What causes heart disease part VIII

The healing process

Most people, when they think about atherosclerotic plaques, think of them as starting very small – as fatty streaks and suchlike. Then they inevitably get bigger and bigger over many years. However, this is not correct:

‘Atherosclerosis was originally considered to be an ongoing process that was inevitably associated with age. However, plaques are highly dynamic, and are able to progress, stabilize or regress depending on their surrounding milieu. A great deal of research attention has been focused on understanding the involvement of high-density lipoprotein in atherosclerotic plaque regression. However, atherosclerotic plaque regression encompasses a variety of processes that can be grouped into three main areas: removal of lipids and necrotic material; restoration of endothelial function and repair of denuded areas; and cessation of vascular smooth muscle cell proliferation and phenotype reversal.’ 1

In short, progression is not inevitable. Plaques can shrink down in size, the smooth muscle proliferation (often considered and irreversible components of plaques) reversed, and endothelial function restored. In truth, you will most likely not end up with a perfectly healed plaque with no signs it was ever there. You will be left with a bit of a ‘scar’ or some sort. However, the important point is that we are not looking at a one-way street. The body can heal plaques. (Probably not once calcified, but that is another issue).

This leads me onto the third part of the process of CVD. As I have been discussing in this series, the process of CVD has four basic components:

  • Endothelial damage
  • Clot formation/dysfunctional clot formation
  • Clot repair/dysfunctional clot repair
  • The final, fatal, blood clot

Up to now I have mainly talked about endothelial damage, and clot formation, which are plaque ‘growth’ factors. However, repair is also very important. Anything that can interfere with the repair process is going to make plaques grow, rather than regress.

The key players in repair are: monocytes, macrophages and Endothelial Progenitor Cells (EPCs). As mentioned several times before, once the endothelium is damaged, and a clot formed, EPCs are attracted to the area to form a new layer of endothelium. So, clearly EPCS are critical players. Just to quote one paper:

‘BACKGROUND: Cardiovascular risk factors contribute to atherogenesis by inducing endothelial-cell injury and dysfunction. We hypothesized that endothelial progenitor cells derived from bone marrow have a role in ongoing endothelial repair and that impaired mobilization or depletion of these cells contributes to endothelial dysfunction and cardiovascular disease progression.

CONCLUSIONS: In healthy men, levels of endothelial progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease.’2 Which means that with fewer EPCS, plaques grow faster.

The critical part that EPCs have to play is also seen in patients who have angioplasty, or stents. Immediately following the procedure, the bone marrow starts making more EPCs.

‘In conclusion, endothelial injury from angioplasty can lead to time-dependent mobilization or homing of EPCs; mature EPC subpopulations are actively mobilized, and may contribute more to endothelial reparation; and the mobilization amplitude of the main EPC subpopulations is significantly influenced by the degree of endothelial injury and certain clinical factors.’3

It follows that, if you have fewer EPCs the risk of CVD will be much higher. This is clearly seen in Systemic Lupus Erythematosus (mentioned a few times before). The paper quoted from below looked at SLE, and the number of EPCs, and also haematopoietic stem Cells (HSCs) – which are the precursor to EPCs – found in the bone marrow:

‘SLE patients have lower levels of circulating HSC and EPC, even during clinical remission. Our data suggest that increased HSC apoptosis (cell death) is the underlying cause for this depletion. These observations indicate that progenitor cell mediated endogenous vascular repair is impaired in SLE, which may contribute to the accelerated development of atherosclerosis.’4

Other conditions, or factors, that reduce EPC numbers include:

  • Type II diabetes
  • Avastin
  • Rheumatoid arthritis
  • Smoking

To name but four.

Of course there tends to be a tight association between factors that damage the endothelial cells, and factors that reduce EPC number. This appears to be primarily modulated by nitric oxide levels. Anything that increases NO levels in endothelial cells and also helps to protect them from damage appears to increase EPC production in the bone marrow.

A non-exhaustive list of things can do this this are:

  • Exercise
  • L-arginine/L-citrulline
  • ACE-inhibitors (used for BP reduction)
  • Statins

Yes, the dreaded statins… Boooo! In truth, for many years I have accepted (albeit with great reluctance), that statins do have some benefits in CVD. Not enough, in my opinion, to overcome the damage that they can do. However, the benefit is there, it is real.

I knew it could be nothing to do with the impact of statins on lowering LDL, as LDL has nothing to do with CVD (well, almost nothing). So there had to be another effect. And that effect is, in my opinion, almost entirely to do with the ability of statins to increase nitric oxide (NO) production:

‘Endothelial nitric oxide (eNO) bioavailability is severely reduced after myocardial infarction (MI) and in heart failure. Statins enhance eNO availability by both increasing eNO production and reducing NO inactivation. We therefore studied the effect of statin treatment on eNO availability after MI and tested its role for endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular (LV) dysfunction, remodeling, and survival after MI….. These findings suggest that increased eNO availability is required for statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, LV dysfunction, interstitial fibrosis, and survival after MI. eNO bioavailability after MI likely represents an important therapeutic target in heart failure after MI and mediates beneficial effects of statin treatment after MI.5

Yes, when you decide to look through a different prism, you can find that things you thought were one thing, turn out to be another thing entirely. Professor Michael Oliver – a trenchant critic of the cholesterol hypothesis before statins came along – changed his mind, once he saw that statins lowered LDL and lowered CVD risk. Case proven – he said.

No, case not proven. Instead, if you look at EPCs and nitric oxide (NO) and take the view of CVD that it is all due to endothelial dysfunction, blood clotting and impaired repair, you can see exactly where statins may fit into the picture.

Next: The final event.

References:

1: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209544/

2: http://www.ncbi.nlm.nih.gov/pubmed/12584367?dopt=Abstract

3: http://www.spandidos-publications.com/etm/10/2/809

4: http://ard.bmj.com/content/early/2007/02/28/ard.2006.065631.abstract

5: http://www.ncbi.nlm.nih.gov/pubmed/15466656

194 thoughts on “What causes heart disease part VIII

    1. IAN FRAME

      Once again on BBC R4 Today Programme they are perpetuating the myth that statins are god for you (whilst at the same time conceding that “good” cholesterol is not necessarily good for you.

      Reply
  1. JanB

    Thank you, Dr. K. Just when you think it couldn’t get any better it does. Every instalment is enthralling.

    Reply
  2. martinedmundson

    A very big thank you for the ‘technical’ details contained in your articles. With the knowledge you gave me my Cardiologist, last week during an unusual ‘annual recall’ check, said that he liked patients that ‘took control for themselves’ with the support of their Doctor rather than rely totally on their Doctor to ‘do everything’. He was particularly amused by the tale of my negotiation to reduce the statin dose so “Victor Meldrew” was banished but allowed the good effects, as outlined in part VIII, to continue and having to put up with the ‘side effect’ of interfering with cholesterol. He acknowledged and agreed that some of the Official Advice for CVD was lagging behind scientific developments on the subject.

    Reply
  3. Geoff Broughton

    Hi Dr Malcolm
    After going through having a heart attack some 6 years ago I had stents fitted, given the usual plethora of pills including statins, quickly lost confidence in their effectiveness as my health appeared to continue on a downward slope. After taking on board some research courtesy of internet searching (which included your book ‘The Great cholesterol Con’) and much more including nutritional research (most substantial benefit from Gary Taubes’ ‘The Diet Delusion’ but not excluding William Banting’s efforts those many years ago, I decided to take my own course of action. I ditched all the pills, went on a LCHF eating regime and exercised a little more. My eczema practically totally cleared within 2 weeks (had been applying Betnovate for a number of years) and within a couple of months or so the quite distressing at times haemorrhoids also completely cleared – which leads me to your articles.
    I don’t think that they were intended for the likes of myself for there appears little benefit (I am not a doctor). My experiences as described above were very real. They only describe a succession of events although they obviously suggest that my health problems had their grounding in poor nutrition. I did indeed regularly have a large quantity of ‘fruit & fibre’ cereal for my breakfast prior to my heart attack, I also enjoyed sweets such as jelly babies, turkish delight and others. I loved bread in the form of sandwiches. Sat atop all of this was the family stress of trying desperately to help my youngest daughter rid herself of serious drug addition. Herein lie the causes, the combined effect of the stress, the (may I suggest) symptomatic eating patterns. The background chemistry, may I suggest, is also symptomatic of that internal, holistic, but mainly mental or even spiritual driving force for health and wellbeing that is in all of us and that we continually prefer to bypass because of some mistaken need or reasoning.
    I remain of fan of yours as the help that your original book offered me is undeniable and gave me the courage to delve much further, but not into the realms of chemistry.
    Many, many thanks, and best regards
    Geoff Broughton

    Reply
    1. Tony

      Geoff, my story, my experiences and my continued longevity shares a similar background and experience to yours; long live us argumentative, questioning, stubborn yet flexible in our views punters………who go round the houses, and then, all of a sudden, from our research a light bulb comes on…………..eureka! Our evidence of research could be said to be ‘anecdotal’ but we are the living proof of our search for our personal pathway to our own health… I raise my glass to my fellow conspirators…

      Reply
    2. Stergio

      Totally agree Geoff. We belong to a generation that has been fed statins and bad dietary advice regarding a fat free diet. I too have read Malcolm’s blog and others such as the Diet Doctor re LCHF diet. I too have come to the decision to stop the statins, walk for miles and reduce carbs. I have also decided to take Vit K2 supplements as I remember the surgeon e playing he ‘had to give an extra push’ to break through a calcified cardiac artery as he inserted my stent. I have lost weight, 12kg in two months, and feel fitter. I cannot say I have had the stress you have had regarding your family but I have had a lifetime’s work as a MH professional. So yes stress is a factor. Best wishes.

      Reply
  4. luboff33

    Are we going to find out, what actually causes the body to be in the state where all the changes to the blood vessels you have described, causes the ideal conditions for CVD to occur? That is, is there anything we can do to prevent it happening – diet? exercise? lifestyle? supplements? anything at all?

    Reply
      1. Jennifer

        Jolly good….I look forward to reading it with anticipation, and many thanks for all your work in this field.

      2. Craig

        Kevin –
        ‘These effects are at least partially mediated by lowered insulin-like growth factor-1 levels in the blood and stem cell microenvironment’

        Lowering protein intake lowers igf-1 levels, specifically foods high in methionine eg eggwhite, sesame and parmesan cheese. There are some who claim that igf-1 is the key to the benefits of intermittent fasting.

        We just have to hope now that the benefits of the nitrate in bacon outweigh the disadvantages of the protein – there is so much nitrate in celery juice that it can be used to cure bacon btw. And now it seems beetroot might also be good for that.

        I told you all that parseley is a superfood!

      3. goutboy

        Eat real food, get enough sleep, don’t worry, get vit d and exercise. Oh and roll the dice. If it’s a 6 it’s CVD, 5 cancer, 4 Dementia, 3 Bronchial stuff. 2 &1 too close to call, maybe hit by asteroid.
        Love the blog BTW.

      4. Bob Niland

        re: Eat real food,…

        Ah, but which real food? The choices there matter quite a lot. This is a choice we all need to make multiple times per day, every day.

        re: …get enough sleep, don’t worry, get vit d and exercise.

        Agreed. The sleep issue isn’t just a question of “enough”. Vit. D titer is important, and perhaps higher than you might guess.

        re: Oh and roll the dice.

        Other than “get new ancestors”, there’s probably less dice rolling than imagined. Dramatically reducing CVD risk is within reach. Start by entirely disregarding the advice of government agencies, national affliction associations and doctor’s unions.

