He is believed to have died in 1980 at the age of 81.

Kato, born in 1899, had long been believed to be one of the world’s oldest people.

Police suspect Kato’s family — his 79-year-old daughter and two grandchildren — had hidden Kato’s death in order to keep collecting his pension. They reportedly received upwards of 9.5 million yen (about $190,000).

The family, however, has an alibi: they claim Kato had “confined himself in his room more than 30 years ago and became a living Buddha,” according to a report by Jiji Press. [7]

Thirty-year fasts rarely work. If you do decide to become a living Buddha, ask for some bacon, eggs, liver, wine, and chocolate with your Zen.

References

[1] Max Planck Institute for Demographic Research; http://www.csmonitor.com/World/2010/0810/Supercentenarians-around-the-world/Italy;  http://en.wikipedia.org/wiki/Centenarian.

[2] http://en.wikipedia.org/wiki/Jeanne_Calment.

[3] “World’s Oldest Person Dies in L.A. at 115,” MSNBC.com, Sept. 11, 2009.

[4] Elaine Woo, “Edna Parker dies at 115; former teacher was world’s oldest person,” Los Angeles Times, Nov. 28, 2008.

[5] http://en.wikipedia.org/wiki/Luigi_Cornaro.

[6] Sydne George, “Two-meal diet aids in oldest man’s longevity,” USA Today, Sept 24, 2009.

[7] Michael Sheridan, “Officials learn Tokyo’s oldest man, Sogen Kato, actually died 30 years ago; family kept body hidden,” New York Daily News, August 2, 2010.

I had some fun with a nutritional brain teaser not long ago. The point of it was that almost any food – including cookies, ice cream, and potato chips – can be healthy if the ingredients are good, and any food will be unhealthy if the ingredients are toxic. Unfortunately, most prepared foods in supermarkets, and many restaurant foods, are made with toxic ingredients. It’s a sad commentary on today’s world; but if you want a long life, it’s almost essential to cook your own food.

I get a daily Google alert with news stories about centenarians. One of the most common features is that centenarians like to cook. The following three stories all came on the same day:

Via the Leesburg (Florida) Daily Commercial:

Great-great grandmother Mary D. Nix, 101, has a zest for life and believes it’s vital to live by the Golden Rule.

“I’m going to keep on living,” she said….

Born on July 28, 1909, in Leary, Ga., she married her husband, Elijah, when she was 16. The couple lived in Tangerine and Nix worked for more than 40 years as a domestic housekeeper.

“She worked for rich people all of her life, keeping the houses cleaned, their dinners cooked, and children fed,” said Thelma Hayes Wooden, the second oldest of Nix’s 17 grandchildren.

“She still thinks a woman’s job is in the kitchen,” Wooden said with a chuckle, recalling her grandmother would share advice with her family and others in her care.

Via the Burton (Staffordshire, UK) Mail:

The birthday girl said she used to enjoy cooking, knitting, sewing and gardening when she was younger.

Mrs Wright said: “I enjoy life very much and especially living in the home….

 “I’ve had so many highlights in my life and I couldn’t tell you what the secret to a long and happy life is, as I’m not sure.”

Via the New Haven (Connecticut) Register:

Her other son, Anthony Monaco of Denver, Colo., said his mother was feisty, a great cook and a hard worker. “She and my dad did a very good job of putting food on the table and raising us,” he said. “She would walk two miles from work to home each night, stop at the store and gather all the ingredients for that night’s dinner, come home, make dinner and get out the ironing board.

“She worked hard all day and pretty much all night. She also was a devout Catholic.”
Monaco died July 12 at age 100….

In her spare time, she liked to play cards, crochet, knit, cook, garden, walk, go to the casinos, dance and listen to Italian music.

Another common feature of centenarians is that they are cheerful and highly sociable. Centenarians always seem to have many friends.

Sociability does not always imply marriage: a surprisingly large number of centenarian women have never married. But marriage is no bar to longevity, as Wook Kundor of Malaysia shows:

Centena­rian Wook Kundor is all alone again.

Her husband Mohd Noor Musa, who is seven decades her junior, was rearrested for a drug-related offence on Sunday….

“He reneged on his promise not to indulge in drugs. But I can’t live without him,” she said when met here yesterday….

“I don’t know what is wrong with him. Probably he is bored without a steady job,” she said.

Wook Kundor said police had told her that her husband had tested positive for heroin….

She married Mohd Noor, her 23rd husband, five years ago.

Perhaps what makes a centenarian is this: “You can go to extremes with impossible schemes / You can laugh when your dreams fall apart at the seams / And life gets more exciting with each passing day / And love is either in your heart or on its way / Don’t you know that it’s worth every treasure on earth / To be young at heart.”

Various bloggers have discussed their proposal, and if you are interested here are some links:

• Tom Naughton (Fat Head)
• Stephan Guyenet (Whole Health Source)
• Dr. John Briffa

We rarely discuss drugs, since we’re diet and nutrition focused, but briefly, statins should be avoided because they do a mix of benefits and harms, of which the benefits are minor and can be better achieved by other means, and the harms can be immense:

• Coenzyme Q10 deficiencies impairing mitochondrial function and producing potentially life-threatening muscle weakness (myopathy).
• Cholesterol deficiencies impairing cell movement, cell division, and wound healing and increasing risk of infectious disease and cancer.
• A myriad of other effects, including liver damage, kidney damage, and cataracts.

