Thursday, 5 May 2016

Low Bone Density in Autism and Brain Calcification (Bone-Vascular Axis + Altered Calcium Homeostasis), – a role for Vitamin K2, or something more potent?

Today’s post with a long tittle is a spin-off from looking at the health benefits of the Mediterranean Diet.  This often quoted diet really does make you live longer and healthier; scientists are again trying to understand exactly why.  This sent me looking at various things, one of which was vitamin k, which is abundant in the Mediterranean diet.  It turns out that another healthy diet, one found in Japan, may have incorporated an even better source of this vitamin, since it is high in vitamin K2 rather than K1.

I thought this post would just end up being about general health, rather than autism specifically, but as I did more digging it seems highly credible that some people’s autism could be improved simply by adjusting their calcium homeostasis.

This will not come as a surprise to one of our readers who discovered that giving oral calcium supplements to her son with Asperger’s triggered a major regression towards Classic autism. Fortunately it was reversed by stopping the supplementation.

You likely have an older relative with osteoporosis, which is caused by decreased bone density.  Osteoporosis is defined as a bone density of 2.5 standard deviations below that of a young adult.

Osteoporosis is a condition caused by loss of calcium homeostasis, meaning that bones are losing too much calcium to the blood.  Not surprisingly this calcium has to go somewhere and researchers have come up with the idea of the bone-vascular axis, to explain that this calcium ends up causing vascular calcification, particularly in the heart.

Because so many Americans have heart disease, the condition is very well funded and studied.  You can measure the level of calcium deposits (calcification) in the heart and you can measure bone density.

Many people with osteoporosis (loss of calcium in the bones) suffer from vascular calcification.

People who have a diet high in vitamin K and particularly vitamin K2 have much lower incidence of diseases of the bone-vascular axis and therefore live longer.

In Japan high dose vitamin K2 is a registered drug to treat osteoporosis.  In the West K2 exists as a drug, but not for osteoporosis or calcification.

In the rest of the world it is available as a supplement in very low doses.

In the Western world of evidence-based medicine it appears Japanese evidence does not count.  This is not the first time I have encountered this.

In the west people with osteoporosis might be prescribed calcium supplements that have added vitamin D to promote absorption.

Fortunately there also some interesting drugs that have been developed to affect calcium homeostasis.  Some are now cheap generics.

Bone-vascular axis in Autism

This is an autism blog, so we already know that in autism there is excess calcium found in those samples held in brain banks.

There was also a very recent study:-

Background: Intracranial calcifications are observed in many diseases including those with viral and bacterial infections, vascular pathology, toxic injury, brain tumors, teratomas, lissencephaly, in children with Fahr’s disease, and very often in parasitic infections (Rabbitt et al 1969).
Objectives: Our neuropathological studies of autistic subjects brains have revealed the presence of dystrophic changes with calcification. The aim of this study was to determine the prevalence of this type of encephalopathy in autistic and control cohorts.

Methods: The brain hemispheres of 13 autistic and 14 control subjects 4 to 64 years of age were fixed in 10% formalin, dehydrated and embedded in celloidin and cut into 200 μm- or 50 μm-thick coronal serial sections
Results: Dystrophy with calcification was found in all of the 13 autistic and 14 control brains examined. Dystrophic changes disrupt the continuity of the cortical ribbon and white matter in the frontal, temporal and occipital lobes but only on the lateral side of the brain. The pathology spreads from the leptomeningeal vessels to the cortex and white matter and was detectable by postmortem MRI and histopathological examination. Microscopic examination revealed linear dystrophic lesions free of neurons but with signs of neuronal degeneration at the border between the dystrophic and normal cortex. There was no sign of activation of astrocytes or macrophages within the dystrophic and adjacent brain tissue. The dominant component of the dystrophic lesions was calcium deposits.

Conclusions: Similar morphology of lesions in control and autistic subjects 4 to 64 years of age suggests that dystrophic calcifications undergo relatively limited modifications with age. However, the presence of degenerated neurons and vessels with degenerated smooth muscle cells in the border zone between the lesion and cortex suggests the process of brain tissue damage continues to progress decades after the original causative events. Multifocal dystrophy with calcification in all the examined brains of autistic and control subjects reflects a common pathological mechanism with yet undetermined subclinical or clinical manifestations.

What about reduced bone density in autism?  Well I thought nobody would have looked, but they have.

Studies Link Autism to Low Bone Density and Increased Fractures

The increased risk was greatest among girls and women affected by autism spectrum disorder:
* Girls with autism had eight times the hip-fracture rate of other girls.
* Women with the disorder had ten times the rate of spinal fracture of other women.
* Boys with autism had double the hip-fracture rate of other boys.
* Men and women with autism (ages 23 to 50) had nearly 12 times the hip fracture rate of other adults.
* Women with autism also had double the rate of arm, wrist and hand fractures.

Bone Density in Peripubertal Boys with Autism Spectrum Disorders

Brief Report: Bone Fractures in Children and Adults with Autism Spectrum Disorders

So it looks like more severe autism (autistic girls have 8 times higher fracture rate) in particular is linked with reduced bone density. Girls with autism tend to have more severe autism, at least until recently. This is what you would have expected, the more severe the autism the more disturbed the calcium homeostasis and likely bone-vascular axis.

Is there excess calcium in the hearts of people with autism? I guess nobody thought to look.  People will severe autism tend not to live into old age and so data will be limited.

Since you can study and measure calcification non-invasively, some researcher with time on his/her hands might want to correlate reduced bone density with calcification in the brain/heart.

Given the critical role calcium signaling plays in signaling within the brain, it is clear that excess physical calcium has the potential to disturb all the finely balance flows of Ca2+ ions that control many aspects of brain function.

In particular the excess Ca2+ affects mitochondria, which is known to be disturbed in many people with autism.  The mechanism here is the mitochondrial aspartate/ glutamate carrier (AGC).

Altered calcium homeostasis in autism-spectrum disorders: Evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient–control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/ glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca 2+). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca 2+ chelator ethylene glycol tetraacetic acid; neocortical Ca 2+ levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca 2+ -containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca 2+ levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca 2+ homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

Other diseases of brain calcification

There are conditions known to be caused by brain calcification.

