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A biting commentary on just who is writing treatment guidelines for diabetes and cardiovascular disease was published in the British Medical Journal, summarized in theHeart.org's HeartWire here.

"About half the experts serving on the committees that wrote national clinical guidelines for diabetes and hyperlipidemia over the past decade had potential financial conflicts of interest (COI), and about 4% had conflicts that were not disclosed.

"Five of the guidelines did not include a declaration of the panel members' conflicts of interest, but 138 of the 288 panel members (48%) reported conflicts of interest at the time of the publication of the guideline. Eight reported more than one conflict. Of those who declared conflicts, 93% reported receiving honoraria, speaker's fees, and/or other kinds of payments or stock ownership from drug manufacturers with an interest in diabetes or hyperlipidemia, and 7% reported receiving only research funding. Six panelists who declared conflicts were chairs of their committee.

"Of the 73 panelists who had a chance to declare a conflict of interest but declared none, eight had undeclared COI that the researchers identified by searching other sources. Among the 77 panel members who did not have an opportunity to publicly declare COI in the guidelines documents, four were found to have COI."

The closing quote by Dr. Edwin Gale of the UK is priceless:
"Legislation will not change the situation, for the smart money is always one step ahead. What is needed is a change of culture in which serving two masters becomes as socially unacceptable as smoking a cigarette. Until then, the drug industry will continue to model its behavior on that of its consumers, and we will continue to get the drug industry we deserve."

It's like having Kellogg's tell us what to each for breakfast, or Toyota telling us what car to drive. The sway of the drug industry is huge. Even to this day, I observe colleagues kowtow to the sexy sales rep hawking her wares. But that's the least of it. Far worse, even the "experts" who we had trusted to have objectively reviewed the evidence to help the practitioner on Main Street appears to be little more than a hired lackey for Big Pharma, hoping for that extra few hundred thousand dollars.

Although Dr. John Cannell's most recent Vitamin D Newsletter concerns the connection between autism and vitamin D, and has nothing to do with coronary plaque reversal, this fascinating discussion between a mother of an autistic boy and Dr. Cannell is so enlightening that I thought that it was still worth passing on.

I also feel very deeply for parents with autistic children, who I see struggle with the developmental difficulties their children encounter. (I even have several patients who are parents of 2 or 3 autistic children.)

As always, Dr. Cannell is at the cutting-edge of converting hard scientific information into practical use. You will note several points or questions raised:

1) Dr. Cannell advocates a powdered capsule form of vitamin D. In my experience, most powdered or tablet forms do not work. But some do. He apparently has success with the brand he specifies.

2) Are there vitamin D-receptor (VDR) genotypes that respond differently? Should there be different 25 (OH) vitamin D blood level targets for different VDR genotypes? Nobody knows yet, but it will be an important question to explore in the future.

3) Is heavy metal toxicity, at least in its milder forms, a surrogate for vitamin D deficiency? (Are chelationists unwittingly treating vitamin D deficiency?)

4) If this is a genuine association, and vitamin D replenishment exerts profound neurologic effects in autistic children, does a similar, though less marked effect, hold in non-autistic children? Will children perform better, learn more effectively, etc. with vitamin D supplementation to normal levels?

5) Vitamin A--Is vitamin A with vitamin D good or bad? This one I do not have an answer to. Reading the literature Dr. Cannell cites didn't help much. (Dr. BG--Any comments? Dr. BG is a vitamin A advocate.)

Perhaps, should the association between autism and vitamin D hold, it raises more questions than it settles. But, true to my experience with vitamin D, every day I stumble on some unique, fascinating effect, all beneficial. We continue to learn new lessons about vitamin D and Dr. Cannell's insights as a practicing psychiatrist deeply concerned with vitamin D issues have helped enormously.

(Sorry, but I did not copy the links to the literature Dr. Cannell cites. To obtain the links, go to the original Vitamin D Newsletter.)

The Vitamin D Newsletter
June 2008

This month we feature a remarkable series of letters from a mother of an autistic son who treated her child with vitamin D. It is the first case report in the medical literature suggesting vitamin D has a treatment effect in autism.

First, a brief case report and then a more detailed exchange of emails between the mother and me.

Case Report:

John is a seven-year old boy living in the northeastern U.S. with a long-standing diagnosis of autism. Symptoms include temper tantrums, repetitive self-stimulatory behavior, impaired language, mood swings, fear of being alone, toileting problems, dysbacteriosis, and impaired muscle strength. John spends a lot of time outdoors starting in the spring and his mother noticed a distinct seasonal variation in his symptoms in that he improved in the summer and regressed in the winter. A 25-hydroxy-vitamin D in April of 2008 was 25 ng/ml and obtained after John had begun to play outside. Due to the seasonality of John's symptoms the mother consulted me. I advised the mother to stop all products containing vitamin A including cod liver oil and begin John on 5,000 IU of vitamin D3 per day for two weeks followed by 2,000 IU per day in the form of powdered vitamin D dissolved in juice. Within a week of starting the vitamin D, John's language began to return and he was no longer as fearful of being alone. At the end of two weeks his language showed further improvement, he began to toilet himself, counted to 10 and knew the spelling of his name. After three weeks language continued to improve and some improvements were noted in his dysbacteriosis. After four weeks of vitamin D treatment, the mother noted improvements in muscle strength as well as continued improvements in language. A repeat 25-hydroxy-vitamin D is pending while John continues taking 2,000 IU of vitamin D per day.

Before you read the series of emails between the mother and me, I'd like to caution that this is only a case report of sorts and does not prove a treatment effect. Spontaneous remissions, while rare in autism, have been reported, thus the supplemental vitamin D may have had nothing to do with his improvement. If the response is due to vitamin D, there is no assurance it will prove lasting. I think it unlikely that older autistic children or individuals with severe autism will show these sorts of apparent improvements. Furthermore, autism is a multifactorial disease with strong genetic roots and it is highly unlikely that treatment of vitamin D deficiency in all autistic children will result in similar improvements. Finally, I did not examine this child, and I am relying on the child's mother to report both his condition and his apparent response to vitamin D treatment. However, the mother agreed to speak with the press about her son and allow for independent confirmation of the apparent treatment response.

Below are the emails, edited for brevity, clarity, and confidentiality.

Dear Dr. Cannell:

I am writing because I believe my son John is strongly affected by vitamin D and I need some advice. John is seven and autistic and weighs 50 pounds. We live in the northeastern part of the United States . He starts spending lots of time outside in May and continues until September. Every year, like clockwork, he has the same patterns of behavior and ability. After about six weeks of sun exposure, every July, he begins feeling much better, seems to be comfortable in his skin, does not have as much self-stimulatory behavior, can eat a variety of foods and has language. This past summer, he was using 14-word sentences. By the end of November, he can't even ask you for a cup of juice. He becomes more exclusive, has emotional highs and lows, has tantrums and is easily frustrated.

His 25(OH)D level on April 15th was 25 ng/ml but he had already been going out in the sun so his level must have been lower in the winter. I have had his genetics tested (Nutrigenomic) and he has mutations in his vitamin D receptors:

VDR Bsm/Taq ++
VDR Fok --
VDR Taq ++

My first question, does it sound like the changes in his behaviors and abilities could be caused by lack of vitamin D? Could you elaborate on the time it would take to get adequate amounts of vitamin D to start seeing positive results? For example, even if he starts going out in the sun in May, it's usually not until July that I see positive changes. Then would it take a month or two to go back to being deficient, thus explaining his 'regression' by the time November comes around. Secondly, I am looking at different forms of vitamin D therapy: a vitamin D lamp, vitamin D3 cream, or oral vitamin D. Can you tell me what might be the best form during the winter months?

Thank you very much for your time and attention.

Jane, Boston MA

Dear Jane:

Yes, it is possible your son's autism is related to vitamin D. Such seasonality has been reported before in autism, both in an individual and in autistic children at a summer camp. Although suggestive, such seasonality does not prove a vitamin D connection. Sun exposure, unless it is full body, takes several months to get vitamin D levels up. If sunblock or clothes are worn sun exposure will not get 25(OH)D levels much above 30 ng/ml. As far as the "mutations" you list, they are actually vitamin D receptor (VDR) polymorphisms and not referred to as mutations although all such changes occurred through mutations at some time in the past. VDR polymorphisms are simply the different structures of the vitamin D receptor that different people have and they are widely distributed. A pilot study of actual VDR receptor mutations did not detect VDR mutations in 24 autistic individuals but they did not assess for VDR polymorphisms. However, a highly significant association exists between one VDR polymorphism and larger head size. Mean head circumference is larger in autism.

Yan J, et al. Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases. Neurosci Lett 2005;380(1-2):37-41.

Handoko HY, et al. Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures. Am J Hum Biol 2006;18(3):415-7.

Lainhart JE, et al. Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. Am J Med Genet A 2006;140(21):2257-74.

Lainhart JE, et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry 1997;36(2):282-90.

