TO B OR NOT TOO B……..OR IS IT PROTEIN?

TO B OR NOT TOO B……..OR IS IT PROTEIN?

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READERS SUMMARY:

1. WHY IS PALEO PROTEIN CRITICAL TO CARTILAGE AND TENDON REPAIR?
2. HOW DOES PROTEIN HELP REPAIR CARTILAGE IN INJURY AND DEGENERATION?
3. WHY ARE B VITAMINS CRITICAL TO THE PALEO TEMPLATE?
4. WHY A PALEO TEMPLATE IS BEST FOR A PREGNANT MOM OR A YOUNG CHILD?

Today, we are going to go back to the top ten Paleo supplement blog and begin to talk in depth about why protein and B Vitamins are critical components to a paleo template. This is covered in levee 14 and 24 of the QUILT. One of the facets of this lifestyle is becoming active again. To become active and remain active requires a person to have optimal functioning cartilage, tendons, and muscle. As most of you know, I make a living operating on these structures, so I think have a pretty good understanding of how to make them optimal both before and after I have to treat them. This topic is also near and dear to me, because a meniscus knee tear is what got me to adopt this new lifestyle. If you listened to my podcast with Jimmy Moore, you might remember that I would not have any surgery until I repaired the nutritional deficiencies I thought were at the root of the problem. I significantly increased my protein and fat intake to give my body its best chance to heal that meniscus tear. I never got this advice from my consultant orthopedic surgeons. I got it from reading myself about how one should regenerate cartilage. To do so requires a lot of dietary methionine. The principal source of methyl groups is from methionine found dietary protein. SAMe (S-adenosyl methionine) is a principle example. The B vitamins choline, inositol, and B12, are some others. These are provided for in dietary abundance in most varieties of paleolithic diets. B Vitamins are used to transform the methionine to substance required to regenerate our cartilage. Methionine becomes SAMe using Vitamin B6 and Mg as cofactors. SAMe is the major source of methylation in our body. B Vitamins are involved in transmethylation, transsulfuration, and aminopropylation steps in the body. Most reactions involving B vitamins are characterized by being energy producing or anabolic, because they help in making us ATP. They also are vital for life and gene regulation. The B vitamins also are “the guardians” of our epigenetic switches that determine how our metabolisms respond to macronutrients. We have already seen how the new B vitamin PQQ is critical in exercise. Moreover, gene transcription is turned on and off by DNA methylation patterns. All the known DNA methyltransferases use SAMe as the methyl donor. So we will take a tour around our body’s systems to see what B Vitamins and protein do for us as we begin to optimize ourselves.

METHYLATION:

Methylation is not just one specific enzymatic reaction. There are hundreds of methylation reactions in all cells or the body. Methylation is simply the adding or removal of the methyl group (CH3) to a compound or other moiety. When some compounds receive a methyl group, this begins a reaction such as turning a gene on or activating an enzyme. When the methyl group is donated or removed, the reaction stops, or a gene or enzyme is turned deactivated. Some key methylation reactions would be:

1. Detoxification of dietary phenols from fruits
2. Methyl transfers turn on production of serotonin and melatonin
3. DNA methylation altering epigenetic signaling.
4. Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of particular CpG (cytosine-phosphate-guanine sites) islands.

The extent of both DNA hypomethylation and hypermethylation in the tumor cell is likely to reflect distinctive biological and clinical features of the cancer in question.
Not all people or cancers have the same methylation rates. Humans can be hypermethylators or hypomethylators. Some genetic diseases even show a pattern of hyper or hypo methylation. An example of this is Autism Spectrum disorders where 50{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of people with it are hypomethylators and 10-15{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} are hypermethylators. Cancer is another example. Neoplasia is characterized by “methylation imbalance” where genome-wide hypomethylation is accompanied by localized hypermethylation and an increase in expression of DNA methyltransferase

EPIGENETICS:

Methylation contributing to epigenetic inheritance can occur through either DNA methylation or protein methylation. You have heard about epigenetics in some of my other blogs. I have also commented on how transgenerational epigenetic signaling is critical to initially setting a fetus hypothalamus for its life. What the baby eats from its diet from 0-6 years old will set the hypothalamic switches of how calories will be partitioned from macronutrients. Research in humans has shown that repeated high level activation of the body’s stress system, especially in early childhood, can alter methylation processes and lead to changes in the chemistry of the individual’s DNA. The chemical changes can disable genes and prevent the brain from properly regulating its response to any type of biologic stress. Researchers and clinicians have drawn a link between this neurochemical disregulation and the development of chronic health problems such as depression, obesity, diabetes, hypertension, and coronary artery disease as the child ages.

DNA methylation in vertebrates typically occurs at CpG sites . CpG sites are cytosine-phosphate-guanine sites, where a cytosine is directly followed by a guanine in the DNA sequence. This methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. Human DNA has about 80{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6}-90{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of CpG sites methylated, but there are certain areas, known as CpG islands, that are GC-rich (made up of about 65{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} CG residues), wherein none are methylated. These are associated with the promoters of 56{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of mammalian genes, including all ubiquitously expressed genes. One to two percent of the human genome are CpG clusters, and there is an inverse relationship between CpG methylation and transcriptional activity.
Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence. Arginine can be methylated once or twice, with either both methyl groups on one terminal nitrogen or one on both nitrogens by peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice, or three times by lysine methyltransferases. Protein methylation has been most-studied in the histones. Histones directly control DNA/RNA binding sites for control of the epigenetic switches or for gene translation. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases. Histones that are methylated on certain residues can act epigenetically to repress or activate gene expression. Protein methylation is an example of one type of post-translational modification.