Vascular Calcification

Vascular Calcification

Clinically, vascular calcification is now accepted as a valuable predictor of coronary heart disease.  Achieving control over this process requires understanding mechanisms in the context of a tightly controlled regulatory network, with multiple, nested feedback loops and cross talk between organ systems, in the realm of control theory. Thus, treatments for osteoporosis such as calcitriol, estradiol, bisphosphonates, calcium supplements, and intermittent PTH are likely to affect vascular calcification, and, conversely, many treatments for cardiovascular disease such as statins, antioxidants, hormone replacement therapy, angiotensin-converting enzyme inhibitors, fish oils, and calcium channel blockers may affect bone health. As we develop and use treatments for cardiovascular and skeletal diseases, we must give serious consideration to the implications for the organ at the other end of the bone-vascular axis.

Fahr disease

Idiopathic Basal Ganglia Calcification, also known as Fahr disease, is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement. Through the use of CT scans, calcifications are seen primarily in the basal ganglia and in other areas such as the cerebral cortex

Brain calcifications induce neurological dysfunction that can be reversed by a bone drug

Perivascular calcifications within the brain form in response to a variety of insults. While considered by many to be benign, these calcium phosphate deposits or "brain stones" can become large and are associated with neurological symptoms that range from seizures to parkinsonian symptoms. Here we hypothesize that the high concentrations of calcium in these deposits produce reversible, toxic effects on neurons that can be overcome with "bone" drugs that chelate solid phase calcium phosphates. We present preliminary findings that suggest a direct association between progressive neurological symptoms and brain calcification and the symptomatic improvement of seizures, headaches, and parkinsonian symptoms in patients treated with the bisphosphonate drug disodium etidronate, normally used to treat bone diseases. Future, longitudinal epidemiological studies and randomized trials will be needed to determine the true relationship between brain stones and neurological disorders as well as the utility of bisphosphonates in their prevention and treatment.

Possible therapies for brain calcification

Etidronic Acid

Etidronic acid (Didronel ®) is a bisphosphonate used to strengthen bone, treat osteoporosis, and treat Paget's disease of bone.
Bisphosphonates primarily reduce osteoclastic activity, which prevents bone resorption, and thus moves the bone resorption/formation equilibrium toward the formation side and hence makes bone stronger on the long run. Etidronate, unlike other bisphosphonates, also prevents bone calcification. For this reason, other bisphosphonates, like alendronate, are preferred when fighting osteoporosis. To prevent bone resorption without affecting too much bone calcification, etidronate must be administered only for a short time once in a while, for example for two weeks every 3 months. When given on a continuous basis, say every day, etidronate will altogether prevent bone calcification. This effect may be useful and etidronate is in fact used this way to fight heterotopic ossification. But in the long run, if used on a continuous basis, it will  cause osteomalacia.

Alendronic acid

Alendronic acid  — sold as Fosamax by Merck — is a bisphosphonate drug used for osteoporosis, osteogenesis imperfecta, and several other bone diseases. It is marketed alone as well as in combination with vitamin D (2,800 IU and 5,600 IU, under the name Fosamax+D). Merck's U.S. patent on alendronate expired in 2008 and the drug is now available as a generic. This is the most widely prescribed bisphosphonate medicine in the United States .

Vitamin K2

Vitamin K is a group of structurally similar, fat-soluble vitamins the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation that the body needs for controlling binding of calcium in bones and other tissues. The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise. Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. Low levels of vitamin K also weaken bones and promote calcification of arteries and other soft tissues.

Vitamin K2 is an approved drug therapy in Japan for dysfunctional calcium homeostasis where calcium is lost from your bones (osteoporosis)  and added to the lining of your arteries.

The mechanism involves something called osteocalcin, but is not fully understood.

Osteocalcin originates from osteoblastic synthesis and is deposited into bone or released into circulation, where it correlates with measures of bone formation. The presence of 3 vitamin K-dependent γ carboxyglutamic acid residues is critical for osteocalcin’s structure, which appears to regulate the maturation of bone mineral. In humans, the percentage of the circulating osteocalcin that is not γ-carboxylated (percent ucOC) is used as a biomarker of vitamin K status.

Osteocalcin also plays a yet to be understood role in the glucose metabolism and insulin sensitivity.  Indeed a clinical trial in humans has confirmed this effect exists.

Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial

To summarize, we have demonstrated for the first time that vitamin K2 supplementation for 4 weeks increased insulin sensitivity in healthy young men, which seems to be related to increased cOC rather than modulation of inflammation. Small sample size limits firm interpretation on β-cell function. Our results are consistent with previous studies that demonstrated improved glucose intolerance or relieved insulin resistance by treatment with vitamin K1  or vitamin K2 , respectively.



So while the mechanism remains unclear, vitamin K2 does much more than is commonly thought.

It is thought that the amount of vitamin K2 in diet is too low to keep calcium where it should be and the suggested daily amount in diet is too low.

Vitamin K in the treatment and prevention of osteoporosis and arterial calcification


The role of vitamin K in the prevention and treatment of osteoporosis and arterial calcification is examined.


Vitamin K is essential for the activation of vitamin K-dependent proteins, which are involved not only in blood coagulation but in bone metabolism and the inhibition of arterial calcification. In humans, vitamin K is primarily a cofactor in the enzymatic reaction that converts glutamate residues into gamma-carboxyglutamate residues in vitamin K-dependent proteins. Numerous studies have demonstrated the importance of vitamin K in bone health. The results of recent studies have suggested that concurrent use of menaquinone and vitamin D may substantially reduce bone loss. Menaquinone was also found to have a synergistic effect when administered with hormone therapy. Several epidemiologic and intervention studies have found that vitamin K deficiency causes reductions in bone mineral density and increases the risk of fractures. Arterial calcification is an active, cell-controlled process that shares many similarities with bone metabolism. Concurrent arterial calcification and osteoporosis have been called the "calcification paradox" and occur frequently in postmenopausal women. The results of two dose-response studies have indicated that the amount of vitamin K needed for optimal gamma-carboxylation of osteocalcin is significantly higher than what is provided through diet alone and that current dosage recommendations should be increased to optimize bone mineralization. Few adverse effects have been reported from oral vitamin K.


Phytonadione and menaquinone may be effective for the prevention and treatment of osteoporosis and arterial calcification.