I emailed the world's foremost expert on VDR polymorphisms asking him about your son's polymorphisms and his reply, quite technical, is below.

Dear John:

I apologize for the delay in getting back to you regarding VDR polymorphisms. Initial studies by Eisman and coworkers many years ago suggested that several of the polymorphs identified above in the VDR gene (Bsm/Tag) correlated strongly with osteoporosis. Despite the hoopla, subsequent analyses by many different investigators did not really confirm these results, i.e. only a very modest (3%) correlation. This spawned multiple studies searching for correlations between VDR polymorph's and cancer, autoimmune disease and so forth. It is fair to say from all of these studies that the correlation is at best weak, and in most cases non-existent. Part of this may be due to the fact that the Bsm and Taq polymorphs are located in VDR gene introns and as a first approximation cannot affect the VDR protein's function. This is not an absolute statement, however, as our work is now showing that regulatory regions that control the VDR's expression are located within introns as well as upstream. Therefore the possibility exists that these polymorphs could affect expression, although we have not found these regions to contain enhancers yet. This is clearly where gene and disease studies are going. The only polymorph that could affect function is the Fok1 site, which we identified many years ago following our initial cloning and structural analysis of the human VDR gene. The presence of this site leads to the expression of a shorter VDR protein (424 aa) that is purported to have a slight increase in transcriptional activity (10%?) vs the large protein (427 aa). The above analysis suggests that this polymorph is absent, leading to production of the larger perhaps less active protein. On a single patient basis, it is really difficult to conclude anything regarding this finding. Indeed, despite large numbers of patients, the VDR polymorph have not really revealed any significant insight. Given the summer correlations, it is probably more likely that the individual is low in vitamin D3 in winter.

Sincerely,

Professor John Doe

Thus, one of your son's polymorphisms may have less functionality but that should be easily overcome by higher vitamin D levels. The first thing to do is stop all vitamin A, multivitamins containing vitamin A, or cod liver oil and start vitamin D. As you will see below, vitamin A antagonizes the action of vitamin D and he should have plenty of vitamin A if he eats colorful vegetables, colorful fruit, eggs and fortified oatmeal. As far as vitamin D, I think the easiest way to give vitamin D is powdered capsules, not a cream. You can open the capsule and put the powder in about anything, such as juice. To buy the capsules, go toBio Tech Pharmacal and buy both a bottle of the 5,000 and the 1,000 IU capsules. He should take one 5,000 IU capsule a day for two weeks then take 2,000 IU per day. After a month, go to the doctor and have another 25-hydroxy-vitamin D blood test. Do not let your doctor order a 1,25-dihydroxy-vitamin D as it will give you and your doctor false information about your son's vitamin D status. The other option is buying a Sperti vitamin D light. Daily use of the light on both sides of his trunk will raise levels fairly quickly but he should still have a 25(OH)D blood test every month to assure his levels rise to the mid level of normal ranges, about 70 ng/ml. Vitamin D is very safe. Your son would have to take more than 10,000 IU a day for more than a year to have any risk of toxicity. If he improves and his level is 50 ng/ml, the next question is would he improve even more if his level was 70 ng/ml? Some lifeguards have levels of 80-100 ng/ml; normal ranges in the labs in the USA are 30 -100 ng/ml (ideal ranges are 50 -100 ng/ml.) If you have any more questions, let me know. I certainly want to know how he is doing.

Sincerely,

John Cannell

Dear Dr. Cannell:

It has been one week on 5,000 IUs of vitamin D3 daily and already we're getting some language back! We haven't had original language since probably around the end of November. The only language we have had in the past five months has been verbal scripting. Today John has already told me "turn off the TV" and "clean up the water". This is all very exciting. Will it last? I will continue to keep you updated on progress and change in behavior. One more thing, all winter long he was afraid to be by himself anywhere. Now he is starting to be able to be in another room or outside by himself.

Thanks so much,

Jane

Dear Jane:

I can't tell you how happy I am for you. I suspect John will continue to improve. Do you have any parent rating scales or does his treating pediatrician have any objective rating scales? If you have before and after rating scales or his treating doctor does then it becomes important to track his progress on an objective measure. Jane, if you are a member of any autism discussion groups, you should post about this, including doses used. If your son's case is typical, then hundreds of thousands of autistic children may be helped with vitamin D.

John Cannell

Dear Dr. Cannell:

It has been two weeks on 5,000 IU per day and I want to inform you that we are having continued success with language. Continued in the sense that it is consistent, it wasn't just a one day fluke. In addition, he is taking himself to the bathroom; this is another thing that goes away in winter months. I usually have to catch him holding it in and then suggest he go, but now he is going completely by himself. In therapy last week, he started drawing again. He drew a bee and then ran around the room buzzing. His toileting is consistent with his therapists, not just mommy. Last night, I asked him to count to 10 for me and he did - quite enthusiastically. Then I said what does J-O-H-N spell? It took him a bit but then he said "John."

Unfortunately, the last scale taken was when he was 3 when he had his first developmental evaluation. But we do track behavior and language on a weekly basis. The forms we fill out give a good indication as to how he is doing.

I belong to a parent forum. It was created by a doctor named Amy Yasko. She's a PhD, a researcher, not a medical doctor. It was through her that I got John's genetics tested. She advocates vitamin D as being very crucial. I will post something on her forum for the parents there. However, if the parents on the forum are following her recommendations, they should be taking it already - 2000 IUs in winter and 1000 IUs in summer is her recommendation. I will post something on the forum to really emphasize how important vitamin D is.

Jane

Dear Jane:

I'm glad the improvements are continuing. I see Dr. Yasko recommends 10,000 IU of vitamin A/day as well as cod liver oil. I strongly disagree. Make sure your son is taking neither vitamin A nor cod liver oil. Rather, make sure he eats colored fruits and vegetables as well as fortified oatmeal. Vitamin A interferes with vitamin D's function, especially at the doses Dr. Yasko recommends.

Vitamin A antagonizes the action of vitamin D. In humans, even the vitamin A in a single serving of liver impairs vitamin D’s rapid intestinal calcium response. Furthermore, the consumption of preformed retinols, even in amounts consumed by many Americans in both multivitamins and cod liver oil appears to be causing low-grade, but widespread, bone toxicity, perhaps through its antagonism of vitamin D. In a recent dietary intake study, Kyungwon et al found high retinol intake completely thwarted vitamin D’s otherwise protective effect on distal colorectal adenoma and they found a clear relationship between vitamin D and vitamin A intakes as the women in the highest quintile of vitamin D intake also ingested almost 10,000 IU of retinols/day. As early as 1933, Hess et al warned about vitamin A consumption, concluding, “as to a requirement of thousands of units of vitamin A daily, the unquestionable answer is that this constitutes therapeutic absurdity, which, happily, will prove to be only a passing fad.”

Rohde CM, Deluca HF. All-trans retinoic acid antagonizes the action of calciferol and its active metabolite, 1,25-dihydroxycholecalciferol, in rats. J Nutr. 2005;135(7):1647-1652.

Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res. 2001;16(10):1899-1905.

Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;83(2):191-201.

Oh K, Willett WC, Wu K, Fuchs CS, Giovannucci EL. Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women. Am J Epidemiol. 2007;165(10):1178-1186.

Hess AF, Lewis JM, Barenberg LH. Does our dietary require vitamin A supplement? JAMA. 1933;101:657-663.

Unfortunately, Hess’s prophecy of a passing fad proved premature and many Americans continue to consume “absurd” and dangerous quantities of vitamin A. For example, multivitamins, until recently, had small amounts of vitamin D (200 to 400 IU) but high amounts of preformed retinols (5,000 to 10,000 IU). This pales in comparison to a tablespoon of modern cod liver oil, which contains sub-physiological amounts of vitamin D (400 to 1200 IU) but supra-physiological amounts of completely preformed retinols (5,000 to 15,000 IU or in some cases 30,000 IU).

John Cannell

Dear Dr. Cannell:

It has been three weeks and he went from 5,000 IU of vitamin D per day to 2,000 IU per day a week ago. His language is increasing. He's now back to saying the things he wants with some prompting. He also has gut dysbiosis and I'm sure the D is helping with microbes in his gut. He has a lot of problems with his immune system and bacteria and viruses. Also, doesn't vitamin D aid in the production of glutathione? I feel that could be a big part of his increased language.

Jane

Dear Jane:

Yes, abnormal immune responses are associated with both autism and vitamin D deficiency. For example, autistic individuals have immune abnormalities that show a striking similarity to the immune functions affected by vitamin D. Animal evidence indicates some vitamin D deficiency induced brain damage may be malleable, that is, vitamin D may partially reverse the brain damage, if given early enough. These studies offer hope that sunlight or oral vitamin D, especially in young autistic children, may have a treatment effect.

Ashwood P, et al. The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006;80(1):1-15.

Cantorna MT, et al. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004;80(6 Suppl):1717S-20S.