      5. Dan

        I hope it arrives soon. Hate to die of a heart attack before you reveal your insights.

        Joking aside, this is starting to connect with Ignarro’s work on NO which he won the nobel prize.

      1. Gary Ogden

        Jill Mitchell: Agreed. Also, complete avoidance of industrial seed oils (meaning no restaurant fried foods), such as corn, soybean, sunflower, safflower, and canola. And avoidance of wheat, especially whole wheat, and sugar only on special occasions.

  5. Jennifer

    So my smoking, hypertensive, diabetic friend, who insists on continuing to take statins, (as opposed to my stance of banishing them entirely), may indeed have a point!
    Heck…I am confused now, but I will not be reintroducing statins, despite arguments to the contrary.
    Call me stubborn, but I suffered greatly, and eventually blamed stains. The fact that my health has improved considerably since eliminating them, is enough proof for me.

    Reply
    1. David Bailey

      Jennifer,

      Remember that the studies have always shown tiny gains for people on statins, but the Numbers Needed to Treat (NNT’s) are insanely small:

      http://www.thennt.com/nnt/mediterranean-diet-for-post-heart-attack-care/

      I think this is the thing to remember, If you had been given statins and told by the doctor that he would have to give statins to 83 people (one number on the NNT site) for 5 years, but that far more people would suffer crippling side effects, you would never have started!

      I am most certainly not restarting my statins!

      Reply
      1. BobM

        David, do you mean the NNT are large (and not small)? It was my impression that the larger the NNT is, the worse the drug is.

      2. Stephen T

        And that’s the lowest NNT I’ve seen, David. I think it’s a drug industry figure. Prof Noakes says 140 and figures go as high as 300. NNT means the number needed to treat for one person to benefit. The higher the figure, the less useful the drug or treatment. Roughly one person in, say, 100 – 150 benefits slightly, but how many are harmed? Everyone to some extent? Many seriously. I doubt anyone would take them who knew these figures.

      3. Jennifer

        David, I did try so hard to resist the GP’s insistence a number of years ago, but was accused of ‘looking up stuff on the internet ‘, which was apparently not good form. It took lots of courage to finally take the plunge and go it alone, and I am now stronger in mind, body and spirit these days, and far more able to call my own shots, so to speak, regarding my health management.
        “The lady doth protest too much, methinks” I hear the doc say! ‘And about time too! ‘. ….is my reply!

      4. mikecawdery

        94% saw no benefit and there is no harm. Conversely simvastatin (the HPS study) only 0.003% benefited and 99.7% saw no benefit p.a. with a harm rate of up to 20%

        Been very busy as patient reviewer for BMJ

    2. Stephen T

      Jennifer, Dr K, said a small benefit but not enough to outweigh the damage. He couldn’t be clearer on his opinion of statins. If your friend smokes when she has diabetes and hypertension, I would be rushing to seek her medical advice.

      Reply
  6. Gearoid OLaoi

    That’s good stuff Malcolm.. Mind you I was of this opinion already! On 10 Mar 2016 19:50, “Dr. Malcolm Kendrick” wrote:

    > Dr. Malcolm Kendrick posted: “The healing process Most people, when they > think about atherosclerotic plaques, think of them as starting very small – > as fatty streaks and suchlike. Then they inevitably get bigger and bigger > over many years. However, this is not correct: ‘Atherosc” >

    Reply
    1. David Bailey

      That was an interesting,article but I wonder about the advice about eating foods rich in nitrates, because I had always understood that these could form nitrosamines in the stomach, and that these are carcinogenic. Indeed I thought that was the rationale for not eating bacon too often – because it is cured with nitrates.

      Is it a case of the risk being outweighed by the benefit, or has the risk associated with the consumption of nitrates overplayed?

      Reply
      1. Bob Niland

        re: …nitrates, because I had always understood that these could form nitrosamines…

        That would be the nitrites (with 2 “i”s). This confusion is probably why the nitrates are now commonly hidden as celery juice or celery powder.

      2. Gary Ogden

        David Bailey: No doubt the risk of nitrates has been overplayed (I believe very little of what is printed in newspapers, other than the comics and the puzzles). And what have they replaced cured bacon with? “Uncured” bacon, prepared with celery powder, and this bacon apparently has more nitrates than cured bacon! Three cheers for nitrates.

      3. John U

        I once had an email back and forth discussion re nitrates and nitrites with a local science newspaper columnist. I provided references to 4 studies I gleened from pubmed showing no problem with these compounds. The columnist dropped the subject and moved on to other topics.
        I have never found a good research study on humans which implicated nitrites in any illnesses. No doubt that nitrosamines may be harmful, but, as with all toxins, the dose counts.

      4. David Bailey

        Bob Niland,

        If there is confusion, it is not mine! I remember one scare associated with nitrates getting into the water supply is/was that these might result in cancer. The point may be that nitrates can be reduced easily to nitrites, possible in the stomach.

      5. Martin Back

        When I was with Water Affairs in Namibia I learned there was always an outbreak of nitrate poisoning in rural babies when the rainy season started. This was because the cattle grazed the river bank vegetation in the dry season when there was no water flow, and when the rains started the rivers absorbed nitrates from the accumulated droppings and flushed them into the wells.

        “High nitrate levels in drinking water pose a health risk to infants because they may cause methemologlobinemia, a condition known as “blue baby syndrome.”

        High nitrate levels interrupt the normal body processes of some infants. Nitrate becomes toxic when it is reduced to nitrite, a process that can occur in the stomach as well as in the saliva. Infants are especially susceptible because their stomach juices are less acidic and therefore are conducive to the growth of nitrate-reducing bacteria. (Adults can consume large quantities of nitrates in drinking water or food with no known ill effects; their stomachs produce strong acids that do not promote the growth of bacteria that convert nitrate to nitrite.) Nitrite in the blood combines with hemoglobin to form methemoglobin, which reduces the capability of the blood to carry oxygen to all parts of the body. This results in the “blue” condition of the baby’s skin.”http://www.idph.state.il.us/envhealth/factsheets/NitrateFS.htm

      6. Mec Cham

        In response – the following has just been put up in Science Daily –
        Fertilizer applied to fields today will pollute water for decades
        Posted: 14 Mar 2016 06:14 PM PDT
        Dangerous nitrate levels in drinking water could persist for decades, increasing the risk for blue baby syndrome and other serious health concerns, according to a new study.
        https://www.sciencedaily.com/releases/2016/03/160314211406.htm

        Much of interest in today’s edition –

  7. Essop Hajat

    I am a great fan and came to know your work after falling victim to rhabdomyolysis caused by Simvastatin. A scrip happy GP prescribed them for me for “slightly high” cholesterol of 5.2, he was determined to lower my cholesterol and offered to change the brand of statin. I politely declined and the symptoms disappeared soon after stopping. I now recommend you as essential reading to anyone who will listen.

    I have read that CoQ10 levels are severely depleted in people who are on statins and indeed anyone who has CVD. How does this square with the apparent boosting of eNO with statins? i would rather use the natural products which are available to increase eNO production.

    Reply
    1. Mec Cham

      Quote : “I now recommend you as essential reading to anyone who will listen.” Yes. Same for me. Terrific input from Dr Kendrick, have been following him for a long time – tends to be my ‘bible’… Just wish his papers were beside ALL beds in hotel rooms

      Reply
  8. dearieme

    (i) If statins work, insofar as they do, by encouraging production of NO, that implies that it might be wise to develop a drug aimed at increasing NO as its target, rather than depending on a side-effect of the original purpose of statins. (ii) If statins help a little with CVD, why do they appear not to extend life? In other words, what are their malign effects that cancel out their beneficial effect?

    Reply
    1. Joe

      Statins have been shown to increase both the risk of becoming diabetic substantially, which shockingly increases the risk of heart disease. And most shocking (sarcasm again) big pharma doesn’t reflect that increased heart risk when assessing either CVD specific risk or overall mortality. There are many many other serious side effects. While increasing NO with a drug might be helpful, the most natural solution is to eliminate the inflammation that damages the endothelial layer by minimizing / eliminating infection, elevated insulin / cortisol and the unusual (evolution wise) constant emotional stresses from lack of sleep, traffic, lousy bosses, etc. Paleo / Primal diet and lifestyle (low carb preferred) is my belief as to one of the quickest paths to better health. Throw in some intermittent fasting and I bet your relative risk of dying goes way down IMHO.

      Reply
      1. BobM

        Joe, in my opinion, you’ve hit the nail on the head. I was diagnosed with idiopathic dilated cardiomyopathy, which I believe was caused primarily by stress but insulin resistance did not help and also may have caused/exacerbated it. (Of course, don’t look to a cardiologist to ask you what your insulin, blood sugar, or hemoglobin A1c levels are.) I’ve taken steps to reduce my stress level, and I started (for good) a low carb diet. I later added intermittent fasting to that. Now, after over two years of this, I’m much healthier than I was: IBS, tinnitus, skin tags, irritable/overactive bladder, chest congestion, all dramatically reduced or gone. Note also that I rarely eat wheat, which supposedly causes some of this. I’ve also been using resistant starch over the last couple of months to get my bowel flora back in order (though I’m going to quit this at the end of this month to see what happens). I’ve even started taking oral probiotics, which — amazingly — have helped my oral health a ton.

        For me, statins would be way down on my list of what to do to make myself healthy. (Now, if I could only get off the drugs — ACE inhibitor and beta blocker — for cardiomyopathy, but I haven’t done enough research about these to make any judgement.)

      2. 1truth1reality

        Hi Bob, Your post from yesterday a.m. reflects similarities in your circumstances to mine. Have you read? Do you feel we can gain from comparing notes further? Are you in the medical profession? (I am not)

      3. Gary Ogden

        BobM: I, too would like to wean from the ACE inhibitor I take, but, like you, don’t know enough to decide if there is more harm than good in them. On the principle that the body well knows how to heal itself, given proper conditions of lifestyle and in the absence of complicating genetic defects, I’m inclined to think I would be better off without it. At 67 I have no diseases or conditions, only very minor aches and pains, and sleep like a rock. I do a strenuous, muscle-building workout every third day. Dr. Kendrick tells us that ACE inhibitors increase levels of EPC.s, which is a good thing, but apparently these drugs can harm the kidneys by somehow interfering with the sodium/potassium balance (why my physician makes it a point to tell me how good my kidney function is, by the two blood tests she orders each year, one of which is creatinine). Dr. K has other fish to fry, but I wish someone with more knowledge that we would weigh in on the issue.

      4. Dr. Malcolm Kendrick Post author

        Gary. I cannot chase every comment down with a great deal more information. What I do know is that L-arginine/l-citrulline increases NO synthesis and stimulates EPC growth. I know that sunshine increases NO synthesis throughout the body. I am not suggesting everyone takes an ACE-inhibitor (far from it). I just used them as an example. I believe the benefits of ACE-inhibitors, unrelated to BP lowering, are due to positive impact on NO synthesis.

    2. Brian Wadsworth

      Reading the original studies used to gain approval for sale shows that they increase cancer rates so that longevity remains more or less the same. It is just that there are fewer heart attacks.

      Reply
    3. Mec Cham

      NO : AAKG – Alpha Arginine KetoGlutamate – freely available. I take it every day. Solgar sell and also Doctor’s Best. Both reliable brands – Brilliant series Dr Kendrick. Agog for the rest – and thanks for all your hard work –

      Reply
    4. Craig

      ‘In other words, what are their malign effects that cancel out their beneficial effect’

      I have a feeling that no-one will ever get funding to explore the mechanisms of the various evils of statins whether they are simply due to the diverse downstream effects of inhibiting hmgCoA reductase in which cholesterol lowering is collateral damage, or maybe via some other completely novel pathway(s).