It appears that the benefits of statins are achieved mainly through two mechanisms – an elevation of vitamin D synthesis and a mild anti-inflammatory effect. (Cholesterol-lowering drugs which lack these effects have proven to be highly poisonous.) Normalizing vitamin D levels through sunshine and supplements would eliminate the first benefit; eating a diet low in food toxins would eliminate the second benefit. So for people practicing healthy diets, there is likely to be no benefit from statins at all, and much harm.

It’s telling that clinical trials conducted since trial regulations were tightened a few years ago have failed to show any benefit from statins. [2] Earlier trials were biased in various ways, including in many cases a failure to report overall mortality or deaths from infectious disease and cancer, and a severe publication bias in which trials producing negative effects were suppressed.

Meanwhile simple, inexpensive steps like supplementation can have much bigger health benefits than statins. Normalizing vitamin D levels can cut mortality in half [3, 4] and supplementing vitamin K2 can reduce mortality by 26%. [5]

So, if we don’t normally discuss drugs, what prompted this post?  My eye was caught by Stephan’s observation that farm subsidy modifications could greatly improve public health:

Rather than giving people statins along with their Big Mac, why don’t we change the incentive structure that artificially favors the Big Mac, french fries and soft drink? If it weren’t for corn, soybean and wheat subsidies, fast food wouldn’t be so cheap. Neither would any other processed food. Fresh, whole food would be price competitive with industrial food, particularly if we applied the grain subsidies to more wholesome foods.

I’ve long advocated this change myself. It’s ironic that the US government managed to pick the most toxic foods – wheat, corn, and soybeans – for its agricultural subsidies. 

It’s often pointed out that U.S. longevity is worse than would be expected based on our GDP. Here’s a chart from gapminder.org – click for a legible version:

If you fit a curve and measure distance beneath the curve, among rich nations only Brunei, Qatar, and maybe Luxembourg and Liechtenstein perform worse than the US. Americans die years earlier than we ought.

The reason for this is probably mainly our agricultural subsidies and the high intake of toxic foods they have engendered. (Our high intake of health-impairing drugs like statins may also contribute.) As I commented on Stephan’s blog:

If we ate rice instead of wheat, butter instead of soybean oil, and drank tea instead of corn syrup, Americans might be the longest-lived people in the world.

Diet and nutrition are the keys to health, yet they are the ugly stepchildren of American medicine. Drugs remain the favored and spoiled son, producing little but beloved.

References

[1] Ferenczi EA et al. Can a Statin Neutralize the Cardiovascular Risk of Unhealthy Dietary Choices? Am J Cardiol. 2010 Aug 15;106(4):587-592. http://pmid.us/20691321.

[2] de Lorgeril M. Disappointing recent cholesterol-lowering drug trials: is it not time for a full reappraisal of the cholesterol theory? World Rev Nutr Diet. 2009;100:80-9. http://pmid.us/19696530.

[3] Dobnig H et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008 Jun 23;168(12):1340-9. http://pmid.us/18574092.

[4] Pilz S et al. Vitamin D and mortality in older men and women. Clin Endocrinol (Oxf). 2009 Nov;71(5):666-72. http://pmid.us/19226272.

[5] Geleijnse JM et al. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. http://pmid.us/15514282.

LynMarie Daye brings news of a nurse who failed to solve the puzzler. The nurse tried to discourage a diabetic patient from eating ice cream – perhaps a wise move, considering the levels of sugar in most commercial ice cream; but only if better, not worse, foods replace the ice cream. The hospital administration reprimanded her for not providing the ice cream with a smile.

If I am going to give people what they want with a smile instead of what they need with understanding and caring, then I’ll flip burgers. I have ALWAYS greeted my patients (yes patients) with a smile, a caring hand on the shoulder if they allow and carefully explained what, why, and how. Lately I left a bedside with confidence that while not pleased with their situation, they were comfortable with it. An hour later I’m being called into the charge nurse’s office being chewed out for being mean and/or rude to the patient and/or the family! I did my nursing duty, I brought them that extra helping of ice cream with a teaching that this may not be their best choice for a diabetic and perhaps they would do better with the apple slices or sugar free cake I also brought along. But how rude of me to suggest such things! The “client” knows what is best for them, I’m told.

The nurse is well-intentioned but look what she recommends over ice cream – the most fructose-rich of fruits, the apple; and a cake full of toxic wheat proteins. Both these foods provide all calories as carbs, precisely the macronutrient that diabetics are least able to handle. When her diabetic finished the apple slices and was still hungry, would she bring more apples and cake?  At least the ice cream provides egg yolks and dairy fats that satiate appetite and displace carbs from the diet.

I wish I could say the hospital reprimanded her for faulty diet advice. Unfortunately, it seems the hospital’s only concern was the patient’s pleasure. It appears the hospital would be content to help patients poison themselves, if that would increase customer satisfaction.

They say you can lead a horse to water but can’t make him drink.  When it comes to diet, the medical industry has lost the way to the water and has given up leading. Frankly, I’d rather be a horse than a hospital patient.