Burne TH, et al. Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle. Physiol Behav 2004;81(4):651-5.

Both the brain and the blood of autistic individuals show evidence of ongoing chronic inflammation and oxidative stress. That is, the disease process is probably increasingly destructive. Further hope for a treatment effect rests in activated vitamin D's powerful anti-inflammatory properties. Its administration reduces production of inflammatory cytokines in the brain, which have consistently been associated with cognitive impairment. Furthermore, activated vitamin D is remarkably neuroprotective by stimulating neurotropin release, reducing toxic cellular calcium levels in the brain, inhibiting the production of nitrous oxide, and by its immunomodulating properties, especially in reducing inflammatory cytokines and by increasing brain glutathione.

Moore ME, Piazza A, McCartney Y, Lynch MA. Evidence that vitamin D3 reverses age-related inflammatory changes in the rat hippocampus. Biochem Soc Trans 2005;33(Pt 4):573-7.

Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A. Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels. Nephrol Dial Transplant 2006;21(4):889-97

Kalueff AV, Eremin KO, Tuohimaa P. Mechanisms of neuroprotective action of vitamin d(3). Biochemistry (Mosc) 2004;69(7):738-41.

This last function of vitamin D, increasing cellular levels of glutathione, may explain the purported link between heavy metals, oxidative stress, and autism. For example, activated vitamin D reduces iron-induced and zinc-induced oxidative injuries in rat brain. The primary route for the neurotoxicity of most heavy metals is through depletion of glutathione and subsequent generation of reactive oxygen and nitrogen species. Besides its function as a master antioxidant, glutathione acts as a chelating (binding) agent to remove heavy metals. Several studies indicate autistic individuals have difficulty excreting heavy metals, especially mercury. If vitamin D deficient brains are unable to utilize glutathione properly, and thus unable to remove heavy metals, they may be oxidatively damaged by heavy metal loads normal children easily excrete. The amount of activated vitamin D in the brain directly depends on how much vitamin D is made in the skin or put in the mouth.

Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002;13(3):100-5.

Chen KB, Lin AM, Chiu TH. Systemic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain. Ann N Y Acad Sci 2003;993:313-24.

Lin AM, Chen KB, Chao PL. Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS. Ann N Y Acad Sci 2005;1053:319-29.

Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12(10):1161-208

Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J Toxicol Environ Health B Crit Rev 2006;9(6):485-99.

Sincerely,

John Cannell

Dear Dr. Cannell:

It has been a month now and John's Improvements are continuing. In the last week, he has been using his muscles more, he goes on the swing outside and lifts his legs and bends in ways that take core muscle strength. This is yet another skill or interest that left and is returning. I will report more next week.
Jane

Conclusion:

It is too early to say vitamin D has a treatment effect in autism. However, a simple risk/benefit analysis suggests that autistic children should be diagnosed and aggressively treated for vitamin D deficiency. If readers want to learn more about vitamin D and autism, they can obtain the entire paper on the link below. Unfortunately, Elsevier charges $31.50 to download it. You can read a similar document for free on the website, where we first published the theory a year ago.

Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-9.

http://vitamindcouncil.org/newsletter/2007-may.shtml

In summation, autistic children should be given enough vitamin D to get their 25(OH)D levels up to the mid to high range of normals, that is, 70 ng/ml (175 nmol/L in countries that use the metric system). In the absence of sun exposure, this usually requires long-term administration of about 1,000 IU/day per 20 pounds of body weight with a loading dose of 2,000 IU of vitamin D/day for every 20 pounds of body weight for the first two weeks. As individual variation in response is very high, they should have 25(OH)D blood tests every month until their level has stabilized around 70 ng/ml. They should stop all products containing preformed retinols (vitamin A), especially cod liver oil.

John Cannell, MD
The Vitamin D Council

This is a periodic newsletter from the Vitamin D Council, a non-profit trying to end the epidemic of vitamin D deficiency. If you don't want to get the newsletter, please hit reply and let us know. As we are a 501(3)(c) non-profit corporation, dedicated to ending vitamin D deficiency and not making money, the Vitamin D Council does not copyright this newsletter. Please reproduce it and post it on Internet sites. If this newsletter proves useful to a child you know with autism, the Vitamin D Council asks for a donation as we have not been able to secure a grant and our bank account balance is again below $5,000. Send your tax-deductible contributions to:

The Vitamin D Council
9100 San Gregorio Road
Atascadero, CA 93422

Jim Purdy
10/14/2011 1:36:03 AM |

I am not a fan of any drugs, and as a result, I change primary care physician regularly, usually after two visits.
ON THE FIRST VISIT, I explain to the new doctor that I do not, and will not, take prescription medications. I explain that the only reason I am in their office is to get orders for lab work, so that I can review the results and make my own decisions about lifestyle changes, especially diet. The doctor then calls me" non-compliant" and prints numerous computer-generated prescriptions anyway. Obviously, it is the doctor who is non-compliant, since I have already said I do not want drugs.
ON THE SECOND VISIT, the doctor asks, "Have you been taking your medications as ordered?" When I tell the doctor again, as I did at the first visit, that I do not take medications, the doctor says, "You're crazy and suicidal." I then find the next doctor, and the cycle starts over.
As I see things, I have two choices when I feel ill:
1. I could attack my body with some bizarre BigPharma chemicals that our ancestors' bodies have never dealt with in millions of years of evolution (Oxycodone, hydrocodone? Really? Are doctors nuts?).
2. Or I could get out of the way and let my body heal itself as has been done over many millions of years of evolution. All I want to do is support that process by making sure to give my body the proper nutrition in the form of the appropriate whole foods.

Dr. William Davis
10/14/2011 3:40:23 AM |

Wow, Jim. Creepy.

Don't despair: I'm confident that you will eventually find a healthcare practitioner who will act as your advocate, not a provider of drugs. It may take, unfortunately, going through quite a few practitioners before you come on such a person.

Suze
10/19/2011 1:44:46 AM |

Great post. I am starting to think there are two kinds of people - those who seek drugs and those who run from them. LOL.
Among other occupations, I am an OR nurse. I have been wined and dined by the best reps ever, to buy their wares for surgery. It's all about the money.The drug companies have a lot to lose if we all quit taking their meds. Which is exactly what I want to do. I do not want to be a slave to a diagnosis and accompanying pill bottle. I want to be freeeeee.
This is not to say there is a time and place for medicine. There IS. But not for every sniffle.

Jeanne
10/20/2011 11:44:20 AM |

Boy Suze, I can relate! I'm a nurse as well and spent lots of years in NICU, but a change to chemical dependancy/psych was eye opening and downright disgusting in the amount of meds handed out.

I used to ask patients if they were hungry when dispensing a 6oz. Cup FULL of various pills before breakfast!
Couldn't take it and quit. Couldn't be a party to pharm management over real therapy. I also take as few pills as possible, especially antibiotics.

N
11/30/2011 6:36:01 PM |

Hi Doc,

I just visited my parents, and my mom shared her recent blood work with me.
Her cholesterol was a mere 210, and her doc (general practitioner), put her on a statin !!!
I told her about your blog a bit and particle size, but of course she's hesitant since her doctor obviously has more credibility than me.

Outside of eating better, what next steps should I advise her to take? She agreed to request a cholesterol particle size test (is there an official name for this?).

Dr. William Davis
12/1/2011 4:22:01 AM |

Yes, N: Lipoprotein testing, such as NMR Lipoprofile or Atherotech VAP.

It really shouldn't be that tough, but we are battling the incredible ignorance in the primary care community who is spread too thin to master any one area.

concerned heart
6/1/2008 4:30:00 PM |

Vitamin D3 is wonderful vitamin, but it won't change the brain defects in severe autism.

One cause of non-familial autism is an older father at conception that results in mutations in sperm DNA and possible autism, schizophrenia, cancers, birth defects etc. etc. People need to be informed about the male biological clock. Of course in familial autism, schizophrenia, Alheimer's, cancers, the mutations happened in earlier generations.

http://www.telegraph.co.uk/news/uknews/2059130/Scientists-reveal-dangers-of--older-fathers.html

http://how-old-is-too-old.blogspot.com/

Dr. B G
6/1/2008 5:12:00 PM |

Like you, I believe we need to 'eat food'. Whole, balanced, high quality food provides all that our bodies require. (And supplements fill in when these requirements cannot be met.)

Perhaps Cannell is aware of an interaction betw these VDR polymorphisms and excessive doses of pre-formed retinol? I agree with Cannell that high doses of Vitamin A (which can be accumulated due its fat-soluble nature) can antagonize and create the same problems Vit A is supposed to prevent/tx: osteoporosis, proliferation, inflammation, etc (much like vitamin D toxicity). BTW New formulations of cod liver oil have 75% less vit A now. Chris Masterjohn has tried to address the vit A and vit D conflict.
http://www.greenpasture.org/content/VitaminA.pdf

What is autism? Is it sign of many deficiencies and environmental interactions (both maternal and neonatal/pedi)??
1) in utero effects from maternal conditions (maternal low steroid/chol diet, low EPA/DHA diet, vitamin D hypovitaminosis low vit A diet)?
2) neonatal/pediatric vit D hypovitaminosis? (which can lead to Pb++/lead nonselective uptake?)
3) wheat exposure and silent celiac dz (and subsequently deficient immunity which can lead to fungal/eukaryotic/yeast infxns)?

