Supplement Alert! Carlson Labs Vitamin K2 MK-4 (Menatetrenone).

In 2003, I started supplementing with one a day of Ultra K2 Menatetrenone (MK-4) 15mg (plus 1.5g/day of Ca plus 400mg/day of Mg plus ~1,000iu/day of Vitamin D3) to reverse osteoporosis in my lumbar spine (bone density by DEXA went from -2SD to 0SD) in 3 years. I then used a maintenance dose of 15mg per week (~2,200ug per day). Everything was fine.

At some point, I switched to one a day of Vitacost Ultra Vitamin K with Advanced K2 Complex. Everything was fine.

Around 2012, I switched to one a day of Carlson Labs, Vitamin K2, 5 mg, in order to use-up my remaining iHerb rewards from the use of my discount code NIG935. I'd lost ~$300 of rewards through non-use. Everything was fine - for a while.

In ~2014, my right hip joint, which had previously caused me pain due to iliotibial band impingement on a bony/calcified outgrowth (cured when I began K2 supplementation), began to cause me pain again. As sleeping on my right side worsened the pain, I began to sleep on my left side. My GP felt my right hip joint and declared that there was some "wear & tear" in it and to use topical analgesics. This helped a bit.

In ~2015, my left shoulder joint, which had previously caused me pain due to impingement on a bony/calcified outgrowth (cured when I began K2 supplementation), began to cause me pain again. I assumed that it was "wear & tear", so I put up with it and applied topical analgesics. This helped a bit.

I recently looked-up rotator cuff pain and was perplexed to see that it was usually caused by impingement on a bony/calcified outgrowth. This of course is quite impossible, if taking 5mg/day of K2!

I took a look at the product reviews on iHerb.com, and noticed comments about joint pains from some reviewers, so I ordered a pot of Ultra K2 Menatetrenone (MK-4) 15mg.

Within a week of switching from Carlson Labs to Vitamin Research Products, my joint pains had virtually* all gone.

Therefore, there's something wrong with Carlson Labs, Vitamin K2, 5 mg. DO NOT USE!

*As the rotator cuff is damaged, there will always be some shoulder pain. As a herniated disk in my lumbar spine (before my osteoporosis was reversed) damaged nerves to/from my right leg, I walk lop-sidedly which means that there will always be some hip & knee joint pain.

Calcium shift: An interesting hypothesis.

More serendipity! Billy the k left a comment that piqued my curiosity.

From http://www.health-heart.org/acceuil.htm The atheroma 'junk' in the media is cholesterol + calcium in older people.

From Aging and calcium as an environmental factor. (emphasis mine)
"The consequences of calcium deficiency might thus include not only osteoporosis, but also arteriosclerosis and hypertension due to the increase of calcium in the vascular wall, amyotrophic lateral sclerosis and senile dementia due to calcium deposition in the central nervous system, and a decrease in cellular function, because of blunting of the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency and others.

I highlighted amyotrophic lateral sclerosis in red, as many Facebook friends have been having buckets of water & ice cubes tipped over themselves to raise money for research into this horrible & ultimately fatal condition.

So, what prevents & reverses migration of calcium from hard tissues to soft tissues?
Clue: It carboxylates osteocalcin in bone matrix Gla proteins. Yes, it's Vitamin K2.

See also Calcium, parathyroids and aging. N.B. 50iu/kg bodyweight/day of Vitamin D3 significantly lowers parathyroid hormone.

A "discussion" with Dr. Garth Davis M.D.

I put "discussion" in quotes, for reasons which will become obvious.

The Pyramid of Disagreement. You should be using the top 3 levels at all times.

I've written this because Dr. Davis has blocked me from leaving comments on his Facebook page, and I really need to reply to his last reply to me.

See https://www.facebook.com/drgarth/posts/834305339923709
I was acutely aware as an omnivore, of "walking into the lion's den", by posting a dissenting comment on a vegan's thread, but it was necessary as I had evidence of harm of vegan diets. The evidence on Denise Minger's teeth is supported by her own blog. The evidence on Jay Dinshah's fatal heart attack at the age of 66 is supported by a YouTube video by Dr Michael Greger, the vegan M.D. Dr Greger's video showed evidence of other harms caused by vegan diets that were lacking in vegan DHA & Vitamin B12.

EDIT: Dr. Davis has deleted all of my comments. However, he hasn't deleted his replies to them.