Vitamin K2 reduces coronary heart disease:-

Dietary Intake of Menaquinone (Vitamin K2) Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study

In conclusion, our findings suggest a protective effect of menaquinone intake against CHD, which could be mediated by inhibition of arterial calcification. Adequate intake of foods rich in menaquinones, such as curds and (low-fat) cheese, may contribute to CHD prevention.

Reduce AGC Activity

Another option would be to reduce activity of AGC (mitochondrial aspartate/glutamate carrier) in the brain.  This is the realm of  mouse experiments.

In most neurodegenerative diseases there is too little AGC activity.   AGC is necessary for neuronal functions and is involved in myelinogenesis, so we again have to think about multiple sclerosis (MS).  MS is characterized by the loss of the ability to regenerate the myelin layer, so called remyelination. Autism is characterized by unusual myelination. 

Sulfatide is a major component in the nervous system and is found in high levels in the myelin sheath in both the peripheral nervous system and the central nervous system. Myelin is typically composed of about 70 -75% lipids, and sulfatide comprises 4-7% of this 70-75%.[2] When lacking sulfatide, myelin sheath is still produced around the axons; however, when lacking sulfatide the lateral loops and part of the nodes of Ranvier are disorganized, so the myelin sheath does not function properly.[5] Thus, lacking sulfatide can lead to muscle weakness, tremors, and ataxia

Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been suggested to  regulate the sulfatide metabolism.  That would suggest that low levels of vitamin K (from diet and produced by bacteria in the intestines) might reduce sulfatide levels and hence impair myelination.
So this would appear to suggest an overlap in the effect of vitamin K and AGC activity. 

We also discover that AGC is regulated by CREB in response to pathological inflammation.  Inflammation is a recurring theme in autism.

It turns out that CREB regulates numerous genes/proteins that are dysfunctional in autism, including:-
·        Somatostatin, also known as growth hormone–inhibiting hormone (GHIH)
·        Brain-derived neurotrophic factor BDNF
·        VGF nerve growth factor.  VGF expression is induced by NGF, CREB and BDNF and regulated by neurotrophin-3.
·        genes involved in the mammalian circadian clock(PER1, PER2).

CREB (cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences calledcAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.

Genes whose transcription is regulated by CREB include: c-fos, BDNF, tyrosine hydroxylase, numerous neuropeptides (such  assomatostatin,  enkephalin, VGF, corticotropin-releasing hormone),[2] and genes involved in the mammalian circadian clock(PER1, PER2).

CREB is closely related in structure and function to CREM (cAMP response element modulator) and ATF-1 (activating transcription factor-1) proteins. CREB proteins are expressed in many animals, including humans.

CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain and has been shown to be integral in the formation of spatial memory.[5] CREB downregulation is implicated in the pathology of Alzheimer's disease and increasing the expression of CREB is being considered as a possible therapeutic target for Alzheimer’s disease.[6] CREB also has a role in photoentrainment in mammals.

Somatostatin, also known as growth hormone–inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.

For our reader in Gdansk and parents of kids who do not sleep :-

Involvement in Circadian Rhythms

Entrainment of the mammalian circadian clock is established via light induction of PER. Light excites melanopsin-containing photosensitive retinal ganglion cellswhich signal to the suprachiasmatic nucleus (SCN) via the Retinohypothalamic tract (RHT). Excitation of the RHT signals the release of glutamate which is received by NMDA receptors on SCN, resulting in a calcium influx into the SCN. Calcium induces the activity of Ca2+/calmodulin-dependent protein kinases, resulting in the activation of PKA, PKC, and CK2.  These kinases then phosphorylate CREB in a circadian manner that further regulates downstream gene expression. The phosphorylated CREB recognizes the cAMP Response Element and serves as a transcription factor for Per1 and Per2, two genes that regulate the mammalian circadian clock. This induction of PER protein can entrain the circadian clock to light/dark cycles inhibits its own transcription via a transcription-translation feedback loop which can advance or delay the circadian clock. However, the responsiveness of PER1 and PER2 protein induction is only significant during the subjective night.

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1.

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

The mitochondrial aspartate/glutamate carrier isoform 1 gene expression is regulated by CREB in neuronal cells

The aspartate/glutamate carrier isoform 1 is an essential mitochondrial transporter that exchanges intramitochondrial aspartate and cytosolic glutamate across the inner mitochondrial membrane. It is expressed in brain, heart and muscle and is involved in important biological processes, including myelination. However, the signals that regulate the expression of this transporter are still largely unknown. In this study we first identify a CREB binding site within the aspartate/glutamate carrier gene promoter that acts as a strong enhancer element in neuronal SH-SY5Y cells. This element is regulated by active, phosphorylated CREB protein and by signal pathways that modify the activity of CREB itself and, most noticeably, by intracellular Ca2+ levels. Specifically, aspartate/glutamate carrier gene expression is induced via CREB by forskolin while it is inhibited by the PKA inhibitor, H89. Furthermore, the CREB-induced activation of gene expression is increased by thapsigargin, which enhances cytosolic Ca2+, while it is inhibited by BAPTA-AM that reduces cytosolic Ca2+ or by STO-609, which inhibits CaMK-IV phosphorylation. We further show that CREB-dependent regulation of aspartate/glutamate carrier gene expression occurs in neuronal cells in response to pathological (inflammation) and physiological (differentiation) conditions. Since this carrier is necessary for neuronal functions and is involved in myelinogenesis, our results highlight that targeting of CREB activity and Ca2+ might be therapeutically exploited to increase aspartate/glutamate carrier gene expression in neurodegenerative diseases.

Vitamin K2 and Myelin

Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, dihydrophylloquinone for 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 in the brain. The efficiency of dietary dihydrophylloquinone conversion to menaquinone-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to those in the hippocampus. There were significant positive correlations between sulfatides and menaquinone-4 in the hippocampus (phylloquinone-supplemented diet -12mo and 24mo; dihydrophylloquinone -supplemented diet - 12mo) and cortex (phylloquinone-supplemented diet -12mo and 24 mo). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dihydrophylloquinone to convert to brain menaquinone-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure, and behavior functions.
Low sulfatide content in brain myelin has been recently linked with the disruption of myelin integrity [14,21], whereas the disruption of myelin integrity was implicated as an essential contributor to cognitive deficit [6, 7, 43, 44]. Although our findings of dietary-associated decreases in myelin sulfatides suggest a potential disruption in myelin integrity in evaluated brain regions, it is currently unknown whether such disruption would be sufficient to modify motor and cognitive functions controlled by these brain regions.