      The effects which i suffered after only 3 months use were so vile and accompanied by such a pervasive mental fog that i would never again consciously elect to take them. Granted that they may have use in very specific medical emergencies, I find it very difficult to understand how such drugs could ever have been approved for general, seemingly casual use.

      Statins – the recreational drug for drug companies? Statin useage re-creates their bank balances.

      Reply
      1. Mr Chris

        Craig,
        You make an interesting remark here “a complete mental fog”
        When I decided to give up a minimal Crestor dose together with Ezetrol, it was the muscle pain that decided me. Now in fact I realise that I had a sort of mental fog, and grumpy old man syndrome, irritable with everyone and so on.
        18 months after stopping that gradually cleared away. Not an easy side effect to explain or describe, but I am convinced it was there.j

  9. Gay Corran

    More good stuff. I continue to be on the edge of my (diabetically controlled) seat. I would also love to find out who pays our vegan friend to give his dogmatic but scientifically unsupported views on this blog. Grateful and continued thanks, Dr K.

    Reply
  10. JDPatten

    Dr. Malcolm,
    “(Probably not once calcified, but that is another issue)”
    But… “they” are telling us all – more vehemently every day – that calcification is the consequence of atherosclerosis, therefore direct evidence of it. Yes? No exceptions??
    Calcification is the main reason I’ve been following you these weeks.
    You’ll have more, yeah?

    Reply
  11. Gary Ogden

    Thanks again, Dr. Kendrick, and thanks to Jerome Burne for the informative article. What I find fascinating is the healing process in atherosclerosis. I don’t recall seeing much, if anything, in the press about this over the years, but it makes sense that there would be an active healing process for endothelial damage as there appears to be for all other physical injuries.

    Reply
  12. JDPatten

    Dr Malcolm,
    Would you extend this list a bit?:
    Type II diabetes
    Avastin
    Rheumatoid arthritis
    Smoking
    I was wondering if it might include diseases of the endothelium: e.g. Typhus. (Rickettsia)

    And this list:
    Exercise
    L-arginine/L-citrulline
    ACE-inhibitors (used for BP reduction)
    Statins
    I was wondering if it might include ARBs as a nitric oxide booster.
    It seems that angiotensin would figure in the whole process somehow.

    Reply
  13. JDPatten

    Hypothesis:
    If one were on a powerful statin for a substantial period of time, experiencing the artificial endothelial progenitor boost (and the nasty side effects), and then quit… would s/he experience withdrawal?
    Lower than normal EPC levels?

    Reply
  14. mr Chris

    Dear Dr Kendrick,
    I recently have had a replacement hip and, even more recently broke two bones in my foot. The hospital prescribed paracetamol at 1 gm, each time which I took for about a15 days. Noticing that it seemed to increase my blood pressure, I did a search and came up with this as a possible reaction, “because of modification of endolethial function”. Can you explain this?
    thanks

    Reply
    1. Emma

      Paracetamol depletes glutathione (GSH), our extremely important intra-cellular antioxidant. My understanding is that this is how paracetamol damages and ultimately kills, and the treatment for overdose is NAC, a type of protein from which our cells make glutathione. (Why oh why isn’t there NAC in all paracetamol tablets / Calpol etc?) Anyway, high dose or continued paracetamol = lowered GSH = increased damage and inflammation.
      Talking of antioxidants, and reading Dr K’s list of examples of things which increase or decrease CVD risk, I am reminded of Gilbert’s Syndrome. Perhaps Dr K has already covered it / will cover it, but this is a fairly common condition, in which there is increased levels of bilirubin in the blood, the body doesn’t clear it away as efficiently as it does in those without GS. Sounds like a problem, doesn’t it? If your GP diagnoses you with it, they may attempt to reassure you, and say it’s not severe and nothing to worry about. But don’t expect them to tell you that unless severe, having GS is a MASSIVE health advantage! Your risk of ischemic heart disease is SO dramatically reduced that you would think cardiologists would be falling over themselves to find a way to give everyone GS. And why is GS so astonishingly protective? Presumably because bilirubin, this reddish bile pigment, is a potent antioxidant.

      Reply
      1. Anne

        Can you send me a link about the benefits of having high bilirubin please Emma ? My husband has Gilbert’s syndrome !
        Anne

      2. Anne

        PS hubby also has high homocysteine – I wonder does that cancel out the protection conferred by Gilbert’s syndrome ?

      3. Lindy

        This looks interesting re: bilirubin. -http://www.longecity.org/forum/topic/41651-bilirubin-the-overlooked-key-to-caloric-restriction-and-intermittent/

      4. Emma

        Hi Anne, I can’t seem to reply to your reply, so am replying to myself! Wikipedia briefly mentions that those with GS have a third of the risk of CVD as those without GS. A third!!!
        I wonder if some of those instances of ‘well my Great Uncle Bob lived until he was 95 and smoked 60 a day and drank 10 pints a night and ate nothing but macaroni pies’ might have had GS. Anyway, here are a couple of links:
        http://www.ncbi.nlm.nih.gov/pubmed/11849670
        http://circ.ahajournals.org/content/114/14/1476.full
        As for high homocysteine, makes sense to tackle it despite the protective effect conferred by GS. If current supplements aren’t normalising homocysteine make sure he is taking the right amounts and the right forms. Try Folate (active folic acid), Pyridoxal-5-Phosphate (active B6), and B12 as Methylcobalamin or Adenosylcobalamin rather than cyanocobalamin. Other useful additions are TMG, SAMe and NAC (the aforementioned antidote to paracetamol overdose). Incidentally, those with GS should avoid paracetamol, as it may be even more toxic to them than it is for those without GS. So there you go, another cardiovascular benefit of having GS…

      5. JanB

        Oh dear. I didn’t mean YOU, Dr. K. – you’re much too busy doing all this wonderful research and besides I was only half serious. Obviously a tongue in cheek doesn’t show in a posting. Sorry.

      6. Dr. Malcolm Kendrick Post author

        No problem. Maybe I take on too much. Today working for 13 hours, typing between patients. Someone tell Jeremy Hunt that he’s right. Doctors don’t work at weekends… ho, ho. [Hm I wonder what he is doing today].

      7. Emma

        Sorry everyone, mortified. After writing ‘Gilbert’s Syndrome’ I was just using GS as an abbreviation thereafter. TMG, SAMe and NAC are all amino acid (types of protein) nutritional supplements, that’s how they are often sold / referred to, which saves calling them Tri-methyl glycine, S-adenosylmethionine and N-acetlycysteine!

      8. JanB

        Please don’t feel mortified, Emma. It’s the problem with a site like this where medics/non-medics, scientists/non-scientists rub shoulders. I think I shall start a little notebook to jot down all the acronyms as they occur. That way I can enhance my education a little (a very little)

      9. Dr. Malcolm Kendrick Post author

        Indeed, no need to feel mortified. Acronyms are always a problem. Every day in the NHS, someone lobs a new acronym at me, and I have to ask what it is. Latest one BBA. BBA, let me think. It stands for bed bureau administration. Just what the world needs I feel.

  15. Randall

    Dr. Kendrick, because endothelial cells have no GLUT4 (glucose transporter), is this not the very, very beginning of the damage to endothelial cells? After eating a meal the damage starts little by little because they cannot defend themselves. Sugar can increase reactive oxygen species (ROS), which can damage and kill cells. Last night I met with W. Gifford-Jones, M.D. (Fellow of The Royal College of Surgeons) who retired at age 87, said I should publish this. By the way he is another Dr. that does not like statins, believes in Vitamin C and L-Lysine for CVD.

    Reply
  16. michael goroncy

    Increasing Nitric Oxide:

    “A non-exhaustive list of things can do this are: from Dr K.
    Exercise
    L-arginine/L-citrulline
    ACE-inhibitors (used for BP reduction)
    Statins “
    Not sure what Planet you people live on…but her on ‘Planet Goroncy’
    Exercise ….not optimately achievable for many people due to other ailments. Although anything is better than nothing.
    ACE-inhibitors (used for BP reduction) ….unfortuanately , a large % of people have a side effect of dry cough.
    Statins….absolutely for ‘Secondary prevention’ only.
    L-arginine/L-citrulline ….aha! Effective supplement. Although! I would elaborate and add 2 others that work synergytically.
    Cardiac Combo = daily dosage:
    L Arginine x 6 grams
    L Citrulline x 1 gram
    Alapha Lipioc Acid x 50-100 mg
    Ascorbic acid x 500mg (this is for ratio purpose) take as much as you can tolerate throughout the day.
    Optional:
    Vitamin E x 200 iu
    Folate x 800 mc

    Reply
    1. Dr. Malcolm Kendrick Post author

      Michael. Thanks for that list. At present, in this series, I have not (yet) tried to bring together a list of things to take, or not take. I hope that what I am doing it giving people a clear rationale for why some things will probably help – through their impact on endothelial damage/clot formation/plaque repair. People can then decide on which things to use – and which things are particularly damaging

      Reply
    2. Dr. Göran Sjöberg

      My own ‘anti-drug’ rational is to replace the harming pharmaceutical drugs by alternative ‘drugs’ and not least food of proven innocence but with documented health benefits as you indicate on your list though I go for much higher ‘therapeutic’ levels; roughly 10x regarding vitamin C and E.

      And basically I believe in the Hippocratic medical approach: “First of all do not harm!”, “Let your food be your medicine and your medicine your food!”

      Reply
  17. Martin Back

    Rheumatoid arthritis reduces levels of endothelial progenitor cells.

    Now I’m taking notice. I have ankylosing spondylitis, an auto-immune disease related to RA and Lupus. We have an elevated risk of heart disease and stroke, although some of that risk may be due to using NSAIDs and getting less exercise.

    At the age of 67 I thought the worst was over. My spine is totally calcified and a mild NSAID controls mild symptoms like restless sleep, morning stiffness etc.

    Then I got uveitis (a common side-effect of AS) and nearly lost my sight in one eye.

    The eye specialist explained that AS caused inflammation of the blood vessels in the eyeball, which permitted foreign matter to leak from the blood into the eyeball, obscuring my vision and causing other problems.

    Fortunately a course of steroid drops cleared up the problem and my eye is fine now. But it raised a couple of questions:

    1. Why get inflammation when I’m taking an anti-inflammatory? My GP said it’s because I take such a “piddling dose” (his words) of 25 mg indomethacin daily.

    2. How come the blood vessels leak? Presumably because I have a low EPC count and the damage to the endothelium can’t be healed fast enough.

    3. Why the eye and not somewhere else? Apparently the eyeball contains a type of collagen that people with the HLA-B27 gene (i.e. 95% of AS sufferers) produce, and which is targeted by killer T cells which mistake it for invading Klebsiella bacteria (the “molecular mimicry” theory).

    Reply
    1. JanB

      Hi Marin – re inflammation. I take turmeric capsules every day and they work a treat to take all the fire out of my psoriasis. If I leave them off for a few days it comes back. Maybe it’s worth a try.

      Reply
      1. Dr. Göran Sjöberg

        Jan,

        Funny, on my stove just in this very moment I have a pot with two tablespoons of tumeric powder in half a litre of water together a few pieces of ginger root simmering for about 20 minutes. This ‘innocent drug’ seems to have a extraordinary beneficial influence on the inflammatory status of the intestines of my wife.

        Though, hardly any profits for Big Pharma.

        I think this is also one of Mercola’s favourites.