It's impossible to prove a hypothesis, even with n=1,000,000, as the 1,000,001th subject could be the "Black Swan" that disproves it. On the other hand, it only takes 1 "Black Swan" to disprove it. Therefore, n=1 evidence of harm is sufficient to disprove a hypothesis that something is harmless. See Falsifiability.

I provided n=2 evidence of harm.

Dr Davis' last comment to me:-
" Nigel Kinbrum really? You are giving me a n of 2. There is no data that vegans teeth fall out. If she was vitamin K deficient then she was eating a crappy diet lacking greens. It so stupid it's just silly. I also laugh at the idea that authority is some how bad. I have written a book with thousands of references. I give lectures on the topic and have treated thousands of patients yet Denise knows more than me. Silly."

My reply:-
1. As stated above, an n of 2 is double the n needed to disprove your hypothesis that there is no evidence of harm for vegan diets. I'd already pointed that out to you in a previous comment that you've since deleted.

2. I said that Denise's teeth were disintegrating. I didn't say that they fell out. That's a strawman fallacy.

3. Greens contain phylloquinone (Vitamin K1), not menatetrenone (Vitamin K2). Only Vitamin K2 carboxylates osteocalcin in MGP's. The only vegan source of Vitamin K2 is Nattō, a.k.a. pungent beans in a snot sauce.

4. See 3. Denise Minger was not eating a "crappy diet". That's an extremely insulting & uninformed comment for a medical professional to make about someone.

5. I never claimed that authority is bad. When you say "I am an expert in "X", therefore I am never wrong about "X".", that's an "Appeal to authority" fallacy. Jeez!

6. See 5. I never claimed that Denise Minger knows more than you. That's another strawman fallacy.


So, there you have it. Comments will only be approved if they meet my Moderation Policy. As long as I am blocked from commenting on Dr. Davis' Facebook page, Dr. Davis is blocked from commenting on my blog.

Why do some people have trouble doing things in moderation?

This is related to my previous post.

From http://www.kindredcommunity.com/2013/01/xtreme-eating-awards-2013-extremism-running-amok-at-americas-restaurant-chains/

Some people take low-carbing to an extreme, 'cos if reducing carbohydrate intake has benefits, reducing it to zero must be better. Oy!


We're told that eating 5 portions of fruit and vegetables a day is good for us. One patient who was admitted to St George's with malnutrition, had been eating more than 50 portions of fruit and vegetables a day, 'cos if 5 portions of fruit and vegetables a day is good for us, 50 portions of fruit and vegetables a day must be better. Oy!


People who are taking the anti-clotting medication Warfarin need to maintain an accurate balance between their warfarin dose and their Vitamin K intake to keep their INR between 2 and 3, as warfarin antagonizes vitamin K₁ recycling, depleting active vitamin K₁.
"Between 2003 and 2004, the UK Committee on Safety of Medicines received several reports of increased INR and risk of haemorrhage in people taking warfarin and cranberry juice. Data establishing a causal relationship is still lacking, and a 2006 review found no cases of this interaction reported to the FDA; nevertheless, several authors have recommended that both doctors and patients be made aware of its possibility. The mechanism behind the interaction is still unclear." Here's a clue...

From Possible interaction between warfarin and cranberry juice (emphasis, mine):-
"After a chest infection (treated with cefalexin), a man in his 70s had a poor appetite for two weeks and ate next to nothing, taking only cranberry juice as well as his regular drugs (digoxin, phenytoin, and Warfarin). Six weeks after starting cranberry juice he had been admitted to hospital with an INR (international normalised ratio) > 50. Before, his control of INR had been stable. He died of a gastrointestinal and pericardial haemorrhage. He had not taken any over the counter preparations or herbal medicines, and he had been taking his drugs correctly." Cranberry juice contains no Vitamin K. Oy!

"The Committee on Safety of Medicines has received seven other reports through the yellow card reporting scheme about a possible interaction between warfarin and cranberry juice leading to changes in INR or bleeding. In four cases, the increase in INR or bleeding after patients had drunk cranberry juice was less dramatic. In two cases, INR was generally unstable, and in another case INR decreased. Limited information is available about whether patients complied with their treatment in these cases.

Cranberry juice (Vaccinium macrocarpon) is popular and is also used to prevent cystitis. Interaction with warfarin is biologically plausible, because cranberry juice contains antioxidants, including flavonoids, which are known to inhibit cytochrome P450 enzymes, and warfarin is predominantly metabolised by P450 CYP2C9. The constituents of different brands of cranberry juice may vary, and this might affect their potential for interacting with drugs. Whether the constituents of cranberry juice inhibit CYP2C9 and therefore the metabolism of warfarin or interact in another way needs further investigation. Until then, patients taking warfarin would be prudent to limit their intake of this drink." Oy!