In summary, this is the first study to demonstrate the effect of dietary vitamin K on sulfatides and MK-4 in the purified brain myelin. It remains to be determined whether long-term and/or higher dietary dK consumption would be sufficient to affect brain-region-specific changes in the: (a) number and/or metabolic activity of oligodendrocytes; (b) rate of myelin formation and loss, (c) activity of genes responsible for the synthesis of myelin constituents. Furthermore, the behavioral consequences of altered sulfatide concentrations through manipulation of dietary vitamin K remain to be assessed.

Vitamin K Biological properties relevant for an effect in MS – Vitamin K is a group of fat-soluble vitamins, needed for posttranslational modification of proteins involved in blood coagulation and bone metabolism. It includes two natural groups of vitamer chemicals: K1 (phylloquinone) and K2 (menaquinone). In addition to its effects of coagulation and bone metabolism, it has been demonstrated that oligodendrocyte precursors and immature neurons are protected from oxidative injury by vitamin K2 (61). Vitamin K has no known function in the immune system in humans. Trials in animal models – One study has been performed in the EAE-model (62). The authors reported that the severity of EAE was significantly ameliorated by the prophylactic administration of vitamin K2, although it was not effective when given after the onset. The authors reported that the vitamer seemed to work by inhibition of inflammatory cellular infiltration. Human trials – No human trials have been performed on the effect of vitamin K on MS disease activity or prevention.

Vitamin K as an antioxidant

Novel Role of Vitamin K in Preventing Oxidative Injury to Developing Oligodendrocytes and Neurons

Oxidative stress is believed to be the cause of cell death in multiple disorders of the brain, including perinatal hypoxia/ischemia. Glutamate, cystine deprivation, homocysteic acid, and the glutathione synthesis inhibitor buthionine sulfoximine all cause oxidative injury to immature neurons and oligodendrocytes by depleting intracellular glutathione. Although vitamin K is not a classical antioxidant, we report here the novel finding that vitamin K1 and K2 (menaquinone-4) potently inhibit glutathione depletion-mediated oxidative cell death in primary cultures of oligodendrocyte precursors and immature fetal cortical neurons with EC50 values of 30 nM and 2 nM, respectively. The mechanism by which vitamin K blocks oxidative injury is independent of its only known biological function as a cofactor for γ-glutamylcarboxylase, an enzyme responsible for posttranslational modification of specific proteins. Neither oligodendrocytes nor neurons possess significant vitamin K-dependent carboxylase or epoxidase activity. Furthermore, the vitamin K antagonists warfarin and dicoumarol and the direct carboxylase inhibitor 2-chloro-vitamin K1 have no effect on the protective function of vitamin K against oxidative injury. Vitamin K does not prevent the depletion of intracellular glutathione caused by cystine deprivation but completely blocks free radical accumulation and cell death. The protective and potent efficacy of this naturally occurring vitamin, with no established clinical side effects, suggests a potential therapeutic application in preventing oxidative damage to undifferentiated oligodendrocytes in perinatal hypoxic/ischemic brain injury.

In summary, we demonstrate for the first time that oxidative cell death induced by GSH depletion in primary OL precursors and in primary cortical neurons can be prevented by nanomolar concentrations of vitamin K1 and MK-4. The cytoprotective effect of K vitamins in this model is independent of their known biological role in carboxylation. They do not prevent the loss of intracellular GSH caused by cystine depletion but markedly inhibit ROS accumulation and, thus, cell death. These results suggest a new approach to developing potential preventative and therapeutic strategies for neurological diseases in which GSH depletion-induced oxidative stress plays a role.

L-Carnitine and Calcium Chelation

I think we have established the link between excess calcium and some types of mitochondrial dysfunction.

Regular readers will know that one important element in autism mitochondrial therapies, like Dr Kelley’s and others, is the supplement L-carnitine, which in responders seems to show effect very quickly.

Is it a coincidence that one of the properties of this supplement is as a chelator of calcium?

L-carnitine is a calcium chelator: a reason for its useful and toxic effects in biological systems

Chelation normally refers to removing harmful metals from the body.  In the case of calcium we just want to put it back in the bones, not remove it from the body.

The study earlier in this post appear to show that the brain calcium deposits do not grow over time, for some reason calcium got deposited very early in life and just stays there.  The deposits do not grow but do continue to do damage.  So considering them like brain stones might be helpful.   Therapies do exist for such brain stones, as we saw using drugs developed for osteoporosis.


Excess calcium maybe one of those few simple concepts in autism that you do not need a PhD to fully understand.  It may also be at the root cause of further complex dysfunctions where that PhD really would be useful.

I think some of those CREB-associated dysfunctions and indeed some mitochondrial problems might just disappear if any existing excess calcium was removed.

If you can go to the doctor to measure calcification in your heart, why not do it for your brain?  Coronary Calcium Scans are common and take about 10 minutes.

 If there is no brain calcification, great. 

If it brain calcification exists, then treat it, just like the doctor would treat Grandma’s osteoporosis.

Measure bone density; all women over 65 are recommended to have a DXA scan.  So the technology is already here.

Vitamin K2 is seen as very safe, but you might need to eat a lot of Natto if you have calcification, probably better used for prevention.

Why do the Harvard researchers who have noted low bone density in autism not make a few further connections and understand the implications and treatment options?
There were also interesting issues that arose regarding multiple sclerosis (MS), but that is not really an issue for this blog.

Vitamin K2 looks like yet another good thing for people with type 1 or type 2 diabetes.

I have to add vitamin K2 to my growing list of possible dementia therapies, before I forget. It affects myelin sulfatides, which are one cause cognitive decline in the elderly.

Final Words

This did become rather a lengthy post.

Vitamin K2 is likely highly beneficial for many people, but just how much you need to decalcify a brain is unknown.  I suspect far more than in your average supplement.
Perhaps the dosage in the Japanese K2 drug would have an impact.  The Western RDA is 0.075 mg a day;  in Japan they used 45mg in trials, a dose 600 times larger.

Cheap generic bisphosphonate drugs might be better and then K2 for maintenance therapy?