      2. Gary Ogden

        Dr. Goran: I take my turmeric and ginger, grated whole-root, as an ingredient in the kimchee I make, and enjoy at breakfast, and sometimes supper, and my intestines are quite happy about it.

      3. Frederica Huxley

        I get a daily dose of turmeric and ginger – both minced root – along with garlic in my Golden Kraut. Hadn’t considered adding turmeric root to my kimchi!

      4. Gary Ogden

        Frederica: Golden kraut is a lovely name-turmeric gives such rich color to a ferment I have made something similar in the past. I make kimchi in part because I’m inordinately fond of onions, garlic, and chili, although two days ago I make a batch of kraut with cabbage, onions, and garlic. I ferment when the vegetables are ready for harvest. Like you, I enjoy my beet kvass, and I grow beets year-round; the climate here in California is amenable to that. I consider both the root and the greens essential health foods.

      5. robert lipp

        Dr Sjoberg.
        Thanks this “innocent drug” idea. After simmering do you take a teaspoon per day or what? I would like to move to my “own” concoction rather than buy supplements, any tips?

      6. Dr. Göran Sjöberg

        robert,

        We have been using tumeric powder as a spice now and then during the years but it has not been on a regular basis. My wife, with her intestine problems, has though favoured our use. She really likes the taste while I myself i am more neutral. This makes me wonder if there is a fundamental homeostatic “reaction” or physiological reason that has made her fond of this spice.

        Although, making a “drug” out of in this way is more of a “tea as a drug” approach. (“Let your medicine be your food!”)

        Anyway she drink a cup of it adding water to her taste an a cup which she then sips on, like I do on my C-vitamin glass of water, during the day.

        As always, life is an interesting experiment, which is also my present health approach, and by making own concoction you put yourself in control both physically and mentally.

        My professional life experience in metallurgical research tells me that if you are not really interested in a subject (i.e. applying a more open ‘holistic’ mental approach to your research) you are not to progress with any experimental activities. This attitude is what I find with Nobel laureates like Linus Pauling and Mr. Feynman who appeared at the end of Malcom’s last instalment in this great series. (Amazing number of comments there I must say.)

        Unfortunately, most of the research I have had the opportunity to scrutinise has mainly been of the type ‘more of the same’ which doesn’t add much of new ideas, ‘food for thoughts’, but rather confirm the consensus which per definition should mistakingly be taken for any “science”. The present trend to reuse experimental data from earlier publications with the help of powerful computational statistics is in this respect a very sad trend in my view. I tried the best I could to force my student back to the lab and away from the computer screens. The most important thing is though never to lose the perspective of what you are involved in. To guide students it is always a balance between ‘doing’ and ‘thinking’.

    2. Joe

      Martin, You might find a book called The Paleo Approach by Sara Ballantyne very helpful. It is not a diet book, but a study of what causes inflammation and autoimmunity in our modern diet and lifestyle and how to address it. Lots of good info on her website as well. She is a medical researcher who had many autoimmune diseases including AS. Her search of the medical literature in hopes of solving her own health issues led to a very comprehensive approach to “cooling off” the immune system and minimizing the effects of her diseases.

      A corollary is Dr Terry Wahls who took a similar approach to another autoimmune disease, MS and she is currently running a clinical trial on a similar diet and lifestyle approach that is apparently showing remarkable results in reducing symptoms in MS patients.

      I believe that gut health is critical to reducing inflammation and addressing autoimmune disease. Good Luck

      Reply
      1. Gary Ogden

        Joe: I fully agree. Gut health appears to be critical to human health. The gut microbiome is not only the major player in the immune system, but is in intimate communication with the brain, and appears to be, to some extent, in charge of brain function. It is not entirely hyperbolic to say that we are merely the housing for our bacteria, and they are truly in charge.

      2. JanB

        There is a wonderful book called “Gut” by Giulia Enders which is extremely informative and entertaining too about our innards. A thoroughly good read.

      3. Martin Back

        Thanks for all the suggestions. Dr. Göran’s concoction appeals to me. I love cooking up different things and trying them on myself.

        But the actual point I was trying to make related to the blood vessel leakage in my eye. When a blood vessel leaks, it must be repaired, and the repair is the starting point for clots/atheromas/plaques/fatty streaks, preumably.

        Previously, mechanical stresses such as turbulence have been advanced as a cause of endothelial damage, but in the case of my eye it’s an immune dysfunction. Another clue in the CHD mystery?

      4. Dr. Göran Sjöberg

        Martin,

        I am not an expert on what is going on in the bottom of our eyes except that the capillary vessels seem to get damaged when you turn diabetic and that you finally go blind. High blood sugar/insulin levels? Is it the same thing with the peripheral nerves and capillaries?

        Anyway, six years ago, my wife was suffering severely from peripheral neuropathy, her night vision had impaired so she could no longer drive her car at night and she was also diagnosed with glaucoma. Amazingly, when we look in the back mirror, our health care system couldn’t figure out that she was in a late stage of diabetes and she did that by herself by adding the pieces together. It was a ‘perfect match’!

        Realising this and converting to a very strict LCHF way of life, from one day to the other, most of her IBS symptoms incredibly disappeared in a few days. In half a year her night vision had returned and no glaucoma was to be diagnosed. An eye inspection about a month ago also confirmed ‘perfect health’ at the bottom of her eyes. In one year her peripheral neuropathy had also disappeared.

        To me a very strict LCHF could be worth a try for a couple of months if you have a serious health problem of an immunological character.

        I guess you have nothing to loose but perhaps a sweet tooth.

    3. Barry

      Martin,
      Recommend you try MSM (methyl sulfonyl methane). It’s extremely safe – unlike NSAIDS – having a LD-50 of approx. 20 gms per kg of body weight. For comparison table salt has a LD-50 of 2.5 to 3 gms per kg of body weight. There are many other benefits besides reducing pain. There’s a relatively old book (1999) “The Miracle of MSM” by Stanley W.Jacob, M.D, Ronald Lawrence, M.D., Ph.D., and Martin Zucker that provides plenty of info. Also see this http://hubpages.com/health/msmfacts.
      MSM is available from sports nutrition outlets as a bulk powder – better value than buying tabs etc. Has a bitter taste (smalll price to pay if it works) but you can add to any drink to mask the taste.

      Reply
    4. Mec Cham

      Hi Martin – from a fellow spondy ! It sure is one flippin disease plus the comorbidities, or potential for… I had to come off the NSAIDs, ruined my gut – now being told a possible stoma (Ha. No way – a potential for yet further problems). NSAIDs can also cause cardiovascular problems, see the papers put out by EULAR et al (European League Against Rheumatism – naff name). A lot of information out there re NSAIDs, now has many rheumies concerned :-
      Cardiovascular risk: Are all NSAIDs alike?
      http://www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)
      by N Pawlosky – ‎2013 – ‎Cited by 7 – ‎Related articles
      When duration of use was taken into account, an increased risk of serious coronary heart disease was associated with short-term use (<90 days) of ibuprofen …

      90 days of Ibuprofen is not that that long in the scheme of being a spondy. Yes, can control the inflammation to some extent and therefore the resulting ankylosis, but does not do that grand of a job and certainly not in the shape of the side effects !
      I have kept the worst of my inflammation under control with Low Dose Naltrexone. Low dose being 3.25mg. Have been on LDN for a number of years (10yrs?). Occasionally take a holiday from it, and then start back in with a very low dose, 1.25mg and work upwards to the 3.25mg : 4.75mg is considered an upper dose. Side effects for me have been nil (huzzah) but many find sleep disturbance a bother plus vivid dreams – am still waiting for dreams
      There are the biologics, and of course the potential for really nasty side effects, like MS; TB; Cancer etc etc. And if have actinic keratosis, do not take as will probably end up with lymphoma – am safe from having the biologics being pushed at me as have actinic keratosis (small mercies )
      So, back to my trusty LDN plus AAKG for the hypertension / vascular dysregulation and keeping sight in my one goodish eye (lack of oxygen caused severe retinal damage and therefore blindness in one eye). At least not faced with the bummer of a common spondy problem, uviitis / iritis. Another small mercy…
      Apologies Dr Kendrick and members, if this is a bit off topic. Take care all –

      Reply
    5. Mec Cham

      Martin – You might be interested in this from EULAR :-
      http://ard.bmj.com/content/early/2016/02/26/annrheumdis-2015-208194.full.pdf
      NSAIDs in Axial Spondyloarthritis : to be continued…?

      The rheumatologists are looking really hard at NSAIDs, and not a few are opining that ‘treat to target’ may no longer apply and that ‘take when needed’ may be as appropriate. After more than 10 years of not touching, I have taken one tablet, a Celecoxhib, due to rotataor cuff tear in one shoulder and a 10 yr old prothesis in the other shoulder causing problems = painful and inflamed. Anyway, interesting paper.

      Reply
      1. Martin Back

        I read the paper which seems inconclusive.

        I see no reason to change my NSAID. One 25 mg capsule of generic indomethacin does what I ask of it (peaceful sleep and no pain or stiffness), I can buy it off script, and it’s cheap at less than 3 pence UK per capsule.

        After many years of use I have never experienced any side-effects. Every time I buy a new supply the pharmacist warns me of possible gastric problems. As a result I am extremely careful to take the capsule with food, never on its own.

        But I have cut down from every day to every second day as a result of the warnings I’m getting here, and experimented with natural alternatives. I’m trying green tea at the moment, which seems to make no difference, and I bought turmeric powder and will boil up a Dr. Goran special soon.

    1. Robert Dyson

      I just started reading the full article. It starts –
      “Coronary heart disease is a tale of two forms of plasma cholesterol. In contrast to the well-established effects of “bad” cholesterol (LDL-C), the role of “good” cholesterol (HDL-C) is mysterious.”
      They have not read Dr. Malcolm Kendrick.

      Reply
      1. robert lipp

        Maybe this is connected
        I have read somewhere in my readings that raising HDL-C is not necessarily a good thing as some of the methods to achieve this do not raise the efficacy of the HDL-C. Meaning the numbers may change for the good but not the benefit.

        Any comments?

  18. Helen

    Many thanks for a series which has made fascinating reading. However, I wonder about the role of hypothroidism in CVD, as I’ve been told a few times over the years that it’s one of the major risk factors. Do you care to comment? Is the risk linked to poor mitochondrial function resulting from low intracellular T3? Or is the auto-immune action of the Hashimoto’s form of the condition (you’ve referred several times to SLE and RA) the most significant factor?

    I’ve been hypo-T since infancy, though the signs were only belatedly recognised in my twenties. There followed another 20 years of under-treatment courtesy of the NHS. Taking matters into my own hands has not resulted in straightforward progress: I appear to have developed peripheral insensitivity to thyroid hormone, which even huge amounts if T3 has not so far alleviated. It acts more easily on the heart though, which is going like the clappers and preventing any increase in T3

    I have other auto-immune conditions and last year I began to lose the use of my hands to RA. Luckily, I have a doctor (private) who prescribes naltrexone on the low dose protocol. It’s been a pretty effective immune modulator in this respect, and though I haven’t experienced the complete recovery some people report, I would not want to manage without it now. Better than methotrexate!

    Reply
    1. Jennifer.

      Helen, I am pleased you are getting help with your complex needs, although I do not understand the conditions you describe; I certainly wish you well.
      It does seem strange that in order to have a discourse regarding treatment, more often than not, we hear stories from patients resorting to the private sector. Why should this be? Has the NHS resulted in our medics being brainwashed? Even Consultant Physicians seem reluctant to encompass treatments being positively described on Internet blogs, but essentially not part of any conventional NHS, NICE guidelines.
      I repeat a question I ask periodically……is it the handing over of ready money that loosens the brain cells?
      The NHS is ‘free at the point of need”, not ‘free’. We have all paid good money for the service, and I am sorry that you have needed to resort to the private sector for the management of your poor health. In fact it is shameful, after all the effort that went into forming the NHS for the good of all members of our society, and we certainly appear to have a two tier system. I don’t blame you in the least for seeking help outside it, as I would do myself if the need arose.