So, one man's inadvertent (his doctor should have warned him about eating next to nothing while taking warfarin) dietary extremism resulted in his own death and the restricted intake of cranberry juice for everybody else taking warfarin. Oy. :-(


P.S. It's about time an alternative to warfarin was found. It's difficult to maintain an accurate balance between warfarin dose and Vitamin K intake.

Siri-Tarino et al, Forests & Trees and "Eureka!" moments.

Here's Fig. 2 from Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease:-

Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to coronary heart disease and stroke.

The above "Forest" plot has a subtotal RR of 1.07 (95% CI 0.96 1.19). The overall conclusion is that there's no association between saturated fat intake and the RR for CHD. Hmmm.

I looked at the data in Table 3. Of the 16 studies contributing to the CHD results, only 3 of them specify high sat fat intakes over a wide range. The results from these 3 studies are as follows:-

Pietinen et al: RR=0.93 (95% CI 0.6, 1.44).
Mann et al: RR=2.77 (95% CI 1.25, 6.13).
Boniface et al: Pooled RR = 1.37 (95% CI 1.17, 1.65).

The results from Pietinen et al are statistically-insignificant (95% CI values are way above & below 1) with an overall slight protective effect. The results from Mann et al have a RR >> 1 with both 95% CI's >1 and the results from Boniface et al have a RR >1 with both 95% CI's >1.

Other studies either have sat fat intakes varying from very low to low, or specify mean/median sat fat intakes without values for highest & lowest tertiles/quartiles/quintiles etc. Other studies have results that are statistically-insignificant.

However, there are some studies that show a slight protective effect of small amounts of sat fats. How come?

Thanks to George Henderson, I had a "Eureka!" moment. He posted a link to Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.

Here's Fig. 1 from that study.

HRs and 95% CI's of CVD risk according to quintiles of energy-adjusted SF from different sources (n = 5209).

The Meat SF plot has a net positive slope (bad news, but the range of intake is very small), the Butter & Plant SF plots are random, but the Dairy SF plot has a net negative slope (good news). Dairy saturated fats in amounts of up to 10g/day are protective against CHD. As the Dairy sat fat intake is too small to have a significant effect on lipids, what's the mechanism? I think that it's Vitamin K2. See Chowdhury et al, More forests & more trees and more "Eureka!" moments with cheese.

When you average out the results from all studies, the result is null. This is data dilution statistics.

EDIT: See also Study: Saturated Fat as Bad as Sugar!

Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

The good:

Here's a plot of mean (±SEM) plasma glucose concentrations during an oral-glucose-tolerance test (OGTT) when preceded by either a high-fat (▪) or a high-carbohydrate (□) evening meal and during an oral-fat-tolerance test (OFTT) when also preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

An OGTT (100g of glucose dissolved in water) causes a large disturbance in blood glucose level for up to 2 hours. Ditto for insulin (see Fig. 2).

An OFTT (40g of fat as cream) doesn't cause a significant disturbance in blood glucose level. Ditto for blood insulin (see Fig. 2).

The bad:

Here's a plot of mean (±SEM) plasma triacylglycerol concentrations during an oral-fat-tolerance test (OFTT) when preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

An OFTT (40g of fat as cream) causes a significant rise in blood triacylglycerol (a.k.a. TAG a.k.a. triglycerides a.k.a. TG's) level for up to 4 hours. Note that the effect of a preceding high-carbohydrate meal on fasting TG's is only +0.1mmol/L. Is high postprandial TG's a problem? Definitely, maybe. From Cholesterol And Coronary Heart Disease , "Cholesterol-depleted particles oxidise faster than large, cholesterol-rich ones." Chylomicrons, chylomicron remnants & VLDL-C are triglyceride-rich, cholesterol-poor, as that's the composition of the fat in the diet.

The ugly:

Here's evidence that excessive postprandial TG's significantly raise the relative risk (RR) for CHD:- See Fig. 1 in Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women.

Here's more evidence that postprandial saturated fatty TG's raise the RR for CHD:- See Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling.