Stocker CJ, et al. Fetal origins of insulin resistance and obesity.
Proc Nutr Soc. 2005 May;64(2):143-51. PMID: 15960859

Antipatis C, et al. Moderate maternal vitamin A deficiency affects perinatal organ growth and development in rats. Br J Nutr. 2000 Jul;84(1):125-32. PMID: 10961169

Morris GS, et al.Maternal consumption of a low vitamin D diet retards metabolic and contractile development in the neonatal rat heart. J Mol Cell Cardiol. 1995 Jun;27(6):1245-50. PMID: 8531206

Gallagher EA, et al. The effect of low protein diet in pregnancy on the development of brain metabolism in rat offspring.
J Physiol. 2005 Oct 15;568(Pt 2):553-8. PMID: 16081486

-G

Richard A.
6/1/2008 8:11:00 PM |

DHA from fish oil might be beneficial for Autism also. Carlson's Super-DHA contains 500mg of DHA per normal sized softgel. Jarrow's Max DHA contains 250mg of DHA per smaller sized softgel.

Anonymous
6/1/2008 10:47:00 PM |

"5) Vitamin A--Is vitamin D with vitamin D good or bad?"

I'm sure you meant so say: Is vitamin A with vitamin D good or bad?

Lynn

Dr. William Davis
6/1/2008 11:44:00 PM |

Thanks, Lynn.

Stephan
6/2/2008 8:08:00 PM |

I have a VERY hard time believing that preformed vitamin A in the amounts found in liver/cod liver oil are unhealthy.

Our hunter-gatherer ancestors almost certainly prized liver, as do modern HG groups.  Weston Price identified a high intake of vitamin A as one of the characteristics of traditional cultures that have excellent bone and dental health.  That indicates good mineral metabolism.  With empirical evidence like that, it's hard to take seriously predictions based on molecular arguments and weak epidemiological associations.

What I might be willing to believe is that vitamin A is harmful in the presence of vitamin D deficiency.  All the cultures Price studied presumably got plenty of vitamin D from sunlight.

It makes no sense that vitamin A would seriously interfere with vitamin D function, considering our ancestors have been getting plenty of both for the last million years or more.

Jessica
6/2/2008 9:07:00 PM |

"Dr. Cannell advocates a powdered capsule form of vitamin D. In my experience, most powdered or tablet forms do not work. But some do. He apparently has success with the brand he specifies."

Myself, my dad, my physician, and our patients (thousands of them) have had much success using the 5,000 IU tablets from Bio-Pharm as Dr. Cannell mentioned. We've seen significant increases in 25-OH levels from the tablet form.

Dr. B G
6/3/2008 3:50:00 AM |

Dr. Davis,
I believe Cannell uses the powdered capsules as a convenient dosage form for children to be sprinkled on to food. (I think?)

Stephan -- I totally agree!  Could Cannell have come up with incorrect conclusions from confounding data?

The only time I found antagonism between vitamin A and vitamin D is in the situation of vitamin D deficiency (as you said) -- and each of the examples Cannell lists are such cases (all the animals, all the men and the women  -- for the humans, I assumed because frequently reported EVERYONE in the world has 25(OH)D < 55-60 ng/ml below the  TYP goal/normal).

This is the only explanation I could come up with (because otherwise it doesn't make sense, right? to me or my nutritionist who consumes Blue Ice highly distilled cod liver oil daily).

In the trials Cannell lists, I would assume that vitamin D deficiency is the baseline case (in the colorectal trial, vit D intake > or < 400 IU/d was studied -- and we all are aware that is woefully inadequate, by a magnitude of TEN).  Also, for the in vitro studies, all the animals were first UVB deprived then fed only vitamin D-depleted and retinol-depleted diets, and therefore all the VDRs (vitamin D receptors) and vitamin A receptors were nonexistent/downregulated.  For humans, 6-8wks are required for vit D benefits to be exerted via supplementation, and the experiments did not provide enough time for that.  The experimental conditions were extreme... Yet probably mirrors the general population -- sun-deprived and excessively vitamin D depleted (again not individuals who follow TYP!).

Evolutionary-wise, humans had abundant sun (vitamin D), abundant movement and abundant vitamin A-rich foods.  When abundant vitamins A and D are together, toxicity of either one does not appear to occur... neither in the literature nor reality (that I have found). I have looked hard for it.  What I found was that high dose vitamin A and D are used to treat cancers to reduce proliferation and inflammation -- prostate, breast and colon at several oncology centers in the U.S.

Just as there are antagonism petri dish trials, there are in vitro SYNERGISM trials for vitamin A and D where 'normal' cells were used which were not depleted of vitamins A and D prior to experimentation (see the 'Astaxanthin' post).  The UL (upper limit) of Vitamin A is 10,000 IU/d -- from diet and supplements. I think this is great 'dose' for any age adult provided they have adequate vitamin D repletion... with 25(OH)D3 ~60 ng/ml. I think the context of Vitamin D status and degree of repletion needs to be always addressed when looking at a vitamin A trial.  It is like many things in the human body -- all interconnected and inter-related. (or like life?)

Here, in the DeLuca article that Cannell cites... the researchers in fact found with HIGH DOSE ergocalciferol and HIGH DOSE cholecalciferol, NO ANTAGONISM with either Retinyl Palmitate OR all-trans-retinoic-acid occurred. Funny...?

I wonder why this did not make the abstract?? (perhaps this is what happens when DeLuca --the 'Godfather' of Vitamin D -- works for a drug company?  *wink wink*).
http://jn.nutrition.org/cgi/content/full/135/7/1647

TABLE 2 Retinyl acetate does not antagonize higher amounts of ergocalciferol in rats (Expt. 1)1

TABLE 6 ATRA does not antagonize higher amounts of 1,25(OH)2D3 in rats (Expt. 3)1

We have seen in the past other antagonistic things can happen with 'good' nutritional factors in the context of vitamin D deficiency:
--calcium supplementation -- leads to more coronary plaque growth

I find Cannell's thoughts on this similar to the people who 'damned' estrogen for women. In the WHI trial, when Estrogen was given to women 15-20 years AFTER menopause -- after all the ERs (estrogen receptors) had disappeared -- estrogen caused more strokes, heart attacks and breast CA. However, when estrogen was provided during perimenopause (when the ERs were still in place and intact and functional), benefits were seen like vascular integrity maintained, heart protection, MI/stroke prevention, and even breast cancer prevention. (And as you can imagine, estrogen has a role in TYP!)

-G

Rita.
6/3/2008 12:31:00 PM |

Dr. Mary Megson treats autism with cod liver oil and believes it is the natural (non-synthetic) vitamin A that is primarily responsible. She also does a ton of other stuff with the kids, as do most doctors treating this terrible epidemic.

Dr Natasha Campbell McBride works on the gut dysbiosis in autistim which causes malabsorbtion of nutrients leading to deficiencies of vitamins and minerals and also accumulation of toxins. Her book, "Gut and Psychology Syndrome" advocates the use of the Specific Carbohydrate Diet. She cured her own son's autism.

Dr. William Davis
6/3/2008 10:31:00 PM |

Dr BG--

Fascinating arguments.

I'm beginning to see the logic of your enthusiasm for vitamin A--provided vitamin D is first normalized.

Dr. B G
6/4/2008 4:29:00 AM |

Dr. Davis,

It was your 'enthusiasm' for Vitamin D that lead me to TYP...

And now my asthma (and future health and that of my family) are assuredly as protected as can be. Thank you for all that you do!

Kindly, Dr. 'G'

Gyan
6/4/2008 7:07:00 AM |

Chris Masterjohn's articles on Weston Price site also mention vitamin K2 and its role in preventing vitamin D toxicity.
He claims that vitamin D toxicty is nothing more than a vitamin K2 deficiency,
Is it plausible?. Do we need yet another vitamin?

Stephan
6/4/2008 4:55:00 PM |

Dr BG,

Thanks, that was very informative.

Linda
10/30/2011 4:00:13 PM |

What do you consider to be ideal cholesterol readings? I am about to visit a new doctor, a D.O., and I am sure she is going to insist on blood tests for cholesterol plus stress testing, etc. My thyroid TSH was 2.70, but she is already showing reluctance to prescribe any thyroid meds. It is going to be a battle.