      Reply
      1. PeggySue

        I’m sorry to say the NHS has to be there to treat the many these days. And there are SO many that in order to look after everyone to some degree, time is at a premium. The process is governed by calculated health economic models, statistics etc. When you think about it, that is all that can be done really. No time for a personalised service.
        One problem is (and it’s a biggy) is a lot of these models are based on what we now know to be flawed info ie low fat, linear models, de da de da de da. They are plainly wrong.
        The other problem of course is that the NHS is taken for granted (a large number of grown ups expect the doctor to act like some kind of parent) and the vast majority of people haven’t the foggiest how much everything actually costs. We think we’ve “paid our stamp” but we really haven’t. And what about all the folk that create a fuss if they aren’t given a prescription?
        I’m always staggered that gps in particular manage to give the level of care that they do. Many would love to do more, spend more time, but the system often does not allow it. I have seen gps have to leave their practice for not conforming.
        We are all so very, very lucky to have the NHS, warts and all. We have to empower ourselves to work with our doctors to make the most of the time they can spend with us.

        Rant over – I love the NHS!

      2. TS

        I would like the NHS to stop wasting money on unnecessary or dangerous drugs and the pharmaceutical companies to put more of their efforts into the search for new antibiotics – a really important issue – instead of fleecing the NHS. There might then be some money left over for the junior doctors and the nurses.
        My 92 year old mother takes around a dozen different drugs a day. She doesn’t really need the majority of them (in my opinion!) Actually she agrees with everything I say and does the opposite – because she has to have faith in her medicines and everyone involved with them. She
        takes metformin for her class 2 diabetes and eats sweets all day long.
        I have a good GP. I have high cholesterol (lucky me!) but he’s never even hinted at a statin. A friend asked him for a cholesterol test and he said, “Why do you want to know your cholesterol levels?” and they didn’t bother with a test. Nor does he dish out antibiotics, even when pressed for them. Unfortunately this makes him undervalued by a lot of his patients. No wonder some of our GPs have retired early (one went into farming) or suffered a premature death.

      3. Helen

        Jennifer, I could speculate endlessly and write reams on the subjects you raise. I’ve been ill most of my life, so I’ve had ample opportunity to observe the average medic. It is the culture of those at the top of the profession to recruit people who resemble themselves, thus enabling a certain institutional mindset to endure, one that does not tolerate individuals with enquiring minds. I’ve known several doctors who have suffered censure by their colleagues, simply for the application of scientific principles to their practice, and their persistence in asking awkward questions.

        I agree wholeheartedly with your sentiments about the NHS; I worry about the future, and whether I will be able to fund all this private treatment into my later years. Thank you for your good wishes.

      4. Sylvia

        The health and social care act of 2012 saw the death knell of our fantastic NHS. Sorry to get political but with an internal market it is profits before patients. The medics now working in this upheaval are totally undervalued and demoralised. Apologies for straying again from your wonderful blog Dr Kendrick.

      5. Jennifer

        Yes, Sylvia, like you today, I tend to err on the political aspects of some themes posed on this wonderful blog….and my answer to those who deny political involvement in life…. ( and denials seem to be worn as a ‘badge of honour’, for some obscure reason)…..from the first breath you take in life, you are involved in politics, and to deny such is illogical, and head-in-the-sand thinking.
        I love our NHS, and respect all who work in it, having started there in 1965……within the first day, us students ( who thought we were the bees knees in our white coats) had it drummed into us, and it has never left me, that we were but one small cog in a very large wheel….each speciality dependent on one another, from the bottom to the top ( work out who sits where on the ladder), and that political intervention must never be disregarded in NHS management.
        Sadly, the politicians are running the show to the detriment of the patients and workforce.
        Oops….should have listened to my lovely mother…..”don’t talk money, religion or politics”…you will just get upset.

    2. Mec Cham

      Helen – Quote : I have a doctor (private) who prescribes naltrexone on the low dose protocol. It’s been a pretty effective immune modulator in this respect, and though I haven’t experienced the complete recovery some people report, I would not want to manage without it now. Better than methotrexate!”
      Ahhhh. My old ‘friend’ LDN – low dose Naltrexone. I also take LDN Helen. I have AS (ankylosing spondylitis) inflammatory spine disease (that can come with a range of comorbidities), in the arthritides complex. Efficacious medication. Just wish that NICE would recognise, but being as cheap as chips (or even cheaper !) pharma won’t make a penny out of it, so LDN has been sidelined. It is the same as diet for the arthritic diseases, inflammatory foods v. non-inflammatory foods, and low or no starch for treating AS – this being Prof Ebringer’s seminal work back in the 80s (Prof Ebringer, now retired, was head of rheumatology at Kings, London). Ebringer has been howled down in his time, then suddenly…the Human Microbiome Project and gradually ‘diet’ as a concept in treating the arthritic diseases is slowly being recognised ! Diet = gut, the second brain = brain : all linked. Ebringer exonerated, though the die-hard rheumies still refuse to recognise his work (GGgggrrr) and acknowledge that starch – and diet generally – plays a big role in these inflammatory arthritic conditions.
      Apologies Dr Kendrick and members, getting carried away again.

      Reply
      1. Helen

        Glad to hear LDN is working for your AS. I was aware of the AS link with diet too. As ever with the medical profession, when they eventually accept a ‘radical’ or ‘fringe’ idea, they behave as though they’d never heaped scorn on it!

        I see a Prof of Gastroenterology (NHS) about some chronic gut issues. He is actually enthusiastic about my taking naltrexone, because he’s aware of research in his field using other anti-opiates – patented ones, costing a lot of money. Was he willing to prescribe me LDN on the NHS? Of course not!

  19. Don

    Does a persistent course of Niacin (real, not “no flush”), for example, 500mg 3x per day, positively affect eNO?

    Reply
  20. Randall

    L-arginine is being mention here. Do not rush out and buy plain L-arginine,
    because L-arginine without the correct synergists
    and co-factors or an improperly prepared L-arginine
    formula can cause reactivation of the herpes virus
    as well as the stimulation of peroxynitrate. “push their L-Arginine levels above normal as it will likely worsen one of the root causes of their condition.” http://www.medicalinsider.com/cardiac3.html and https://books.google.ca/books?id=XE77AwAAQBAJ&pg=PT186&lpg=PT186&dq=l-arginine+produces+peroxynitrite&source=bl&ots=iyiiPSMv3b&sig=8pP-Kd3hn8ZLnEaKzZkg95oH5mk&hl=en&sa=X&ved=0ahUKEwjpp_-QlLnLAhUBeCYKHf_8DhwQ6AEIRDAF#v=onepage&q=l-arginine%20produces%20peroxynitrite&f=true Look into AAKG.

    Reply
    1. Gary Ogden

      Randall: I’ve read both of these resources, but haven’t found anything about synergists or co-factors. Is there an available resource for selecting an L-arginine supplement?

      Reply
      1. Mec Cham

        NO – The Arginine Solution : “The Arginine Solution, A Few Grams of Prevention” by …
        http://www.ofspirit.com/tw-theargininesolution.htm
        The Arginine Solution: The First Guide to America’s New Cardio-Enhancing Supplement by Robert Fried, Ph.D., Woodson C. Merrell, M.D. and James Thornton.
        Validated in 1998 by the Nobel Prize in Medicine.
        AAKG – Alpha Arginine KetoGlutamate is available from multiple sources, from capsule to powder by-weight. This latter from iHerb. For capsules, Swanson and Doctor’sBest (600mg) are excellent, no unacceptable additives – I have used both brands. At the moment am on Swanson, Ultra, capsules, 1000mg. Always check ingredients of the various brands in supplements. BigVits in the UK are a responsible supplier. For the USA Life Extension has an excellent reputation, but is expensive.
        I take L’Arginine for vaascular dysregulation and for spiking blood pressure – spikes from 132/70 to 227/115 (this last was my highest). Yes, have tried 16 different anti-hypertensive medications, all produced horrific side effects. Arginine seems to be the answer. In *addition, I also suffer from Not Tension Glaucoma (NTG). NTG is a vascular dysregulation, see Flammer Syndrome. Prof Josef Flammer, Berne is a glaucoma specialist. His son is a consultant cardiologist. They have done massive research in NTG glaucoma. Interestingly, it is now found that many with NTG ALSO suffer from irregular heart beats and heart problems. (This is apart from Raynaud’s, peripheral neuropathy, Erithromelagia, stasis dermatitis etc etc). Yes, I have irregular heart beats and a long QT interval – and all the rest : a classic Flammer Syndrome case, excepting for the BP spikes, but years ago had low BP. (I have been advised to find a vascular cardiologist.)
        Due to the dysregulation, I have now lost the central vision in my right eye – insufficient blood flow to the retina. Am hopeful that stem cells might at some future date, help. The only positive factor in being clinically blind in one eye is that the bifocal double vision is now under control ! The Vl nerve in the right eye shows paralysis.
        All-in-all, this is great fun, not ! Now add in ankylosing spondylitis to the mix. And the usual NSAID damage to the gut – cannot touch NSAIDs ever again. Gut is ruined, and have recently been threatened with a stoma – no, not going there. Frying pan to fire as far as I am concerned.
        Meantime, no meds, rely on supplements and herbs – tumeric and fresh ginger root being my staples, plus the L’Arginine. As for diet, low starch (Prof Alan Ebringer’s seminal work 1982, for treating AS and RA). No nightshade family and no cruciferous family. No red meat. In other words, keep away from inflammatory foods, and Oh yes, blasted fibre. Fibre is a killer.
        Apologies for the tome, but the comments have been so fascinating that I felt my own little histoire might be of interest / use. Love Dr Kendrick’s treatise – superb.
        Take care all – have a good week-end.

      2. Ben

        how much l-arginine do you take and how long did it take to show it was working. My blood pressure is all over the place. On two meds but would like to come off those. Did you stop taking your meds on your own or with your docs consent. Did you go cold turkey.

      3. Mec Cham

        Ben – huge computer problems here (my ancient desk-top needs a radical overhaul).. Anyway. As mentioned, I take 1 capsule per day 1000mg Arginine AKG, capsules from Swanson. It has definitely kept my BP from leaping all over the place. My GP and I are pleased to have it in the range of 140/90 – 160/95. Sometimes it does go out of range, to 187/100, but not too often (now) and not as it did before *sticking with the AAKG. In addition, the palpitations have calmed down immeasureably.
        As for the anti-hypertensive meds, no, as soon as the side effects happened up, I pretty much stopped taking. One gave me such double vision that everything turned double. Took 3 days to get out of my system. Others were appalling dizzy turns, so as not able to walk without support to not leaving the house at all. Others were nausea, tinnitus – bells clanging at midnight are not my idea of fun !! You name the side effect and I just about suffered from it !! It is very difficult for me to take medications. Believe my ancestry : Celt, with a touch of the Viking (Highlands invasions etc etc) red hair, very freckled and pale eyes gives rise to a reactive body (Don’t stand much of a chance )
        Cannot say I went ‘cold turkey’ as could not take any of the meds for long enough, they made me so darn sick. But the AAKG seems to do the trick quite nicely. Yes. Would be good to get better control, but that aint gonna happen – not unless they come up with other newer, meds that don’t cause such horrible reactive side effects.
        Betroot juice is said to be excellent for elevated BP, but I detest beets, but might suit yourself. Not sure that taking AAKG plus beets would be such a good idea… You would have to discuss with your medicine traitant.
        As for AAKG side effects, a poster here mentioned herpes. Yes, IF are carrying the herpes virus then will, could, give rise to a herpes outbreak. But TG I do not carry that virus and have never had chicken pox nor ever been vaccinated for chicken pox. AAKG suits me fine, no bad side effects, just keeps my BP from leaping up to 227/115. But even at that spike did not feel as bad as when I took the anti-hypertensive meds.
        Hope this has helped – take care, go well

      4. Ben

        Thanks. Whats the difference between arginine akg and just plain old arginine? There is a big difference in price.