See also Postprandial triglyceride-rich lipoprotein changes in elderly and young subjects.,
Effect of a single high-fat meal on endothelial function in healthy subjects.,
Postprandial lipemia: emerging evidence for atherogenicity of remnant lipoproteins.,
Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men.,
Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects.,
Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes.,
Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress.,
High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis.,
Impact of postprandial hypertriglyceridemia on vascular responses in patients with coronary artery disease: effects of ACE inhibitors and fibrates.,
[Influence of postprandial hypertriglyceridemia on the endothelial function in elderly patients with coronary heart disease].,
Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size.,
Association between fasting and postprandial triglyceride levels and carotid intima-media thickness in type 2 diabetes patients.,
[Correlation of lipemia level after fat loading with manifestation of atherosclerosis in coronary arteries].,
Postprandial hypertriglyceridemia and carotid intima-media thickness in north Indian type 2 diabetic subjects.,
Association between postprandial remnant-like particle triglyceride (RLP-TG) levels and carotid intima-media thickness (IMT) in Japanese patients with type 2 diabetes: assessment by meal tolerance tests (MTT).,
Postprandial lipemia and remnant lipoproteins., 
Elevated levels of platelet microparticles in carotid atherosclerosis and during the postprandial state.,
Postprandial metabolic and hormonal responses of obese dyslipidemic subjects with metabolic syndrome to test meals, rich in carbohydrate, fat or protein.,
Atherosclerosis, diabetes and lipoproteins., 
Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol.,
Post-prandial hypertriglyceridemia in patients with type 2 diabetes mellitus with and without macrovascular disease.,
A hypertriglyceridemic state increases high sensitivity C-reactive protein of Japanese men with normal glucose tolerance.,
CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis., 
[Trends of evaluation of hypertriglyceridemia -from fasting to postprandial hypertriglyceridemia-].,
The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells.

See also What Is the Significance of Postprandial Triglycerides Compared With Fasting Triglycerides? , Uncovering a Hidden Source of Cardiovascular Disease Risk and Postprandial Lipoproteins: The storm after the quiet!

A counter-argument is that the subjects in the above studies were eating carbohydrate, and that postprandial TG's aren't atherogenic if you're not eating much carbohydrate. Definitely, maybe. In the absence of carbohydrate, there is still glucose in the blood, thanks to the liver. Also, some carbohydrates don't spike blood glucose (or fructose) level. It's pure speculation that the subjects in the above studies had high blood glucose at the same time as high postprandial TG's. As Insulin Resistance/Metabolic Syndrome and/or a high-sugar diet raise fasting TG's, and there was no significant association between fasting TG's and the risk factor for CHD, this suggests that the subjects had no significant metabolic derangement and were not eating excessive amounts of sugar.

According to Very Low-Carbohydrate and Low-Fat Diets Affect Fasting Lipids and Postprandial Lipemia Differently in Overweight Men, there's a ~50% reduction in postprandial TG's after adaptation to a very-low-carb, very-high-fat diet. However, mean energy intake was only 1,850kcals/day. The subjects were in a 500kcal/day energy deficit and the %E from fat was only 60%.

Also, some people's LDL levels go extremely high on a very-low-carb, very-high-fat diet. See Lipidaholics Anonymous Case 291 Can losing weight worsen lipids? A very high LDL level results in a high LDL particle count, even if the particles are large (Type A). A high LDL particle count is a strong risk factor for CHD. See also Fig. 1 in Some Metabolic Changes Induced by Low Carbohydrate Diets.

It's possible to get Coronary Artery Calcium (CAC) scans, to measure the amount of calcified plaque in coronary arteries. While a high CAC value means lots of plaque, a zero CAC value doesn't necessarily mean zero plaque, as young people and people with a high Vitamin K2 intake don't have significant calcification. See Stenosis Can Still Exist in Absence of Coronary Calcium.

Update 26th July 2014: See Page 10 of  HIGH CARBOHYDRATE DIETS: MALIGNED AND MISUNDERSTOOD - Nathan Pritikin. Read the text, starting with:-
"Could such a cream meal precipitate an angina attack because the oxygen-carrying capacity of the blood is lowered?"
The answer appears to be "Yes."

Rigid diets & taking loadsa supplements to compensate for them.

I do not believe you want to be doing that!

This post was inspired by a recently-published study by Alan Aragon & Brad Schoenfeld, as bodybuilders are a group of people who often eat a rigid diet (some eat skinless chicken breasts, broccoli & brown rice for several meals each day).

See Nutrient timing revisited: is there a post-exercise anabolic window?
"Collectively, these data indicate an increased potential for dietary flexibility while maintaining the pursuit of optimal timing."