John Lorscheider
10/30/2011 4:32:57 PM |

And it is not just about the wheat either. Itâ€™s all carbs. Fructose, oats, rice, pasta, potatoes and certain fruits, etc. all drive up HbA1c and small LDL. Just for a reality check I bought a can of and made a bowl of â€œproperly preparedâ€ Scottish oatmeal yesterday according to Nourishing Traditions. Those are the minimally processed chewy steel cut oats soaked with warm water and kefir overnight and served with butter and cream. Yeah, they were good alright, but my fasting BG was 88 and one-hour PP was 158. A fast 5-mile run and it was back down to 84. The container is in the garbage can now. This morning was two pasture raised eggs and bacon with Â½ cup of blueberries and Greek yogurt. Fasting BG 89 and one-hour PP was 88. My HbA1c went from 5.8 to 5.1 in less than a year and hope to get below 5.0 soon. The stubborn small LDL percentage dropped during same time period but still have a way to go in that regard.

Buddy
10/30/2011 8:12:20 PM |

I'm not completely sold on HbA1C < 6.0% being a useful metric for anything but populations.  The problem is that the current HbA1C tests do not control for erythrocyte age and I see wide variations among piers on simialr  grain free lowish carb healthy diets.

There has been much more research on this effect as it pertains to diabetics that have falsely low HbA1c:  http://www.ncbi.nlm.nih.gov/pubmed/9773739
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581997/

There is some evidence out there that it works the other way as well, and it makes intuitive sense that the lower inflammation and oxidation associated  with a healthy diet would increase erythrocyte longevity.

Of course observational studies about any topic (small LDL or HbA1c) are always to be taken with a grain of salt.

Rosanne
10/30/2011 8:30:42 PM |

I wonder if you have ever experienced with any of you patients  what is going on with my husband?  He has very few small LDL particles, at least according to a VAP test - he is type A with lots of large, fluffy LDL.  But his HbA1c is 6.1.  His fasting glucose is 80, 1 hour post-prandial it's 1685, triglycerides are 60.  This is all on a grain-free, very low-carb Paleo diet.  Do you have any clue what is causing the HbA1c to be elevated?  Could it be anything besides carbs?  He gets lots of exercise and is very fit and lean.

Some have suggested that too much protein can also cause elevated HbA1c, due to gluconeogenisis causing higher levels of glucose.  But why would the body make more glucose than it needs?  And why would that excess glucose not show up in his fasting and post-prandial glucose numbers?

Is there any other factor, besides blood glucose, that can contribute to elevated HbA1c?  No doctor yet has been able to answer this question for us.

Rosanne
10/30/2011 8:32:55 PM |

Sorry for the typo, his 1 hour post-prandial glucose is 85.

Dr. William Davis
10/30/2011 9:08:02 PM |

The most common explanation, Rosanne, is that the HbA1c can stay high long after blood sugars have come under control.

It may be due to the extended longevity of RBCs that occurs in the setting of low-carbohydrate diets that allow a previously high HbA1c to stay high for an extended period.

There's also the possibility of a hemoglobin variant that allows this.

I would put more stock in the blood glucose values by fingerstick than the HbA1c.

arlene
10/31/2011 12:42:56 AM |

Thank you for explaining this. I just had my blood work done for the first time since quitting wheat and going low carb in April. Since I've lost a lot of weight, and a lot on my waist, I am very curious to see what my numbers are. This will help me compare the important stats. What is an ideal HbA1c?

pjnoir
10/31/2011 7:37:40 PM |

I can't go near oatmeal, steel cut or any other type. Its just eggs and avocados for breakfast these days with a lot of Asparagus in the spring with my yolks. Oatmeal has been banished for good.

Bob Sparkes
10/31/2011 10:46:27 PM |

Your article discuses how the combination of small LDL particles and high blood sugar
results in plaque. Is the article cited below by University of Washington at St. Louis useful here? The article points out the role of low Vitamin D in plaque formation with LDL and high blood sugar. Or am I confusing two separate mechanisms in plaque formation.

http://news.wustl.edu/news/Pages/14489.aspx

Dr. William Davis
11/1/2011 2:01:29 AM |

Hi, Bob--

Yes, I believe it is two unrelated mechanisms. However, this is a fascinating finding to tell us why people do so well from a heart standpoint when we correct vitamin D deficiency.

Dr. William Davis
11/1/2011 2:01:45 AM |

Smart move, Pj!

Dr. William Davis
11/1/2011 2:03:57 AM |

Hi, Arlene--

We aim for 5.0% or less.

learn chinese
11/1/2011 4:05:55 AM |

Thank you for explaining the topic. i learn more about Small LDL. great post.

Jeanne
11/1/2011 5:36:29 AM |

Dr. D,
Can this be related to the lysine- arginine balance in the body? Would taking arginine supplements affect the amount of lysine residue causing problems in any way? Just thinking out loud ...

Thanks!

Jeanne

Amit
11/1/2011 8:01:31 AM |

HI Doctor Davis,

I know its not the right place, but I could not find your email.

I read "wheat belly", it was revolutionary for me, and I am persuaded it can bring much relieve to many ailments.

I also wrote several posts about this issue on my health blog (in Hebrew) based on your book and your Blog.

Thank you for the great service you are offering in your work!

Amit.
Israel.

Janis
11/1/2011 2:40:01 PM |

Hello Dr. Davis,
I'm new to your blog. Just finished reading Wheat Belly. Excellent book! I also listened to the podcast with Robb Wolf. That's how I heard about you. Not to get off topic (didn't know how else to contact you) and this is probably a silly question, but would like clarification if you could help. I've been purchasing the 85% Lindt chocolate bars until you mentioned that you eat the 90%. I read the label and it said that it is pressed with alkali. You mentioned to avoid this process as it removes the healthful flavonoids. By saying "pressed" is that a different process? The chocolate was very good, but I want to make sure I'm getting the healthful flavonoids, especially when we don't eat too many sweets. Thank you so much for your time.

Might-o'chondri-AL
11/1/2011 6:44:50 PM |

Hi Dr.,
I am confused how to reconcile HbA1c details from J Am Coll Nutrition 2005, Vol.24(1):22-29
"Dietary Carbohydrate and Glycated Protein in the Blood in Non-Diabetic Subjects"
http://www.jacn.org/content/24/1/22.full
(and their relevant references no. 10 - 19 & 34-39 )

Rosanne
11/1/2011 7:15:17 PM |

This has been going on for 2 1/2 years and in fact, the longer he has been low-carb Paleo, the higher the HbA1c has gotten. When he started, it was 5.5 and has slowly
crept up to the 6.1 reading.
Thanks for the mention of the hemoglobin variant, I guess that's must be it. Can we stop worrying about the HbA1c since his glucose values are so good?

STG
11/1/2011 7:34:13 PM |

Dr. Davis:
What do you you think of Jenny Ruhl's advocacy of the 5% club at Blood Sugar 101? Your guidelines appear to be more aligned with Dr. Bernstein's and Dr. Ron Rosedale's? Do you think that all individuals ( including prediabetics, daibetics and glucose intolerant ) should strive for a HbA1c below 5%?

Dr. William Davis
11/2/2011 1:36:45 AM |

HI, STG--

That is precisely what I aim for, also: HbA1c of 5.0% or less. At that level, metabolic consequences of blood sugar essentially disappear. This is, of course, at variance with conventional guidelines.

Dr. William Davis
11/2/2011 1:37:19 AM |

That would be my vote. Ask your doctor, also, about fructosamine, another sugar markers.

Dr. William Davis
11/2/2011 1:39:24 AM |

Hi, Might--

Were you referring to their conclusion about polyunsaturates?

Dr. William Davis
11/2/2011 1:42:08 AM |

My bar says "processed" so, yes, the flavonoid content can be expected to be reduced in this bar. The best way to get a full dose of cocoa flavonoids is in undutched cocoa powder.

I still think you can enjoy your dark chocolate, but you just might not expect full benefit from this particular bar.

Dr. William Davis
11/2/2011 1:44:08 AM |

Thank you, Amit!

What is the wheat situation in Israel? Is it pushed there as much as it is here by official agencies and food companies?

Dr. William Davis
11/2/2011 1:44:43 AM |

Sorry, Jeanne, I don't believe the answer is known.

Might-o'chondri-AL
11/2/2011 3:35:43 AM |

Hi Dr. D.,
Authors in this report say glycated protein & HbA1c do not interact  with blood glucose in same way (ref #17) and that it is glycated albumen rather than glycated hemoglobin that is very senstitve to blood glucose levels (ref # 18,19); especially since 60% HgA1c is genetic (ref #61).
AGE (advance glycation endproducts) they say is more indicated by fructosamine level from high blood glucose. Although diabetics with high fructosamine also have high HbA1c. whereas for a non-diabetic  high fructosamine does not relate to their HbA1c level (ref#16).
This impies that (since most obese individuals never will become diabetic &  longevity/cognitive function of the overweight is good) a lot of the risk factor of small LDL with HbA1c depends on genetics/ epigenetics.
My confusion is if your insistence on HbA1c for non-diabetics is misdirected or just due to it being a common first test people can do.