      5. Mec Cham

        Ben – L’Arginine v Alpha Arginine KetoGlutamate ; is Arginine AND Arginine-ketoGlutamate – see :-
        http://www.livestrong.com/article/441457-what-is-difference-between-l-arginine-l-arginine-akg/

        More information : “L-arginine alpha-ketoglutarate is a 2:1 salt formed from the combination of two parts arginine and one part alpha-ketoglutarate. This supplement is popular among athletes because it helps with the synthesis of amino acids, and the creation of nitric oxide, making more proteins available to the body during exercise cycles. L-Arginine is a type of amino acid that does work to maintain the integrity of the skin, joints, liver, and muscles. It also helps in maintaining good levels of blood sugar, hormones, and keeps the immune system functioning well. Arginine is one of the rare amino acids that is considered semi-essential because though the body can manufacture perfectly appropriate amounts of the acid to keep up to normal amounts, every once in a while it may be necessary to supplement it. Arginine is able to support the immune system through its ability to produce T-cells and it is also supportive of the liver in that it is able to rid the body of toxins. Urea is needed in order for the body to expel ammonia through the urine however; urea would not be manufactured without arginine. Arginine is also helpful in releasing insulin when necessary and in creating and facilitating the creation of important hormones. Arginine helps to stop the restriction of blood flow throughout the body. It allows blood vessels to relax rather than be constricted, dilating them so that there is better flow of oxygen throughout the body.”

        If you put your question into an internet you will find much information.

        AAKG is very interesting. Has been used to great effect in treating a particularly nasty systemic disease in horses : DSLD / ESPA, degenerative suspensory ligament desmiotis / equine suspensory proteoglycans accumulation; can be seen here in this excellent 5 mins video presentation : https://www.youtube.com/watch?v=7YXTxvTEJFo It was Dr Eleanor Kellon in her seminal work on treating the disease who came up with AAKG plus the ‘J’ herb, Jiaogolam, which boosts the good effects of the AAKG. DSLD / ESPA cannot be cured, but the condition can be managed, much like ankylosing spondylitis (AS) and RA cannot be ‘cured’ but can be managed. Some horses have had reasonable quality of life (QOL) for several years before eventually having to be put down. In the end it does come down to doing the kind act !

        BUT, AAKG+ the ‘J’ herb is amazing. Does help with inflammation and does help in blood flow. IF going that route, please check carefully with your GP and do your own research as well – needs to check if taking other medications for counter indications etc etc. Also, should you take this route then be careful of which brand you use, and which supplier you use – there are arguments against using Amazon ! Always check the ingredients as some brands carry adjuvants that best to steer clear of. As have said before, Solgar; Doctor’s Best; Life Extension; iHerb – are good. Have used all of them. Am presently using Swanson at 1000mg – this is specifically to help oxygen to my eyes and to help with this tedious hypertension. When I have finished this high dosage I will be taking Doctor’s Best at 300mg, 2 capsules = 600mg.
        Again, hope all this helps – take care

  21. TS

    Is this of interest when we consider food, lack of food, and longevity? I know there are always the exceptions but…
    We hear today that Yisrael Kristal is the oldest man alive at 112 years. And a concentration camp survivor! I am anti excess sugar as much as anyone but it’s rather ironical that Kristal was an expert “candy” maker.
    Alice Sommer survived a concentration camp and lived to be 110 years old! She was a pianist who was allowed to play in the camp. She said that she was happy when she had a concert and that music saved her life and prolonged the life of those allowed to listen to her.
    Prison food doesn’t seem to have shortened Nelson Mandela’s life and he certainly had a zest for and purpose in life didn’t he?

    Reply
    1. robert lipp

      Unfortunately, there will always be the exception that make the rule. Maybe it’s in the genes or maybe it is something in the water, who knows. You are probably nearer to average, then again you may be the exception. We, you and I, will find out that we are exceptional in 30 years when we hit 100. 😊

      Reply
    2. Martin Back

      I know a pharmacist who did locum work at prisons sometimes, and he had dealings with Nelson Mandela. He told us he wasn’t allowed to say what went on in prisons due to the Official Secrets Act, but there was no chance of Mandela ever lacking the best medical treatment. (This was in the latter years of his imprisonment. Maybe in the early days it was different.)

      But the concentration camp survivor story is interesting. We know from autopsies of people who lived on starvation rations in WWII that they had almost no plaques in their blood vessels, but once they returned to their normal diets they got the accustomed number of plaques.

      It was as if the body had scavenged every scrap of fat to avoid starvation, but relaxed its efforts once food became plentiful again.

      Many people living close to nature have a “hunger season” or actual famine conditions sometimes. Which makes me wonder if their heart health is due to hunger rather than a more natural diet.

      Reply
  22. robert lipp

    Dr Kendrick
    I know that you cannot read all and respond to many. Yet, I rack my brains and re-read (especially your erudite regulars) in the endeavour to find an innovative question that piques your interest to respond. Sometimes, Oh joy I hit the jackpot! 😀

    A question: beetroot for nitrates for NO or even eNO for endothelial repair has a conundrum as beetroots are on the LCHF “Red” list {Prof Noakes: Real Meal Revolution}. So does that make streaky bacon with nitrates a good alternative source leading to eNO?
    Especially, as I am now refusing Statins and have come off blood pressure meds {before was about 95/65}. I have to find natural alternatives to forced meds that appear to be rather limited to symptomatic treatments only.
    Thanks

    Reply
    1. Gary Ogden

      robert lipp: Pardon me for butting in, but I take my beets (and some other vegetables, fruits and dairy) in the fermented form. I believe the Lactobacilli convert the bulk of the sugars to lactic acid (or some such as this), lowering the glycemic response. I may wrong about this, but it makes sense to me.

      Reply
      1. Helen

        Gary, do you have an idiot-proof method for fermenting vegetables? I’ve tried making sauerkraut as an aid to recovery from chronic gut problems, but it always develops mould, no matter how careful I am!

      2. Frederica Huxley

        I would recommend Sandor Katz, Wild Fermentation, followed by an excellent group on Facebook with the same name. And, always weigh down your kraut under the brine to stop mould.

      3. Gary Ogden

        Helen: As I understand it, there are two ways to do a successful ferment: with or without whey. Since whey is easy for me to make, and always successful, I always use it. You must start with raw milk (easily available here in California, and in many European countries). I buy a bottle of skim (only use skim for this purpose), leave it on the counter for 1-4 days until it separates, then strain it through a tea towel/colander into a pot, hang the towel up to drip a few hours, squeeze out the rest, and decant into jars to store in the fridge. One quarter cup (60 ml) per quart/liter is the dose, along with 1 Tbs./15 ml sea salt. I used to slice the cabbage fine with a knife, but now use the food processor (apparently the traditional German method involves two people with a large mandoline over a barrel, sprinkling with salt and mashing down with their feet from time to time), then I beat it in the bowl half to death with a wooden mallet, until lots of liquid is released from the cells, add the whey, mix well, and fill the jars. Three days on the counter, then refrigerate. I’ve eaten it after a year-just gets better. Captain Cook, on his second voyage, had one barrel left after two years, and twice crossing the equator. When they made port in Lisbon on their return home, the local officials tasted of it, and insisted on keeping it. Apparently to ferment without whey involves doubling the salt. Sometimes a ferment get a white coating on top. This is not harmful, so they say. I just spoon it off. Make certain all the vegetables remain submerged under the liquid (sometimes I open the jar and push down what has crept up). Leave 1-2 inches (3-5 cm) head space in the jar, for it will grow. An excellent resource is Sandor Katz “Wild Fermentation,” and “The Art of Fermentation.” I’ve had a few failures along the way, but only rarely. Hope this helps.

      4. Dr. Göran Sjöberg

        Helen,

        Here is a “fool proof” way of succeeding with sauerkraut – anyway it has worked excellently a number of times for me.

        Buy an organic (important since pesticides kill your bacteria) cabbage head to start with

        Mince it fine – there are nice kitchen machines to do the job

        Put the chops on your kitchen table and add a liberal amount of salt

        Massage the heap with your hands until it starts juicing – the salt pulls the juice out of the cabbage. In this process the beneficial bacteria who are going to do the fermentation job enter.

        Get a nice sturdy jar and press the cabbage chop hard with your fist into the jar

        An – now this is important – the juice has to cover the surface well; otherwise you have to add some water and for sure not chlorinate from the tap but from a bottle. If the surface is not covered by juice the cabbage will get mould rot and get ruined.

        Take a plastic bag of reasonable size and fill it with water and have the bag to cover the cabbage in your jar

        Leave som space since the cabbage will swell during the fermentation (I put the jar in a pot so any excess juice is collected)

        Let it stay for a week or so on your kitchen table and check the process now and then and press down the cabbage if it rises to high

        The most important part is that the surface is always covered with juice so air doesn’t get in – add water if necessary. The plastic bag with water is here the “fool safe” air tight lid.

        There should be a great good sour smell when the fermentation has calmed down and it is time for the refrigerator.

        Good luck; if I did it anyone can do it 🙂

      5. Gary Ogden

        Helen: One minor but important point: if you use canning jars, as I do, don’t screw the lid on tight until the initial fermentation is finished (3 days or so), and you’re ready to store them in the fridge. Co2 buildup can irreparably crack the jar or lead to something more exciting.

  23. Andrew Boot

    I work in medical research (rheumatology) in a university hospital in Madrid. It is true that a high number of patients – RA and SLE inclusive – end up as coronary deaths. The process seems to be – first, stop disease progression (fine), then, stop infection (fine) then die of CVD (no solution so far). My hypothesis is that SLE patients tend to be subjected to dangerous levels of Prdnisone or other cortisol which then repercutes. So the question is: is it the disease that gives rise to CVD? or the treatment of the disease?

    Reply
    1. Dr. Malcolm Kendrick Post author

      Andrew. I think that is a very good question. My main hypothesis about CVD was (and mainly remains) that it is due to dysfunctional HPA-axis with concomitant overproduction/dysproduction (if that is a real word) of cortisol. I think steroids are a major driver of CVD, and in general anti-inflammatories accelerate CVD. So I am certain that cortisol plays a role in the high rates of CVD found in SLE and RA. However, I think the vasculitis found in both conditions is also highly important. However, disentangling the two possible causes is tricky.

      Reply
      1. Jennifer.