This post is also aimed at people who eat severely restricted diets in the (often mistaken) belief that something's making them ill.

People with type 1 diabetes who struggle to keep their blood glucose within reasonable limits (3 to 8mmol/L, or 24 to 144mg/dL) benefit from restricting their intake of high-GL carbohydrates, so this post is not aimed at them. See The problem with Diabetes.

People with type 2 diabetes who severely restrict their intake of carbohydrates must be in caloric deficit, otherwise the physiological insulin resistance caused by high serum NEFAs will mess up just about everything in their body if they are in caloric balance or caloric excess. I've read (so it could be false) that a certain non-skinny blogger who I'm in conflict with (who has type 2 diabetes and who eats a VLC diet) has heart problems and is taking medication(s) for high blood pressure. Hmmm.

People who suffer from gastrointestinal problems after eating gluten-containing foods, or mucus after eating casein-containing foods may have impaired gut integrity. See Gluten - more than just a pain in the guts?

Supplements that I consider of positive value are:-

Fish oils: If the diet is low in oily fish (tinned tuna is not an oily fish), there may be insufficient EPA & DHA (especially in men, children & post-menopausal women). Women of reproductive age can get away with taking flaxseed oil.

Magnesium: If the diet is low in veg/high in dairy, there may be too much Calcium relative to Magnesium.

Vitamin D3: If the lifestyle results in sun-avoidance, insufficiency in Vitamin D is highly likely.

Vitamin K2: If the diet is low in animal fats and/or fermented foods, insufficiency in Vitamin K2 is highly likely.

Supplements that I consider of negative value are:-

Vitamin A: If there's an insufficiency in Vitamin D, supplementing with Vitamin A/β-carotene may exacerbate it. As Vitamin D + Calcium may reduce cancer risk, supplementing with Vitamin A absent Vitamin D3 may increase cancer risk.

Vitamin E: If there's an insufficiency in γ-tocopherol, supplementing with α-tocopherol may exacerbate it. As γ-tocopherol may reduce CHD mortality risk, supplementing with α-tocopherol absent γ-tocopherol may increase CHD mortality risk. Most Vitamin E supplements contain α-tocopherol only. Some Vitamin E supplements contain mixed tocopherols and these are O.K.

\ curves and U curves: Vitamins D3 and K2 again.

Here are some curves relating to Vitamin D. Ref: http://www.ncbi.nlm.nih.gov/pubmed/23601272

Hazard Ratios (HRs) vs serum Vitamin D level

The solid lines are the 95% confidence intervals (CI) & mean for all-cause mortality. 95% CI's are the values within which 95% of the subjects tested fall. 2.5% fall below the lower CI and 2.5% fall above the upper CI. The dashed lines are the 95% CIs & mean for coronary heart disease (CHD) mortality. Most of the curves follow a \ curve, indicating that more Vitamin D is better, up to 66ng/mL (150nmol/L, the level that I'm at). The interesting curve is the upper dashed line, which follows a U curve.

The U curve indicates that a Vitamin D level of greater than 30ng/mL (75nmol/L) increases the Hazard Ratio (HR) for CHD in the top 2.5% of subjects only, relative to 30ng/mL, even though the mean HRs for CHD & all-cause mortality (the more important parameter) are decreasing, up to 66ng/mL. What's occurring?

See Vitamin K. The increase in HR for CHD mortality above 30ng/mL in the top 2.5% of subjects only is almost certainly due to calcification within artery walls, due to under-carboxylation of osteocalcin in bone Matrix Gla Proteins, caused by insufficient Vitamin K2 rather than excessive Vitamin D. This is why I supplement with Vitamin K2. See also Vitamin D toxicity redefined: vitamin K and the molecular mechanism.

Cancer, part 2.

In cancer, I discussed omega-3 and methylglyoxal.

Methylglyoxal

This time, I'm just going to do a Research Review, by publishing a list of PubMed searches with the following Filters activated: Abstract available, published in the last 10 years, Humans.

Cancer AND "Dichloroacetic Acid".

Cancer AND "Magnesium".

Cancer AND "Methylglyoxal".

Cancer AND "Omega-3".

Cancer AND "Vitamin D3".

Cancer AND "Vitamin K2".

I added searches for Magnesium and Vitamin K2, as I supplement with those and want to see if they have a positive or negative effect on Cancer. I added Dichloroacetic Acid (DCA), as I've read about it.