Amit
11/2/2011 5:15:45 AM |

Wheat is the most common carbohydrate in Israel. It is eaten almost every meal. I think that the largest source of calories is wheat.

Regarding Diabetes there is no awareness that whole wheat is especially bad for such patients. Diabetes association (and many more) do recommend whole wheat. Although they are suggesting to avoid eating large quantity of bread at once.

Wheat is being pushed, though, I don't think that somebody here is pushing wheat deliberately, just coping recommendation from abroad, and using the most cheap and easy carbohydrate.

Amit.

Nora
11/2/2011 12:10:50 PM |

I have been on my Wheat Bellies journey for 8 weeks now. I am trying to follow your suggestions on heart health and I know that you have your plate full right now, but just a request. Have you ever thought of doing healthy heart retreats? I would love to have a chance to go away for a long weekend, have all my blood work done right, have it evaluated, talk to a doctor and then maybe have a few cooking classes. Throw in a few yoga classes or walks for stress reduction and you have a whole picture!!

I have high blood pressure that is 'controlled' to some degree with Tekturna (150mg) and Amlodipine (10mg). This morning it was 150/90, so it is often not very controlled. Since 9/1 and going wheat free, I have lost 23 pounds but still have 50 to lose. My take away from your writings is that plaque is the main cause of heart disease and that keeping a low blood glucose level is the best strategy, but there is not much about high blood pressure in your work. What role does it play and will being a wheat free low carber offer me relief from my high blood pressure? Or will it stay high since I have a family history of high blood pressure and therefore will probably have to continue on my meds. While I, of course, am doing everything in my power to lower my blood pressure, is it not really a number I should focus on when trying to control my heart health?

Renfrew
11/2/2011 9:08:47 PM |

Hi Doc,
have you seen this? You are prominently featured here:
http://www.lef.org/news/LefDailyNews.htm?NewsID=11842&Section=Nutrition
Great summary!

marta
11/4/2011 9:48:08 AM |

Are you going to translate his books into Spanish some day?
I'm very interested in reading them. thanks

Dr. William Davis
11/4/2011 12:48:56 PM |

Hi, Marta--

There has been interest specifically in Wheat Belly for translations. Spanish is at the top of the list.

When that happens, I will announce here and elsewhere. Thanks for asking.

Dr. William Davis
11/4/2011 12:50:33 PM |

Thanks, Renfrew!

Life Extension has been an important supporter of my efforts and vice versa.

Dr. William Davis
11/4/2011 12:53:43 PM |

Hi, Nora--

Excellent suggestion on the heart health retreats. I've thought a lot about it and will likely do it in future. Just not quite sure about the details. One hurdle: Few people want to fly to Milwaukee, so we'd have to find an exotic or interesting, probably warm, place to do it.

Hypertension is indeed a big issue. It is also among the last things to respond to weight loss and diet, often lagging behind many months after weight loss. So it really pays to be patient while you are on this health journey. Given your family history, you still might be left with hypertension, but at least you will have minimized it.

Dr. William Davis
11/4/2011 12:54:43 PM |

Thanks, Amit.

By the way, all anyone has to do is check a fingerstick blood sugar 1-hour after consuming anything wheat to observe the astounding blood sugar consequences of wheat consumption.

Dr. William Davis
11/4/2011 12:58:54 PM |

Hmmm. I'm sorry if I'm being dense, Might, but I'm still not sure I follow.

I'm not actually advocating anything except to show how glycated small LDL is a really bad player. When viewed from multiple different directions, small LDL particles are looking worse and worse. In this instance, having any measure of glycation phenomena, whether fructosamine, glycated albumin, or glycated hemoglobin, suggests that small LDL particles are also being glycated and thereby gaining heightened atherogenic potential.

Sally
11/4/2011 2:02:44 PM |

Dear Dr. Davis,

I am reading your book Wheat Belly and want to thank you so much for writing this book.

I've avoided gluten for years.  Arthritis and other annoying symptoms vanished...but I started gaining weight!   My blood sugar starting rising!   I couldn't understand it!  It was horrifying!  Well thanks to you, I realize that gluten free breads, candies, flours,  frozen pizzas, pastas and those gluten free "tv dinners" sold at Whole Foods did nothing to help my waist line or blood sugar.  I am now following the wonderfully easy plan in your book and am confident the weight will come off.

Thank you for such terrific recipes.  Will you be writing an accompanying Wheat Belly cookbook as well?  I certainly hope so.  Please do!   If not, can you recommend some cookbooks that comply with your eating instructions?

Thanks again for such a life changing book.  Sally

HS4
11/4/2011 9:09:05 PM |

There are a few people in Israel trying to enlighten others about the dangers of wheat and other 'modern' carbs. My sister is one of them, has been trying to think of ways to get some essays to the public. But what Amit says is correct - a lot of wheat is eaten there, many people buy small breads rolls daily - it's very fresh, delicious, so it will be a tough thing to stop. Many of the best restaurants in Israel serve Arabic food which always comes with freshly baked loaves of pita. The 'national snack' is pita stuffed with falafel (fried balls of ground chickpeas, onions, garlic and spices), fresh & pickled vegetablesj, hummus and/or tehina sauce. This is available everywhere and always fresh. Becasue the food is generally very good in Israel and also very fresh it's hard to avoid wheat, which I've noticed every time I visit.

palo
11/5/2011 5:07:43 PM |

Dr. Davis, the evidence speaks for itself that consumption of carbohydrates, increase small LDL, suggesting an LC diet of less than 50 grams to mitigate the damage.
But what about endurance athletes (runners, cyclists, triathletes etc.) that work out one and a half to three hours per day and consume copious amounts of carbohydrate to fuel their long workouts.
Is the exercise neutralizing the carbohydrates' harmful effects? If so, can you suggest a dosage for certain amount of exercise?

Might-o'chondri-AL
11/6/2011 8:26:57 PM |

Hi Dr. Davis,
Non-diabetics just seem to have one feature going for them - their platelets don't respond the same as diabetics. I am inclined to think that albumin in our blood is more relevant than the hemoglobin being glycated . (This is not to criticize your preventative approach , since Type II diabetes can go on to develop & I like what you are teaching us about small LDL.)

" One common qualitative change in plasma albumin is nonenzymatic glycosylation, which occurs during states of prolonged hyperglycemia....Platelet aggregation ...is enhanced in the presence of albumin that has been incubated in a medium containing levels of glucose that are higher than would be seen in normal patients but are consistent with those seen in diabetics....(Journal of Parenteral and Enteral Nutrition 18:516-520, 1994)

Once the glycation of albumin fosters more platelet aggregation in diabetics (& the insulin resistant person!) their platelets show more secretion and adhesion leading to the vascular plaque build up that the insidious small LDL can get into. Yet, for the non-diabetic the +/- 570 insulin receptors on each platelet normally respond differently to their insulin exposure.

Specifically (in non-diabetics) the insulin actually stymies the platelet from becoming "activated" and probably explains how it is that not everyone who eats carbohydrates suffers cardio-vascular insults. Of course there are non-diabetics with genetic variants that adversely affect their plaque dynamics (ex: defect in insulin receptor signalling, that receptor's Beta subunit, G-protein pathways).

( For the techno-nerds: proper insulin receptor response on platelet keeps platelet cAMP level from dropping & so no endoplasmic reticulum calcium floods out into platelet cell cytosol, platelet granule doesn't secrete ATP, platelet alpha-granule doesn't secrete P-selectin & there isn't mitogen-activated signalling to make thromboxane A2 , etc. Basically, in the diabetic/insulin resistant these processes go forward uninhibited by normal insulin signalling & their circulating platelets don't keep rolling along suspended in the bloodstream .)

Adam
11/7/2011 5:27:55 PM |

Omega 3 Fish Oil BAD NEWS for Apoe 4/3!!!

Ok Dr. Davis, I really need your advice on this one. In following TYP, I have been taking 3200 mg day EPA/DHA fish oil 1.4:1 ratio. Recent testing shows I have gotten my HS Omega 3 Index to 9.5, and my Omega 6 to Omega 3 ratio to 2:9 so this pretty good. Now for the bad news....ever since I started taking 3200 mg day fish oil...over a 2 month period my HDL went from 48 to 38, a whopping 20% reduction in the critically important good HDL that I need to remove plaque. I exercise extensively, and I also take 10mg day crestor (crestor is one of the few statins that's supposed to raise HDL not lower it). Now, I have heard from several sources that Fish Oil (more than 1000 mg day) supplements are actually BAD for Apoe4/3 people because it lowers HDL. So now I am confused Dr. Davis.....do I follow your TYP advise and stay on 3200 mg day fish oil in order to keep a close to 10 HS Omega 3 Index....but suffer lower HDL and less plaque removal/reversal....or do I stop the Fish oil in order to raise my HDL but suffer the risks of little to no fish oil??

Please advise...