        Now that is interesting about NSAIDs.
        In the 1970s my father had awful osteo arthritis, and was prescribed Ibuprofen, (I believe it was prescription-only then).He complained bitterly about the effects on his gut, but needed pain relief as he had a hard, cold, manual job, ( which probably contributed to the knee-distorting arthritis). Some years later, aged 62, he had a heart attack, which hospitalised him for 2 weeks, ending his working life, and thus ensuring he never achieved the goal of collecting his meagre old aged pension.
        He had never smoked, he drank very little, ate a decent diet, was athletic in his youth…..in effect, he had no obvious cardiac risk factors. Maybe it was the NSAIDs he had taken, in the highest of dosages permitted, over a prolonged period? The fact that he was diagnosed with motor neurone disease at the time of the heart attack, is a side issue, I believe.
        I have an instinctive aversion to using NSAIDs, and would need a convincing reason before using them …..due to the effect on the gut…….but the cardiac link is most interesting, albeit 40 years after my father’s experience.
        p.s. as is the case with my contributions, they are purely anecdotal, and lack scientific scrutiny. I hope that they may still be of interest in supporting various hypotheses outlined by practicing researchers.

      2. Dr. Malcolm Kendrick Post author

        I call medical anecdotes ‘case histories’. Sounds much more scientific, you can even publish them. All the best medical research starts with case histories, or accidental observations. Unfortunately, medicine has been taken over by double blind placebo controlled medical studies, and no other evidence shalt be allowed – by order of the management. Slight problem, the only group that can afford to do such massively expensive research are the pharma companies, and they only do research with one end in mind. To make money. Which means that there is most certainly a degree of bias built into the evidence base. Some may even feel the bias is so great that we cannot believe anything we read anymore.

      3. JDPatten

        Case history:
        A few years ago I popped a bunch of ibuprofen as a sore-muscle preventive. I was hauling cords of firewood out of my woods with a wheelbarrow. It worked. No sore muscles.
        However, it was the cause of a nasty case of lymphocytic colitis. (Originally misdiagnosed as Crohn’s.) Ugh!
        It took a year to calm down.
        It’s triggered if I take a single dose.
        Never again.

      4. JDPatten

        Hm.
        Might a person be hypersensitive to ibuprofen?
        Might it be responsible for severe cardiovascular disease as well as gastrointestinal problems at “normal” dosing?

      5. Dr. Göran Sjöberg

        As a successful anecdote, oops “case”, I tend towards not believing anything I read if i suspect Big Pharma is luring in the shadows. The main problem is to unveil what is going on in those shadows.

      6. B

        So do you believe a dysfunctional HPA-axis can be fixed with quality sleep – diet – less stress – exercise ? Which would lower cortisol levels – what levels would you say are healthy ? Interestingly you talk about steroid/anti-inflammatories could asthma inhalers contribute to CVD?

      7. PeggySue

        In reply to B asking if asthma inhalers could contribute to CVD – I would think being the type of individual that has an inflammatory condition such as asthma is not ideal in the first place. It can easily be a life threatening condition.
        All about balancing risks. If I didn’t manage my asthma effectively I wouldn’t be able to exercise regularly, sleep properly etc etc. Goodness knows what that would do to my HPA axis. Unfortunately I have to use inhaled steroids to do this – I just try to keep them to a minimum.

    2. Jennifer.

      Andrew, in my response to you, please cast an eye on my contribution today at 4:01pm. There may indeed be more than a passing link between CVD and medications given for non-cardiac related conditions. Is it perhaps because we have not thought to look for them?
      There are examples where meds given for one system cause trouble in another system.
      Let’s face it…..statins given for so-called cholesterol dysfunction (which I regard as probably very rare), have been shown beyond doubt to detrimentally interfere with the musculoskeletal system and glucose metabolism. It seems logical therefore, that some meds could affect the the heart and / or cardio vascular system.
      Don’t get me wrong, there are medications which are most beneficial to life, and which we are prepared to accept unwanted side effects, but we seem to be encouraged to take concoctions at the behest of lobbyists, which merely line the pockets of big pharma, drain the NHS of resources, and use the public as guinea pigs.

      Reply
      1. Mec Cham

        In response to JD PAtten 12/03, Quote : “Might a person be hypersensitive to ibuprofen?
        Might it be responsible for severe cardiovascular disease as well as gastrointestinal problems at “normal” dosing?”
        (Cant see where to respond to JDP…) Yes. One can indeed be hypersensitive to ibuprofen, not only with a reactive gut but also cardiovascular. This is recognised by rheumatologists. For myself I cannot tolerate the NSAIDs but can tolerate the *very occasional celecoxhib. IF on NSAIDs it is strongly advised to take a stomach protector – usually in the shape of a PPI, Hmmmm. Rather, take with food…!!

  24. Jon from Virginia

    Dr Kendrick, you said “Anything that increases NO levels in endothelial cells and also helps to protect them from damage appears to increase EPC production in the bone marrow.” Does that mean the newest heart medicine might be… low dose or slow release .. umm.. Viagra?

    Reply
    1. Dr. Malcolm Kendrick Post author

      Well, it started as a heart medicine. It is also used as a heart medicine in pulmonary hypertension. It can also be used by mountaineers to prevent altitude sickness. So, yes, possibly.

      Reply
  25. michael goroncy

    To address some of the commentators concerns in this part v111 series.
    Purely from an observational (not confirmed ) viewpoint.

    (1) Regarding ‘NITRATES’…..”When it comes to food, vegetables are the primary source of nitrites. On average, about 93% of nitrites we get from food come from vegetables. It may shock you to learn that one serving of arugula, two servings of butter lettuce, and four servings of celery or beets all have more nitrite than 467 hot dogs. And your own saliva has more nitrites than all of them! So before you eliminate cured meats from your diet, you might want to address your celery intake.” Although regular consumption of ‘small-goods’ is not a healthy nutritional option.
    So! if you are concerned about nitrates…you don’t have a problem. Find something else to worry about that does matter.
    (2) NSAIDs….no news flash, been known for over a decade. Short term gain/long term pain. Just don’t consume them.
    (3) Statins (again). Secondary prevention only. If the ‘side effects’ are debilitating, stop taking them. Problem solved. Sure, problems may appear after many years. Deal with that if it happens.
    (4) Nitric Oxide: Became interested in this exactly 9 years ago, and went in search of the ‘Amino Acids’ involved. Pretty slim pickings. Went ‘Googling’ and found a small/sole operator who I corresponded with by email. He seemed to know his s**t . So I rang him. I live in Australia, he is based in Oregon USA and imports all the ingredients from China. I was concerned that he sourced from China. He explained that over 90% of the Worlds supplements are sourced there. He has currently built his business to over 20 employees and has 2 local labs that test the quality of all ingredients, which he imports by the ton.
    I rang him and spoke for over an hour. His 8 yo son had ‘Pulmonary hypertension’ and he was treating him with 6 times the dose of ‘Sildenafil’ viagra of an adult. His wife was a physician. These people seemed to be on the ‘Cutting edge’ of chemistry. Again, this was 9 years ago. I pay 1/3 to ½ less for all my ‘Amino acids/vitamins’. I cannot vouch for the quality or disclose my supplier….’seek and you shall find’.
    (5) COQ10 … as you know, with age and use of statins, the deletion can be rectified by supplementing. Here is a useful recipe:

    Coconut Q10 (Coenzyme Q10 & Coconut Oil Recipe for Increased Bioavailability)
    1. Heat 16 fluid ounces coconut oil to between 100°F (38°C) and 110°F (43°C) in a sauce pan on the stove.
    2. Add 25 grams Coenzyme Q10 powder. The powder will melt instantly and dissolve into the hot oil.
    3. Stir for one minute.
    4. Remove from heat and allow to cool to between 80°F (27°C) and 90°F (32°C).
    5. Pour mixture into a rigid plastic or glass resealable food storage container and allow to cool to room temperature.
    6. At below 76°F (24.4°C) coconut oil will turn solid, but that’s alright.
    7. The blended oil should be kept sealed but refrigeration is optional.
    8. A level half teaspoon of this oil, liquid or solid, will net approximately 130 milligrams Co-enzyme Q10, which is in the usual range of a commonly recommended serving size for this most bio-available form of CoQ10.
    9. Do not exceed a serving size of 1 level teaspoon (260 milligrams) of the blended Coenzyme Q10 coconut oil per day, except under the care and supervision of a physician.
    10. Take your CoQ10 preferably with a fatty food at meal time. You may spread it on toast, or add it to any food like you would as if it were butter.

    This 16 fluid ounce recipe will net 96 level teaspoons, or 192 level 1/2-teaspoons, enough highly bio-available coconut oil dissolved Coenzyme-Q10 for more than a 6 month supply.

    Reply
      1. michael goroncy

         Coenzyme Q10 (also known as ubiquinone, ubidecarenone or CoQ10) which is an oil-soluble substance is present in most eukaryotic cells, primarily in the mitochondria. CoQ, or Q10 is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way. Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney—have the highest CoQ10 concentrations. 

        There are three redox states of coenzyme Q10: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in the electron transport chain and as an antioxidant respectively.

        PureBulk’s Coenzyme Q10 is a 100% natural product that is manufactured from corn as the starting material. 

        It is vital supplement if taking statins. Very few, if any GP’s advise patients of this necessary supplement which makes it a culpable act, which you can file under bad and inadequate advice to the detriment of patients.

        While on the subject of supplements, it is worth keeping in mind: that the body cannot distinguish between a natural or synthetic form of any vitamin.

        Some readers here are interested in ‘Turmeric’ (active ingredient being ‘Cir-cumin’). Don’t waste money on buying it at huge mark-ups from vitamin companies. Buy from an Asian/Indian grocer for pennies.

      2. Mr Chris

        Hi Michael,
        On the subject of Coenzyme Q10, my lipids guy always told me there was no valid publication of it having any effect whatsoever.

      3. Frederica Huxley

        Whateverm form of turmeric you use, it is a good idea to add at least a pinch of black pepper – it will do wonders for the bioavailability of the spice!

      4. Bob Niland

        re: …Coenzyme Q10, my lipids guy always told me there was no valid publication of it having any effect whatsoever.

        Ask him, then, why Merck, in 1990, took out U.S. patents 4,933,165 and 4,929,437, covering statin formulation with CoQ10. They never brought it to market, and the patents prevented anyone else from doing it either.

      5. Dr. Malcolm Kendrick Post author

        Statins severely reduce Coennzyme Q10 levels. Merck knew this, and clearly saw that it was a problem. They decided not to market statins + conenzyme Q10 for reasons that can be easily guessed at. when a lipid guy say there was no valid publication of it having any effect whatsoever, he probably means a ten thousand patient double blind etc five year study. For a product with no patent protection… that would interesting.

    1. Mec Cham

      In response to Michael Goroncy – Coconut Oil – excellent. Can eat it, can cook with it – stands up to a high heat – can put on body and on hair. Multitude of uses and is soooo good.
      Re the CoQ10 – like yr recipe. Combines best of both worlds. I am taking Ubiquinol 100mg Healthy Origins, softgels, natural, soy free, non-GMO. Supplier, BigVits in the UK. I particularly like BigVits, who are not only efficient and pleasant to deal with, but one can telephone in ones’ order, one is not obliged to ‘order on-line only’ – a *huge plus for me as I refuse to order anything on-line (too dangerous, no matter what they claim !) Also, BigVits stock good brands and full ingredients are given for each item. They also stock coconut oil :))

      Reply
  26. Danny Evatt

    For those that are interested; Just received my blood results after 9 months of a modified Paleo diet, increased exercise and supplements of Niacin, Garlic, Magnesium, Vit. C,D,K(MK-7), Fish oil, and L-Arginine. Also started giving blood every 8 weeks for a future reduction in my higher than normal iron levels.

    Lp(a) down 40%, Triglycerides down 28%, HDL up 18%, total chol. (as if it matters?) down 19%. Next test (in Summer) another arterial Calcium scan. The results should show (due to the addition of higher supplemental levels of vitamin C and MK-7, as will be suggested by the good doctor I suspect) either a reduction in Calcium deposits (is this possible?) or at minimum a lessening in the growth (avg. 12% over the last 5 years).