Some serious scientific investigation looks warranted, given the therapies are sitting on the shelf.   Don’t hold your breath.


  1. A lengthy post but an awesome post nonetheless. I will definitely be looking into Vitamin K more closely as I was previously unaware of calcification issues in those with autism.

    Unfortunately, I also have a lot to share with respect to your long post so you will have to read about as much of what I have to say as what you had to say (-:

    First off, I have read so many papers with respect to AGC my head might explode someday. Why you might ask? Nothing to do with Vitamin K, but rather an intervention I employed that I believe has had a huge effect on my son in terms of reducing SIB, aggression, and improving all around mood and focus and that intervention is L-Aspartic Acid. The idea for it is a very long story I won't get into but the reasoning for its use was based on some very old opioid receptor research (30 years or so) by a researcher from Turkey and here is one of the papers (not paywalled as many others are):

    If you want to read more about the researcher's reasoning for his treatment you can read the gajillion of his papers he self-cited below.

    As I said how I came across this is a very long story starting with a totally separate idea I had with regards to reducing glutamate levels in the brain (and general research thereof) and it led to everything else.

    Opioid dysregulation in classic autism has been beaten to death for well over 30 years now and also happens to be the prime reasoning behind the GFCF diet (opioid like peptides getting into the brain via a leaky gut and leaky blood brain barrier). Now, I don't believe the reasoning behind the GFCF hypothesis is solid at this time (reasonable people can agree to disagree), but I do believe that the evidence is clear for opioid dysregulation with respect to autism, especially with regards to more severe cases. Normalizing the opioid system won't cure autism, but treating it will help improve many of the core symptoms. Furthermore, a common therapy originally designed for opioid addiction called Low Dose Naltrexone (LDN) is being used by many doctors for other diseases including obesity, depression, and of course autism now. The research on opioid blockers and autism goes back quite some time, but mainstream therapeutic use seems somewhat recent from everything I have read on the subject. So this L-Aspartic Acid is effectively an alternative method of achieving similar results to strong opioid blockers (which have side-effects). While testing supplemental L-Aspartic acid myself, I did notice a significant reduction in hedonic desires (its a strange feeling), which is similar to what happens with people on Naltrexone.

  2. Now, if you want I can discuss my opioid hypotheses to fill up your entire front page, but as best I can tell L-Aspartic Acid does wonders (Google it and you get quack websites from quack doctors talking about Aspartate poisoning and neural excitotoxicity via the ingestion of Aspartame which IMHO is total nonsense) for possibly any number or even all of the following reasons:

    (1) Normalizing the opioid system via the mechanisms cited by the researcher in the many papers (I read all of them actually over the course of a week) he published on the subject.

    (2) Supplemental aspartate reduces ammonia levels in the body and brain. Ammonia seems to be quite high in autistic subjects for the studies I have read on the subject.

    (3) My original idea for aspartate was that glutamate and aspartate (L-Glutamic Acid and L-Aspartic acid actually) both compete with each other for the same transporter (the excitatory amino acid transporter or EAAT) for access into the brain. More aspartate may competitively block more free glutamate into the brain. This is not my strongest hypothesis since Aspartate, Glutamate, GABA, and Glutamine are all cycled between each other via various brain cells, but perhaps if there is a hiccup in those with autism from dysfunctional astrocytes (which convert glutamate to glutamine) then you might have an imbalance in the glutamate to GABA ratio. The research is very mixed in this area and what I think is the most likely at this time is that there is excess GABA in the brain, but also excess Glutamate as well (thereby creating an imbalance). Maybe supplemental Aspartate also helps normalize this system but this is just pure speculation on my part.

    (4) Maybe some sort of way of perturbing the malate aspartate shuttle if aspartate levels in the blood are low for some reason (maybe a metabolic hiccup from some dysregulated gene). Redox problems have been shown in autism via plenty of studies concerning oxidative stress and autism, so maybe supplemental L-Aspartic Acid helps in this way.

    The way I prepare it is by creating monosodium aspartate via mixing about equal amounts (by weight) of L-Aspartic Acid and baking soda in warm water. Mix it around for a while until it all dissolves, then you have a salty solution you can use as a salt substitute in food or as part of a base for soup.

    Now all this being said, probably every single DAN doctor in the world will say DO NOT USE MSG, DO NOT USE ASPARTAME, DO NOT USE, etc. etc. when the actual scientific evidence is pretty clear that concerns over total nonsense since most of Asia would all have dementia at age 40 by now if MSG, glutamic acid and aspartic acid were as bad as some people make it out to be. They are basic amino acids our body needs and the blood brain barrier is stubborn about letting too much of it in (most glutamate in the brain comes from glutamine which gets through the BBB in abundant amounts via a different transporter).

    Since, I don't want to steal your thunder I won't comment any more on this other than to say that was a great post that has given me a lot of new ideas just now with respect to not just Vitamin K but other things I have been working on for quite some time now. Oh yeah, and I would have posted this stuff a while ago on your blog but I wanted to wait a while to see if the intervention was a fluke or not. I employ a lot of other interventions so a sample size of 1 is not definitive, but personally I will say I believe this particular intervention has been a big win for my son.