An extremely confused Apoe 4/3

Might-o'chondri-AL
11/7/2011 11:02:03 PM |

Hi Adam,
HDL drop can be due to accelerated small HDL's breakdown/clearance & if that was mostly lingering small HDL then it didn't have much reverse cholesterol transport function left in it anyway. If total HDL drops but small HDL turnover is now more optimal &/or if it is a greater % of the large HDL then there is better reverse cholesterol transport dynamic despite the total HDL drop.

ApoE has 299 distinct amino acid positions & the difference between the 3 types are due to which amino acid is in positions 112 & 158 ( respectively ApoE4 @112=arginine & @158 =arginine, ApoE3 @112=cysteine & @158=arginine, ApoE2 @112=cysteine & @158=cysteine). Because ApoE4 has arginine at position 112 this then orientates facing away from the standard grouping of 4 helix at that N-terminal to more closely cozy up to the alpha-helix of the C-terminal that in ApoE naturally overlays the N-terminal. Thus ApoE4 can uniquely feature a "salt bridge" to that C-terminal that affects how ApoE unfolds/functions when ApoE goes to work.
ApoE's manner of unfolding at it's N-terminal is crucial to how it deals with lipids, phospholipids (ex: cell membranes)and proteoglycans on a cell surface. Fish oil alters cell membrane phospholipid composition and then the proteoglycans there must suitably interact with that EPA enriched type of cell surface. Since each ApoE's C-terminal presents an interface that challenges how that ApoE works at any target cell the peculiar ApoE4 "salt bridge" uniquely conditions the way interactions play out. (And each of the separate 3 classic types of ApoE can get mutations, mostly at positions 136-150, to complicate degree of LDL receptor interaction, etc.)

James Buch
11/8/2011 3:14:01 PM |

Dear Doctor Davis,

I am wondering if you can clarify the "oxidized LDL Cholesterol" concept. Including, of course the Small LDL as well.

I began wondering if the oxidation is primarily in the package, the LDL wrap, the signaling protein, or the internal body of cholesterol itself. Of course, all of the above is also a possibility.

The nature of the oxidation could be a good clue as to how it is especially detrimental to health, and so far, I haven't found much easily available on the mechanisms of the detrimental effects. While it is useful to know the harmful nature of oxidized small LDL, some insight into the mechanism of harmful effects would be welcome and minimize the nagging question of "Why" for me.

josef
11/8/2011 5:07:20 PM |

This might be of interest:

A large study called the STRRIDE trial looked at the effects of different intensities and volumes of exercise on LDL particle size in sedentary, overweight men and women over eight months [3].  Group A performed 176 minutes of low intensity exercise (walking) per week.  Group B performed 117 minutes per week at a moderate to high intensity (jogging, cycling, or using an elliptical machine).  Group C exercised about the same amount of weekly time as group A, but at the same intensity as group B.

As one would likely guess, group C showed the biggest improvement in changing LDLs from small and dense to large and buoyant.  However, a more telling sign was that group B had a stronger effect than group A, despite exercising an hour less per week.  In other words, intensity is more important for improving LDL particle size than volume of exercise.

A follow-up of the subjects in this study showed some discouraging and encouraging effects on the particle size changes [4].  The discouraging news was that five days of inactivity following the study almost completely attenuated the particle size benefits from the trial.  However, before you start labeling exercise as futile, consider this: while five days of rest basically brought the exercise groups back to baseline LDL particle sizes, they were still much better off than the sedentary control group, who experienced significant digressions in particle size during the course of this study

Might-o'chondri-AL
11/8/2011 7:18:31 PM |

Hi James Buch,
The enzyme hepatic lipase's (HL) lipolytic hydrolysis of the phospho-lipids on the LDL surface changes it so that LDL's load of cholesterol esters can get taken out; this reduces the molecule's volume and thus is then small LDL (smLDL). Men have more HL than women, until they go through  menopause, and this propensity toward smLDL ( that can get oxidized) may explain male's earlier tendency of coronary artery disease. Visceral/central obesity trends to upregulate HL & it seems visceral obesity affects men more than women (of course central obesity in both women & men will raise both  genders'  HL enzyme levels). What decreases HL levels are things like calorie restriction & aerobic exercise (sedentary life increases HL).

Doc harps on avoiding elevated triglycerides after meals that load triglycerides into VLDL  molecules because the enzyme cholesterol ester transfer proetein (CETP) shunts triglycerides from VLDL (& chylomicrons) over to the standard circulating "big bouyant" (large & fluffy) LDL and fosters transfer of cholesterol out of that LDL; the triglyceride takes up less space and thus get smLDL.
Central obesity usually correlates with elevated triglycerides and increased HL levels. However, if triglyceride genetics (or epigentics from Doc's diet ,etc.)  in the obese without that usual accompanying high triglycerides then that upregulated HL doesn't cause a lot of that individual's standard "big bouyant" LDL to become smLDL. HL also hydrolysizes triglycerides (and phospho-lipids) of chylomicrons, BetaVLDL, IDL, LDL & HDL. Both CETP & HL enzymes being elevated alone, or together, can provoke smLDL - genetic polymorphisms exist for both enzymes.

sm LDL has less antioxidants left yet it's surface has higher ratio of poly-unsaturated acids which make it's phospho-lipids more at risk of oxidation. And smLDL has less sialic acid left on it's surface which fosters more poly-anion proteoglycan binding that increases the smLDL molecule's transportability across the endothelial lining into the artery wall .
Doc harps on need for Magnesium because in real time magnesium is what interrupts the oxidation of smLDL from locking into an altered state & then salvaged plain old smLDL doesn't get to go on to be so damaging.

Might-o'chondri-AL
11/9/2011 3:24:05 AM |

Continued for J. Buch,
Oxidized small LDL (oxLDL)  has fragments from it's oxidized PUFA (poly-unsaturated fatty acid) that are reactive aldehydes (ex: malon-di-aldehyde & 4-hydroxynoneal-lysine) which then fragment that smLDL's  lipoprotein ApoB.  That peroxidation of a PUFA acyl chain of  the smLDL phospholipid  leaves a type of carboxyl portion that the beta-2-glyco-protein I (Apo H) binds to using a "reactive" ketone as ligand link. Thus it is the position of the "reactive" ketone (keto-cholesteryl-9-carboxy-nonanoate) on the involved cholesterol molecule's spine that determines the % of glyco-protein bonding that occurs (genetics influences ketone placement on a human cholesterol molecule).

Magnesium (Mg++) in the very early stage of glycated protein (Doc warns against advanced glycation end products) hooking up with LDL reverses the glyco-protein link to the "reactive" ketone. But if deficient Mg allows time to consolidate that contact then only a physiologiclly abnormally high pH will let Mg re-break that bonding.

Immunological T cells respond (with age & gender differences)  to try to get oxLDL off the artery wall;  and, if there is too much to handle there is the risk of developing a so-called oxidized LDL-containing Immune Complex (oxLDL-IC). And this oxLDL-IC provokes cytokines that perpetuate the inflammation response. Over time and older age there is  less output of a malon-di-aldehyde oxLDL  immune response; which is possibly what leads to long established plaque having less lipid component and more involvement of collagen. It is relatively younger plaque that is unstable and more likely to rupture; the collagen draws in more Calcium and unfortunately provokes artery hardening problems.

Now the lipid part from this oxLDL-IC gets into an immunological monocyte cell's endosome  and the ApoB gets into that same monocytes lysosome - sub-compartments inside the cytosol (cell interior). Then the lipid part in the endosome triggers heat shock protein (HSP 70/70B) which wrenches things so that the lysosome can't get to work on the lipid and ApoB prevents the lysosome from doing proper interactions at the inside of that cell's membrane to expel  the burdens. Once oxLDL cholesterol esters bulk  up a macrophage (monocyte) due to increasingly futile lysosome  activity  it becomes the notorious "foam" cell. Eventually that macrophage cell dies and the whole load get's polymerized into plaque.

Might-o'chondri-AL
11/9/2011 8:03:57 PM |

Hi Dr. Davis - with your indulgence:
Back to platelets( see above Nov. 7): vascular remodeling with age &/or ROS exposes a bit of phosphatidyl serine  that platelets can "snag" onto as platelets flow along. Key to accomplish platelet snagging is signaling by  the promoter P2gamma12 and normally insulin signaling down inhibits P2gamma12. But, notably for Type II diabetics (and assumedly proportional to an individual's insulin resistance) their insulin doesn't inhibit that snag signal. Type II diabetics also have P2gamma12 upregulated in their platelets. And if anyone is of P2gamma12  haplo-type H2 those individuals will have even more of the receptors for it and therefore an  increased risk of peripheral artery disease. Irregardless of haplo-type, the Type II diabetic's propensity for peripheral artery problems are compounded by  their basal level of excess P2gamma12 .