    Nothing like being a test subject using your own body! No Statins, stents or Rx blood thinners for me… 🙂

    Reply
    1. BobM

      For me, after over two years of low carb, high fat (eat as much fat and particularly animal fat per day when I eat) and intermittent fasting, HDL increased over 40%, triglycerides decreased over 40%, total cholesterol about the same, LDL a little decreased (difficult to tell, since it’s calculated anyway), hemoglobin A1c down (to 5.2), fasting blood sugar down. I don’t have a good read on Lp(a) or LDL-p or ApoB, as some of the tests were “normal” fasting (after 12 hours or so) and two were extended fasting (4.5 days, yes DAYS). The fasting for that long messes up the values too much, but since I have to pay for the fancier tests, I can’t pay for them both before and after fasting for an extended period.

      Reply
  27. Odette Hélie

    About statins, the fact that they are practically useless in primary prevention et not spectacularely useful in secondary prevention still stands in my opinion (if clinical studies are to be believed). Those who tought it was workig through its antiinflammatory properties will find this explanation elegant, but still, statins are no miracle cure !

    Reply
  28. Gary Ogden

    I’ve done a Pub Med search of L-arginine in hypertension, and found what I think are two intriguing and related clues. One paper shows that L-arginine supplementation has only a modest effect, at best, on people with normal BP, but a significant effect on those with BP greater than 130/85. Two other papers show that L-arginine supplementation has little to no effect on endothelial function for people with low levels of ADMA (asymmetric dimethylarginine, a competitive inhibitor of L-arginine metabolism by NO synthase). They found that L-arginine therapy restores the L-arginine/ADMA ratio to normal in those people with high levels of ADMA, and thus normalizes endothelial function. This begs two questions in my mind: 1. What causes high levels of ADMA? and 2. Is this out-of-balance ratio a major cause of hypertension? I shall keep looking, since its a rainy day.

    Reply
      1. Gary Ogden

        Ben: I don’t have the precise numbers at my fingertips, but one paper said that 3-8g/day is a safe dose; another I believe used about 12g/day in a divided dose, three times per day; and a third had a placebo arm, a low-dose arm, and a high-dose arm-only the high-dose arm showed benefit (I believe on the order of 20-25 g/day). But, as Dr. Kendrick says, we must read the literature with a skeptical eye, and read lots of it, in order to discern what might be relevant, truthful, and useful. What interests me now is how the L-arginine/ADMA (asymmetric methylarginine) balance gets out of whack, and how to fix it. Craig’s reference provides some interesting clues, and I will continue looking in Pub Med (only 133,988 results to go).

      2. Gary Ogden

        Addendum to my reply to Ben: I’ve gone back to the paper which evaluates L-arginine in hypertension, which found significant reductions in both systolic and diastolic BP after four weeks only from 12g per day, in three doses, and not from 6g or placebo. Now I’m interested in AAKG, from Mec Cham’s interesting comments, though she’s taking only 1g.

      1. Mec Cham

        Well – thought that my posts had not been put up as I only find one, and that a rather old one. So, looks like I may be better off with increasing my AAKG – no problems. Will do so forthwith. Will be most interesting to compare higher dose with the lower dose. Will titrate gradually – have my own tonometer.

      2. Mec Cham

        Thank you Dr Kendrick. Found my ‘comments’ this morning. Know they were not solely ‘on-topic’, but hoped of interest anyways. Love this series – am telling friends and family to get acquainted pdq : have even told my gastroenterologist… Am seeing a new cardiologist in April, and hopefully she speaks good English, in which case I shall definitely be directing her attention to your superb site. (I live in France, only a few of the medics speak English).
        Again, my thanks Dr Kendrick –

  29. bill

    Dr. Kendrick:

    Would you recommend replacing ibuprofen
    with aspirin in the case of a common headache?
    I have salicylate sensitivity. What could I use
    for a headache?

    Reply
  30. mikecawdery

    Dr Kendrick,

    Another excellent article in this epic series. Please keep it up and publish the series if possible. One wonders how many toes it would trample on.

    Your mention NO is interesting. How does it affect Reactive Oxygen Species (ROS) as these seem to be involved in so many nasty actions such as mitochondrial and nuclear DNA damage and is a consequence of statin damage to the mevalonate pathway, reduction of the anti-oxidant CoQ10, and the anti-oxidant selenoproteins. As NO is rapidly oxidised does it have the same effect on ROS?

    Reply
    1. Dr. Malcolm Kendrick Post author

      The most reactive oxygen species is… oxygen. How much better off we would all be without that pesky oxygen in our bodies. If we could all just hold our breath for several hours each day we would all be far healthier 😉

      Reply
      1. John U

        I love that comment. Clearly oxygen is necessary for life and our body has found ways to use it to our advantage. I believe there is more to ROS and their existence than the obvious.

      2. Gary Ogden

        My understanding is that ROS play an essential role in metabolism. REDOX is called that for a reason.

      3. Maureen H

        There is a wonderful book by Nick Lane called “Oxygen: The Molecule that Made the World”. Included is a chapter on Linus Pauling and Vit C. It’s written for the layman, but still a bit of a challenge, for me anyway. But it is very thought provoking.

      4. mikecawdery

        I am particularly interested in ROS as it seems to pop up in so many conditions including cancer where seems to be associated with both the cause (adverse) and therapy (supportive of therapy).

        As NO is an anti-oxidant along with other natural anti-oxidants I wonder why the measurement of the Total Anti-oxidant Capacity (TAC) of blood is not a routine lab test.

  31. Mec Cham

    Another one from Science Daily –

    https://www.sciencedaily.com/releases/2016/03/160314101716.htm
    Potential new therapeutic target for hypertension may offer less side effects
    Posted: 14 Mar 2016 07:17 AM PDT
    The recent discovery of a molecule that rescues damaged blood vessels, yet preserves healthy vessels, could serve as a springboard for a new pharmaceutical therapy with fewer side effects for hypertension, report scientists.
    “This therapeutic pathway has huge potential for the average person, since about 30 percent of people develop hypertension or cardiovascular disease in their lifetime,” Dostmann says.

    We’ll see. Hope springs for an anti-hypertensive sans side effects, but if course runs true to form, then…!???

    Reply
  32. Mec Cham

    Science Daily are doing a great job today – here is another item from today’s input — imaging, the researchers are hot on the trail of imaging for plaques without the usual Gd (gadolinium) – hope not the same damage as that Gd can and all to often does, cause —

    https://www.sciencedaily.com/releases/2016/03/160314084815.htm
    A nanoparticle does double duty, imaging and treating atherosclerosis
    Posted: 14 Mar 2016 05:48 AM PDT
    Atherosclerosis, a disease in which plaque builds up inside arteries, is a prolific and invisible killer, but it may soon lose its ability to hide in the body. Scientists have developed a nanoparticle that mimics high-density lipoprotein. It can simultaneously light up and treat atherosclerotic plaques that clog arteries, which could someday help prevent heart attacks and strokes.
    (snip…) “The researchers targeted macrophages by decorating the nanoparticles’ surfaces with a molecule that selectively binds to macrophages. The team observed that the nanoparticles were engulfed by these white blood cells. “Then, when the macrophages ruptured, which is a sign of an unstable plaque, the cells spit out the nanoparticles, causing the MRI signal to change in a detectable fashion,” Banik says.

    Dhar says her lab is now using MRI to study how well the particles light up and treat plaques in animals, and she hopes to begin clinical trials within two years.”

    Reply
    1. Gary Ogden

      This is truly creepy. It is true that nanoparticles become engulfed by macrophages. However, macrophage enzymes are incapable of dissolving them, so they carry them to the tissues, including the brain, in a Trojan horse fashion. This is likely the cause of the greatest harm from vaccines, those which have an antigen-adsorbed aluminum adjuvant. To get a flavor of this, read Janine Roberts’ two books on the subject.

      Reply
  33. Mec Cham

    Here is a discourse from a Dr Sircus newsletter on the perils of statins – there are several participants :—

    Treat the inflammation not the cholesterol –
    Dr. Dwight Lundell, former Chief of Staff and Chief of Surgery at Banner Heart Hospital in Arizona told the world not to take statin drugs. “We physicians with all our training, knowledge and authority often acquire a rather large ego that tends to make it difficult to admit we are wrong. So, here it is. I freely admit to being wrong. As a heart surgeon with 25 years experience, having performed over 5,000 open-heart surgeries, today is my day to right the wrong with medical and scientific fact.
    His frontal attack on the field of cardiology tears apart the practice of prescribing medications to lower cholesterol and a diet that severely restricted fat intake. Doctors in this field have been continually bombarded with scientific literature, continually attending education seminars, all of which insisted heart disease resulted from the simple fact of elevated blood cholesterol. They were wrong. Unfortunately for too many people—dead wrong. (more…)
    http://drsircus.com/medicine/confessions-of-a-cardiologist-treat-the-inflammation-not-the-cholesterol/?utm

    Reply
  34. TS

    Six men have been resurfacing our road today. I made them all a cup of tea. One wanted no sugar. The other five wanted two spoons each. (I blame the parents!) We have a long way to go, eh?

    Reply
  35. smartersig

    So how do we increase NO through the diet. The usual suspect is Beetroot but my understanding is that Ruhbarb has by far the greatest NO producing qualities. If this is the case then Ruhbarb will be replacing Beetroot in my Blended smoothie.

    Reply
      1. smartersig

        Yes that certainly works I can vouch for it but I am sure I saw a connection with increased heart attacks from usage of L Arganine

      2. Mec Cham

        Hi Jack – certainly helps with mine. Have tried 16 anti-hypertensive drugs and ALL led to really horrible side effects. So, had to go the alternative route. From spikes of 227/117 down to a reasonable even beat of 150 – 160/85 – 95.
        Yes. A few years ago had a minor CVA which caused bifocal diplopia, and gradually, over time, led to loosing the central vision in my right eye (lack of oxygen/blood to the retina) – but one factor in favour, bifocal diplopia resolved ! Diplopia is a wretched condition and prism specs are a nightmare to drive in in low light…halos/refracted splintered light. Ugggg.
        So, L’Arginine to the rescue. Loathe beetroot and ditto rhubarb ! Have been taking L’Arginine for ‘n number of years. Not that diligent, and do take breaks, but it is my stand-by.

    1. Mr chris

      smartersig
      A link please about rhubarb, as opposed to beetroot which I am trying to convince myself I like.
      I adore rhubarb.

      Reply
  36. Mec Cham

    Smartersig : “I am sure I saw a connection with increased heart attacks from usage of L Arganine”
    Put in an internet search, many links, both for and against ! Extolling the virtues of : cautioning the use of…! The following is sort of middle of the road. There is a small comments section which might interest :-
    http://www.drugs.com/npc/l-arginine.html

    Reply
    1. smartersig

      Interesting that quite a few heart healthy foods are also rich in L Arganine eg nuts, oats sesame seed brown rice etc. I eat a handful of walnuts every day as part of my breakfast ritual

      Reply
  37. repsort

    Thank you for this series.

    RE: factors, that reduce EPC numbers include…

    I Figured that if Type 2 made the list, Type 1 Diabetics would likely have reduced EPC numbers.. The increased risk/occurance of CVD in the T1D community is well known..

    Sure enough. Here’s a study showing a relationship between A1C and EPC count..
    http://diabetes.diabetesjournals.org/content/53/1/195.full
    “The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA1c (R = −0.68, P = 0.01)."

    Reply

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