    1. Thanks Tyler, I will take a good look at your intervention.

  3. Hi Peter, I thought I should make a few comments on your post, which I find highly informative, particularly at this period of time that my son seems to respond to Verapamil, a calcium channel blocker, and to Baclofen which affects the n-methyl d-aspartate glutamate receptors.
    First I have to go back to an "old relative", as you mention, my grandfather. My grandfather was a very respectable, well educated person, who also had severe kyphosis. Nobody was allowed to talk about it in case we hurt him. There was even a rumour spread that during his puberty he fell off a horse and crippled himself.
    When I became mature enough, I asked my uncle again and he told me that this was a fiction and his father actually suffered from some kind of calcium/vitamin D malabsorption due to malnutrition and living in a basement, having left home at a very young age in order to study. None of his six children seemed to have been affected.
    Now, as I was investigating possible reasons for my son's low LDL cholesterol, I found an article on pubmed relevant to DHCR7 expression and its important role for both cholesterol and vitamin D synthesis. This came as a surprise and I automatically connected my son's condition with his greatgrandfather's since they both seemed to have low expression of the same gene.
    To raise the expression of DHCR7, you had advised me on statins which I haven't trialled yet.
    Also I'd like to report a "tetany like" incident my son had two years ago. He experienced some kind of seizure activity consisting of involuntary muscle contractions together with a so called "risus sardonicus". I was terrified because I thought he had started having seizures. We checked it with encephalography and magnetic imaging but no seizure activity was found. Then we attributed the incident to his medication (zoloft, Zyprexa) and orthostatic tension.
    When I visited my new doctor we revised this incident and finally told me to forget about it. However, I can't forget that "tetany like" incidents happen due to calcium malabsorption.
    Furthermore my son has been on an osteogenesis operation in both legs and I have personal experience in bones density in autism. During the first month we had disappointing results, especially in his right leg. He also suffered from sleep disorder and it was at that time I started melatonin. Immediately after, his leg responded and when we started using Nac we had additional excellent results in bones density.
    I don't know if Nac and melatonin are as good as osteoporosis/vitamin D or K2 supplements but they seem to have worked wonders to my son's osteogenesis.
    I am sorry for being so chatty, but this blog is the only place I can testify my son's course of regressive autism.

    1. Hi Petra, thanks for all the information. Maybe it is worth giving vitamin K2 a trial? There is a very high strength K2 from the US. It is very much higher dose than the various pills you can find on Amazon. It is called "Thorne Vitamin K2 Liquid" it claims to have 1mg of K2 per drop; most pills have 0.1mg and 0.5mg in "high strength" versions. It is not cheap, but based on how much K2 you get, it is better value than the tablets.

  4. Hi Peter,
    This is a very interesting post to me. Myself, my son, and probably the rest of my family have some issues with calcium and especially oral vitamin D. Based on trying it, vitamin k is probably marginally helpful for us. My mother who has had issues with arthritis since her 40s was at one point given Fosamax and it made her problems much worse in that it seemed to calcify more tissues - not just increase bone density. This may be an atypical response and may be connected in with the negative response to oral vitamin D.

    1. Hi Seth, what kind of dosage of K2 did you use?

      The dosage in clinical trials is very high. They used 30mg a day in this trial showing the effect on insulin sensitivity.

      The Japanese use 45mg a day.

      I just ordered the liquid K2 that is 1 mg per drop.

    2. I was using Jarrow my-7 which is just 90 mcg which admittedly is a tiny dose. Regarding big doses I wonder if excessive clotting becomes a nontrivial risk. Probably not given what the Japanese are using.

    3. There is probably a dose between 90 mcg and 45mg where it is entirely safe, unless you are taking a drug like warfarin at the same time. I am sure the Japanese have considered this risk. They are treating adults, albeit small ones.

      There are a lot of people using K2 at high doses for all kinds of conditions, if you read the comments on Amazon and elsewhere.

    4. I agree my fears regarding clotting appear to be way overblown. As you have highlighted the Japanese researchers have really studied it with truly massive doses and evidently found no cause for concern. See: Thanks for the great post.

    5. The vitamin K2 you are referencing from Japan is MK-4 (menaquinone-4), a short chain form of vitamin K2 that has a very short life. They use MK-4 in three doses/day and this is not a lot since it has this short life.
      Vitamin K1 has about the same short life in the body and from food like leafy greens, it is absorbed in fairly small amounts - like in single digit to maybe 10-15%. So citing high K1 is nice but does not represent the amount truly absorbed by us.
      Vitamin K2 of long chain forms (MK-7 - MK-10ish) lasts a lot longer in the body and is almost all absorbed.
      So MK-4: short life, must multiple dose in higher amounts
      MK-7: long life, so 90 mcg is NOT a low dose, but more can truly be more, with no known ill effects except those on warfarin (not a good drug - makes soft tissue calcify)
      K1: short lived and not particularly available in food, but supplements are better absorbed
      If you take a K supplement, take it with a fat.
      There is incredible potential for a everyone with a better vitamin K status. Including more than just autism, brain health. Like heart health, diabetes risk, bone health, nervous system functioning.
      If you supplement, take the MK-7.
      If you want to get more long chain K2 in diet:
      eat liver, organ meats, offal, fermented foods
      Translation: yogurt, cheese, kefir, sauerkraut, natto, bivalves, liver, olives, etc.

  5. I am sure you are aware chelation is a popular treatment among parents who are convinced vaccines caused their child's autism.Many of these parents report significant improvements in their children,after these treatments.This causes said parents,and some less educated doctors,to assume that the autism was caused by "metals" from their child's vaccines.The subjects covered in this post were all new to me,but it does help explain to me why chelation might work in some cases of autism.You aren't chelating "metals" from vaccines,you are chelating calcium deposits out of the brain.That makes perfect sense.How are the vitamin D levels in these children?

    Here again you prove what I have suspected,that there would be a lot more older people with moderate to severe autism,had more parents kept their children out of institutions like my mother did me.These people would be very valuable to research.

    I have had many of the symptoms of demyelination.I had them for many years,starting in my early teens.I suspect,in my case,it was due to undiagnosed megaloblastic/pernicious anemia.Except for my neuropathy,which may or may not be related,the symptoms of demyelination went away after a couple of years on B-12 shots.My anemia is very severe.I only need to miss one day of my B-12 shots for symptoms to come back.

    Todd,it isn't just opioid peptides,it's also folate receptor autoantibodies,that are activated/regulated by consuming dairy.

    1. Chelators are potent antioxidants, so just that would help most people with autism. If excess calcium is present chelators certainly should have an impact. Another case of right for the wrong reason. The question is are potent chelators or drugs that affect calcium homeostasis the best therapy. This will be looked at in the next post.

  6. Peter, thank you for this post.

    My daughter has a problem with excessive plaque formation inspite of excellent oral hygiene. We have to clean extensively every few months, and it takes the dentist between two to three sittings to get it all. I have suspected calcium absorption and even tried K2 although at just 15mg per day. I stopped because her fibrinogen levels run high, even without the k2. She also seems to have persistent problems with her Vitamin D levels, currently she is testing low, below 30, but is not reacting well to supplementation. I suspect she also needs vitamin A as she has pilaris keratosis and vision issues. She has been a good responder to Verapamil, and I would like to trial a high dose of Vitamin K, but am unsure how to proceed.