Adhesion to the artery then physically involves the platelet surface Glyco-protein Ib & vonWillebrand factor hitched to collagen provoking Integrin 2beta1 (GPVI) so the platelet/collagen sets in place. If the level of promoter P2gamma12 in that challenged site is fortuitously low then the rate of adhesion to the blood vessel is poor. So, predictably, for Type II diabetics the adhesion rate (like platelet secretion & aggregation) is higher than normal. GPVI insult also signals a release of ADP & this ADP (like collagen itself) independently induces aggregation of platelets; the plaque recruits to build itself up to be more fibrous. The plaque matrix serves as nesting for oxLDL & dying macrophage foam cells to polymerize with.

ROS remodeling agents of the vasculature come from mitochondrial activity and  it appears certain (overlooked) relevant gene pheno-types (and their respective polymorphisms) can be pro-plaque (or preventative) - speaking here in the sense of  a primal influence on plaque risk as well as  tendency of the actual amount of plaque. Sirtuin 5 (Sirt5), a mitochondrial Sirt (there are nuclear Sirt too) binds to Uncoupling Protein 5 (UCP5) and governs that (& other) UCP. Sirt (there are 6 types) remodels chromatin (DNA spooled around a histone ) via histone de-acetylase enzyme; while our UCP (there are 5 types) work in the inner mitochondrial membrane governing the proton electro-chemical gradient that is integral to the chain of oxidative phosphorylation (a way to generate ATP, among other functions).

Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included.Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included. Doc's diet/protocol may ( I suggest) sometimes  tweak out favorable health response(s) via induced epigenetics, because of remodeling that is induced in the chromation DNA unit packaging . Sirt's histone de-acetylase working depends on NAD- to drive Sirt and Doc's diet/protocol theoretically seems to be capable of altering NAD flow patterns from his weaning of cells'  mitochondria off of glucose.

UCP5  rules the inner mitochondrial membrane potential & the rate of oxygen use, which can become relevant to ROS levels. Both UCP5 and Sirt5 are upregulated in hypertension and Type II diabetics; the confluence of having geneticly more UCP5 along with Sirt5 are implicated in increased carotid artery plaque. (Of course nothing is linear in humans so haplo-type T- carrier UCP5 polymorphism rs5977238 benefit with less plaque risk and reduced plaque numbers.) Note: I am skipping over other Sirt & UCP; but will add that lots of pheno-typic UCP1 spins out extra amounts of reactive super oxide to drive down nitric oxide and implicated in accelerated aging of the vasculature.

Jack Kronk
11/10/2011 8:13:40 PM |

Might/Doc - Does this mean that if you DONT have proper insulin receptor response that all of the things listed in the last paragraph become untrue? (meaning bad?)

Would this mean that you are implying a low carb diet would be the best solution due to the insulin issues?

I ask because I cannot raise my HDL for the life of me. It is completely stalled at 40. And my LDL is primarily small dense kind. I have only really had this problem since going "LC Paleo" and adding a ton of sat fat to my diet but then I added back in starches and other carbs and became more moderate carb, while still continuing to eat bacon/eggs/cheese/cream/butter/beef/coconut oil/ghee/nuts etc.

Now I've got people telling me to go back to LC, and exactly the reverse, people telling me that I need to cut out the fats including dairy and go low sat fat.

STG
11/10/2011 11:18:15 PM |

Mito....:
I have viewed your comments at the Hyperlipid and always appreciate your detailed biochemical/physiological explanations per topic. Your grasp of details and mechanisms is amazing! What is your background? Are you a biochemist by trade?

Kent
11/11/2011 4:34:12 PM |

A retreat is an excellent idea! It would be a great time of learning and discussions. I vote for Gulf Shores Alabama

Might-o'chondri-AL
11/11/2011 7:02:07 PM |

HI STG,
My hope here is that I never hijack Dr. Davis' blog ( I never personally posted on Hyperlipid blog). I trust Doc's readers know he is not responsible for any errors I make. Being semi-retired from consulting on agro-industrial projects in developing countries I feed my mind by keeping up with health science & commenting here about correlations to Doc's work.

Might-o'chondri-AL
11/12/2011 9:33:23 AM |

Hi J. Kronk,
Saw your 11 Nov. query &  feel diet advice here is for Doc to offer (not me). Doc discusses ApoE pheno-types he restricts dietary fat for. You "tagged" me where I  was elaborating on platelets' interaction with insulin & how insulin resistance is a game changer (not sure what confusing).

If one is insulin resistant then the signaling to build-up (anabolism) from insulin is selectively diminished and consequently break-down (catabolism) signals get  into play. Proteo-lysis is protein cleaving and HDL's protein component can be more rapidly subject to proteo-lysis; which I presume (?) is why/how some people degrade their HDL so quickly. Genetic quirks (& gender) also hit HDL levels notably;  yet  if quick enough turnover the "stale" HDL  might be being replaced by more functional HDL. According to the "HATS" study HDL alone is not a predictor of coronary artery disease mortality.

Niacin usually decreases rate of catabolism of HDL,  it helps secrete more ApoA1 to make into HDL & decreases amount of  smLDL. Niacin isn't perfect since it alters the extent to which HL (hepatic lipase enzyme) can work on a  HDL molecule to morph  it into the kind of HDL that has the maximum reverse cholesterol transport capability. HL is what hydrolyses the triglycerides in HDL - so, basicly if HDL loaded with trigs it has sparser room for scavenging cholesterol.

One's genetic response to increased levels of circulating palmitate free fatty acid can interfere with insulin signalling in the liver. Whether clinically insulin resistant or due to a genetic quirk (you?),  palmitate can phosphorylate liver insulin receptors in a manner unlike "normal" individuals do in the Akt process (insulin normally should get Akt going to stop liver gluco-neo-genesis - since insulin has glucose to drive into cells ). Essentially "excess" palmitate, in this example, is causing only a partial phosphorylation of Akt & is how researchers can use very high fat diets to induce experimental diabetes .

I don't hear you being insulin resistant, so address genetics of Protein Phosphatase 2A (PP2A), which  has components involved in it's regulation and is subject to different structure. How PP2A parts interact with distinct parts of the Akt molecule can  impair some interactions,  yet leave other parts of Akt responsive ( to do what Akt  is normally designed to do). Palmitate can raise PP2A levels in the liver by 30%; so basically the more PP2A  around and/or the molecule's genetic tweaks the weaker a key part of  the liver's Akt response is going to be.

Since palmitate  being in the liver does not stop insulin there from fostering more trigs there are still post-prandial trigs going into the VLDL . In other words the liver insulin resistance and rogue genetics can leave the part of Akt that governs lipo-genesis still responsive to insulin. Doc warns us about trig enriched VLDL & chylomicrons promptly driving  smLDL that doesn't degrade & small particle numbers measure high; he is more adamant about post-prandial trigs but genetic high overnight trigs can occur.

I don't think coconut oil acts the same way high animal fat sometimes does on Akt . We internally make palmitate when acetyl-CoA acted on by enzyme acetyl CoA carboxylase  to make malonyl-CoA that fatty acid synthase converts to palmitate. I think most of coconut oil's fatty acids are metabolized before getting into that pathway so maybe coconut oil is worth parsing when genetics or insulin resistance drives up smLDL.

STG
11/12/2011 6:16:07 PM |

Mito..
Excuse my error about you posting on the Hyperlipid. I guess I have read your posts elsewhere. In any case, your posts are very educational and explain precisely the biochemistry Thanks for sharing your knowledge!

Mark
8/14/2012 3:24:54 AM |

Hi Dr. Davis,
Iâ€™m 47 yrs old. Iâ€™ve had migraines since I was a teen and I developed Athsma this past January (hate it). During the process of discovery the drs found I have a 50% blockage in one of the 5, non critical, arteries running along the back of my heart. Scared me, to say the least. Iâ€™ve always eaten quite healthfully (for what I knew), am thin @ 6â€² 1â€³/155lbs (was 175lbs in Jan.). Had total cholesterol of 200/LDL of 146/HDL of 50. Drs wanted me to do Lipitor. Researched and said, â€œNo, thanks.â€ Started exercising 5-6 days/wk (lifting + walk/run), taking red yeast rice, fish oils, fish, no meat, no dairy, no eggs, lots of veggies/fruit, etc., but still eat beans, oats (every AM), occasional wraps. After 6 wks my blood work (VAP) was as follows: LDL=86, HDL=43, VLDL=17, TOT. CHOL=146, Trigycerides=66, Non-HDL (LDL+VLDL)=103.

Seemed GREAT to me! The dr wasnâ€™t impressed. Said my â€˜particle sizeâ€™ was small: LDL1(a)=8.1, LDL2(a)=0, LDL3(b)=39.5, LDL4(b)=24.9. Density Pattern=B.

Iâ€™ve continued but donâ€™t know how to elevate my HDL and reduce the particle size/change the pattern to the more favorable â€˜Aâ€™. Getting down about this. Working hard but, seems like I canâ€™t find answers that work, anywhere! What might you would work in my situation? Also, Is niacin ANDRed Yeast Rice a bad idea?
Iâ€™ll hang up and listen. Thank you,
Mark

PS - I left this post on another page, as well.

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