    1. Many drugs affect calcium homeostasis. Vitamin A, antiepileptics, PPIs like Nexium are not good for your bones some drugs like statins are good for bones. k2 seems to do wonders for some people's teeth, but the same dose does nothing for other people. So each case will be a little different.

  7. Hi Peter, I am seriously thinking about trialling K2 Thorne supplement. How many drops would you start with?
    K2 helps with blood clotting and melatonin is considered to be a blood thinner. Do you think if taken together they would interact?

    1. Warfarin is the drug they say is unwise to combine with K2 and indeed they say not to combine melatonin with warfarin. Melatonin is present naturally and indeed if you take verapamil you may need to add back some extra melatonin, since apparently verapamil depletes melatonin.

      It might be prudent to lower your 10mg as suggested by your doctor to 3mg before trialing K2.

      I was thinking of starting with 5 drops, the full benefit in osteoprosis would require 45 drops.

  8. Peter, I was wondering if there is any research in autism and blood coagulation.
    We know that autism is susceptible to heart diseases. There is also research in healthy people under acute mental stress or exceeding coping skills who have been found with greater stress activity of the coagulation activation.
    I think this would be interesting to know.

    1. Petra there is one autism gene that is indeed connected to blood coagulation

      I think this is something very rare.

    2. MTHFR mutations are very common in autism.I have a few.MTHFR mutations often lead to problems with blood clotting.

  9. I just noticed one of the pictures of this blog post was that of Natto (high in Vitamin K). Natto is also very high in spermidine which can help with circadian disorders (my opinion only as based on a particular study in shifting the circadian cycle via exogenous spermidine supplementation in mice). Good luck getting an autistic child with taste sensitivities to eat Natto. Other good sources of spermidine are wheat germ and green peas, which are also unfortunately not very palatable to picky eaters either.

    1. You can buy Natto powder and if your kid can swallow pills you could put it in gelatin capsules. Many K2 supplements are derived from Natto.

      I think the K2 liquid 1 drop = 1 mg may be the simplest.

    2. Natto powder? Never heard of that (never really looked into it either). My understanding is that Natto is a fermented product with live cultures. Well I guess you learn something new every day (-:

  10. What do you make of an eight year old with autism who:

    1) can't tolerate much calcium but has to have a little bit with his magnesium, or else he gets numb and tingling fingers;

    2) has a history of hypotonia and lethargy and improves from calcium, but gets too hyper and insomniac;

    3) with CBD oil, can tolerate much more calcium, and can suddenly sing a whole song the very same day as testing the calcium increase to see how high it can go;

    4) speech sound production improves from additional calcium;

    5) had a growth spurt after bumping up his calcium, after starting CBD oil and noticing he could tolerate more calcium.

    1. Hi Jennifer, CBD (cannabidiol)has numerous pharmalogical effects. The one that seems to be helping your son appears to be increasing the level of calcium inside the cell.

      "CBD increases intracellular calcium concentrations via mitochondrial uptake and release and/or activation of type-L voltage-gated calcium channels"

      Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

      In other people with autism this same effect might actually make them worse.

      Calcium ions are key signaling messengers and any dysfunction would have many follow on effects on neurotransmitters etc. It might well explain the growth spurt.

      The thing to note is that it is not a case to too much or little calcium, it is where the calcium is. If giving oral calcium has improved the extracellular/intracellular calcium balance and gives just beneficial effects you are indeed fortunate.

      CBD oil has many other effects that may also help such as being a PPAR-γ receptor agonist. CBD oil has FDA approval for use in Dravet Syndrome, a rare kind of autism with epilepsy.

    2. I've come across another study on CBD showing the opposite effects on those calcium channels, that is the influx of calcium into the cell via L-type channels was REDUCED in the presence of CBD. This is most likely related to different amounts used in the studies (this U-curve effects is common with things affecting membrane permeability to ions). We probably have no way of knowing right now how the amounts used in those in vitro studies translate in real life, but in any case it seems that CBD might be affecting some calcium pathways/channels, and so affects how the other ones function.

    3. It is also possible (?) that the particular oil you are using has some THC present in it, which usually has the opposite physiological effects to CBD.

    4. It's Bluebird Botanicals hemp CBD oil, so it only contains a trace amount of THC. It's legal to sell in all fifty states.

  11. Hello Pierre. Thank you for the post.I am really a newbie and I've always struggled with my daughter's sleep. She is autistic (4years,36lbs). The blood test shows high levels of calcium (we are following a GFCF diet). Should I stop supplementing calcium and use vitamin K2? kind regards.

    1. If she has high levels of calcium already, you should talk to her doctor, since there may be an underlying issue like primary hyperparathyroidism.

      Giving her even more calcium seems unwise.

      Giving her vitamin K2 looks very safe, but it would not be top of my list of things to try. I would look at antioxidants (NAC in particular) and bumetanide first.

    2. Thank you very much for your insights, I've run a hair test which shows out of chart levels of lead. And with theses information I am sure that lead poisoning didn't explain all.
      Please can I have your email to share with you my daughter's medical tests, in my country I didn't find a doctor who believe on autism biomedical.
      thank you again

    3. I am not a doctor.

      You will either have to do the investigation yourself, using some trial and error, which is what most readers of this blog are doing, or go and see a biomedical doctor.

      You can achieve a lot yourself and many biomedical doctors appear not to be so knowledgeable.

      There are a lot of expensive tests that are of little value. I put hair testing in that category.

  12. Thank you for your insights, you've already gave me priceless tracks to explore.
    kind regards

  13. Dear Peter, "This did become rather a lengthy post." Haven't laughed so hard for so long. Yes, it was a lengthy post, but interesting. I also think you pasted the same text twice, somewhere?

    It would take me about a week to respond to this blogpost the way I would like.

    You are touching upon many of the same topics I study (very amateurly).

    Not sure how you can write about calcium dysregulation without mentioning magnesium. Think of calcium as the antithesis of magnesium.

    I can't get into every aspect of your blogpost right now, but I would like to say that osteoprotegerin levels may be high in children with autism because a female sex hormone estrogen is required (plus vitamin k2) for the body to utilize osteoprotegerin. From my understanding, osteoprotegerin is actually good to have as it keeps calcium out of soft tissues. K2 is beneficial for some for the very reason that it helps make osteoprotegerin (in combination with estrogen). The issue is of course being that males with autism have an extreme male brains and extreme male hormone balances, and likely a lack of that female hormone estrogen. So to sum it up, k2+estrogen=osteoprotegerin. Again, this is where magnesium might again come in, as magnesium is known to regulate hormones.

    This study illustrates how osteoprotegerin is actually good and protects against supplemental vitamin D.

    Also, elevated cytokines are highly associated with magnesium deficiency.

    Yes I fully agree that many of the benefits seen from Andy Cutler's ALA chelation therapy are likely due to the removal of excess, dysregulated calcium, and iron for that matter. Also note that a prerequisite of that program is Mg supplementation and I wonder if some parents are seeing a benefit just from that, yet misattributing the benefits to ALA. I will try to write more later.

  14. My bad, many individuals with autism have high cortisol, which often means low testosterone. (I think I was mixing up elevated testosterone in utero as a risk factor for autism with testosterone levels later in life.) Still, many people with autism still have affected estrogen expression, which might affect the use of k2. Keeping in mind that aromatase (required for the biosynthesis of estrogen) is required for the use of osteoprotegerin, "We found that the children with autism didn't have sufficient estrogen receptor beta expression to mediate the protective benefits of estrogen."
    Comparing the brains of 13 children with and 13 children without autism spectrum disorder, the researchers found a 35 percent decrease in estrogen receptor beta expression as well as a 38 percent reduction in the amount of aromatase, the enzyme that converts testosterone to estrogen.

  15. I may have some relevant experience; I'm a 61 year old Aspie with severe osteoporosis (L1 "T" score of -3.3). While investigating my numerous other health problems, I stumbled onto research regarding the PTEN gene and realized I almost certainly have PHTS (I'm on my second thyroid tumor now). While researching PTEN disorders, I realized that the pediatric version of PTEN disorders, BRRS, was consistent with my symptoms and experiences in my youth. While researching BRRS, it mentioned low carnitine levels in boys with BRRS. So I thought maybe I should try some carnitine, but did not know how much to take. So I tried researching carnitine dosage, and stumbled onto research on Chinese men with osteoporosis, which stated that 4 grams a day of carnitine had cured (not just stopped the loss of bone, but cured!) osteoporosis. So I thought, what the heck, it is just a supplement available without prescription at most pharmacies, what could it hurt? After I started taking L-Carnitine at the 4 gram dose, I immediately got relief from muscle spasms I have suffered with all of my life. My hands also stopped trembling. Then over time, my chronically broken ribs and thumbs healed. I was eventually (less than 6 months after starting on L-Carnitine) able to go back to work, and do household repairs and yard work again. My experience may only be valid for people with PTEN gene defects, or only for Chinese men, but I think it merits more research...

    1. Very interesting and thanks for sharing.

    2. Anonymous--- I would be very interested in what type of L-Carnitine you took. I am taking L-Carnitine Fumarate and have not done well with acetyl-l-carnitine.

  16. Thank you for interesting information. I have twin daughters 8, yrs old with epilepsy and a lot of problems. Recently we discovered problems in calcium metabolism - osteoporosis, bed teethes, low ionic calcium, low PTH, but normal total Ca, Mg, vit D3. They are getting calcium, magnesium, vitamin D3 but I am not sure it really works well. One has tetany, other had facial muscle twitches. Muscle twitches improved, but not tetany. Just few days ago I stumbled upon K2, and now I am looking to see if this could help them. I visited several pages, asked questions, but all I could get is "consult your physicians". There is NO HELP from any physician I consulted because their condition is so complicated and it seems that I already know more then they know. They are on gluten free diet, lactose intolerant, rotation diet because of food sensitivities. In this story I am completely alone... Rotation diet caused problems probably because they are allowed to eat a lot of oxalate reach food, removal of the milk was not possible despite lactose intolerance and obvious problems with constipation, etc. So there is lot of problems overlapping each other and I know the gut is the place I should start first. And there is no help from probiotics. It brings me back to K2 which I think they are missing. First is, could I do harm with K2? Calcium supplementation I think caused improper bone growth on their feet's forming some kind of bunions.

    1. This comment has been removed by the author.

    2. K2 is used in extremely high doses in Japan for osteoporosis. It does not seem to have problems unless given together with Warfarin an oral anticoagulant drug. Warfarin has many interactions.

      If someone has a dysfunction in calcium metabolism, K2 would seem a sensible thing to try. I am currently giving it a trial and there have been no side effects at all.

      Hypocalcemia is the primary cause of tetany and there are various causes including:-

      (1) The usual cause of tetany is lack of calcium. An excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms

      (2) Underfunction of the parathyroid gland can lead to tetany.

      (3) Low levels of carbon dioxide cause tetany by altering the albumin binding of calcium such that the ionized (physiologically influencing) fraction of calcium is reduced; one common reason for low carbon dioxide levels is hyperventilation

      (4) Low levels of magnesium can lead to tetany.

      (5) Clostridium tetani toxin, via inhibition of glycine-mediated and GABA-ergic neurotransmission, may lead to tetany.

      (6)An excess of potassium in grass hay or pasture can trigger winter tetany, or grass tetany, in ruminants.

      It looks like your daughters are being treated for Hypoparathyroidism (seizures plus low PTH, treated with calcium plus vitamin D3). This is a well known medical condition and this type of epilepsy should be treatable. I would go and find a specialist who might be able to optimize their drug therapy.

      Here is a paper on the treatment of adults:-

  17. Peter, I am looking at your blog post more carefully today and I realized that you cited this study: "Dystrophy with Calcification within Brains of Autistic and Control Subjects" found here : Am I reading this study incorrectly - or - are they saying that both the subjects with autism AND the controls had brain calcification? Just wondering. If they are saying that both groups showed the exact same levels of calcification, that seems a bit less meaningful for autism research. I could be misinterpreting though. Thanks.

    1. I included that very brief paper because it is very recent, but I agree that it actually says very little. They say that everyone has calcification, but the key issue is surely how much. I think we would only expect a minority of people with autism to possibly be affected and this was a study of just 13 people with autism. So the study was a nice idea but the result does not tell us anything conclusive. We do know that calcification is a feature of disease, we know it would affect functioning and we know some people with autism have dysfunctions with bone density and indeed vitamin D metabolism. So we know strange things are going on with calcium in the bodies of some people with autism.


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