CARTILAGE OPTIMIZATION:

Chondroitin sulfate, glucosamine sulfate, N-acetyl glucosamine, hyaluronic acid, and mucopolysaccharides are all building blocks of cartilage, and they are all dependent upon sulfur groups for complete synthesis of healthy cartilage tissue. So you might be asking yourself where does the sulfur come from? It comes from methionine’s break down to homocysteine. This releases a toxic sulfite molecule but it is immediately bound to Molybdenum and this liberates a non toxic sulfate molecule. The free sulfate group then is able to regenerate our cartilage and tendons. This is very important when you are lifting and squatting with heavy weights and running sprints.
This process uses SAMe (S-adenosyl methionine) as the methyl transfer moiety between methionine and homocysteine. The methyl donations from SAMe , which are also used for the synthesis of neurotransmitters, and essential cell components such as phosphatidylcholine and phosphatidylserine in myelin sheaths of nerves or in the adrenal cortex. SAMe has also been used by itself as a nutritional supplement, but when you look at the pathway’s inner workings, unless you have all the necessary components available to optimize the efficiency of the whole pathway, SAMe can metabolize to homocysteine in just two more metabolic steps! This can lead to a large rise in homocysteine. I always ask if someone is supplementing with SAMe for this reason. To detox the high level of homocysteine, we need Vitamin B6 and Magnesium as a cofactors. If either one is deficient this will also lead to a build up of homocysteine on your lab values. This is why we use homocysteine levels as a clinical marker for problems in methyl transfer reactions. This is especially true in the cardiovascular system for poor energy utilization. It is also why I generally do not recommend supplementing with SAMe at all.

High levels of homocysteine clinically is a marker of disease and poor energy utilization. Other conditions which have been linked to high homocysteine levels include: Cardiovascular disease, Multiple sclerosis rheumatoid arthritis, spontaneous abortion, placental abruption, renal failure, and type II diabetes.

HEAVY METAL CLEARANCE:

The same reaction occurs in the liver and excess sulfate is utilized for detoxification that bind heavy metals such as lead, mercury and cadmium. So if one is B Vitamin deficient, you may be more susceptible to heavy metal toxicity if your body or diet contains them.

DEPRESSION:

Homocysteine levels are related to depression in several ways. The methyl group metabolism provided for by the pathway of homocysteine (when correctly functioning) is necessary for the production of depression-relieving neurotransmitters such as serotonin and dopamine. The B vitamins are also crucial in the direct synthesis of the brain neurotransmitters. Aside from the fact that they are needed (especially B-6, B-12 and folate) for the homocysteine pathway to provide methylation, they are essential to the pathway of making these neurotransmitters . The neurotransmitter acetylcholine also is involved with homocysteine as well. High homocysteine levels have been linked to Alzheimer’s disease. This occurs due to poor energy utilization leading to protein folding problems that cause the development of the neurofibrillary tangles. The tangle appears to affect oxygen utilization in the neurons and renders them unable to produce acetylcholine, the brain neurotransmitter necessary for thought processes. Many times when one makes the switch to paleo, people will complain of “paleo flu”. Often this “flu” is poor methylation that causes a low energy state. Testing easily can pick this up.

CITES:

J Affect Disord. 1986;10:9-13; Psychosomatics. 1980;21:926-929
Fava, M et al., Folate, B-12, and homocysteine in major depressive disorder. Am J Psy 1997;154:426-428
Christopher Walsh (2006). “Chapter 5 – Protein Methylation”. Posttranslational modification of proteins: expanding nature’s inventory. Roberts and Co. Publishers. ISBN 0-9747077-3-2.

Caldji, C; Hellstrom, IC; Zhang, TY; Diorio, J; Meaney, MJ (2011). “Environmental regulation of the neural epigenome”. FEBS letters. doi:10.1016/j.febslet.2011.03.032. PMID 21420958.

Champagne, FA; Curley, JP (2005). “How social experiences influence the brain”. Current opinion in neurobiology 15 (6): 704-9. doi:10.1016/j.conb.2005.10.001. PMID 16260130.

Champagne, FA; Weaver, IC; Diorio, J; Dymov, S; Szyf, M; Meaney, MJ (2006). “Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring”. Endocrinology 147 (6): 2909-15. doi:10.1210/en.2005-1119. PMID 16513834.

Felitti, VJ; Anda, RF; Nordenberg, D; Williamson, DF; Spitz, AM; Edwards, V; Koss, MP; Marks, JS (1998). “Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study”. American journal of preventive medicine 14 (4): 245-58. PMID 9635069.

McEwen, BS; Gianaros, PJ (2010). “Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease”. Annals of the New York Academy of Sciences 1186: 190-222. doi:10.1111/j.1749-6632.2009.05331.x. PMC 2864527. PMID 20201874

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45 Comments

  1. BeingVenus October 5, 2011 at 4:15 pm - Reply

    How do you optimize those first 6 years? It seems like the only time in your life you have the ability to shape your child's future health. Obviously sunshine, breastfeeding, and a paleo diet but is there anything in particular you've found in your reading that most parents wouldn't think of immediately? I only ask because I have a 10 month old who is just starting to eat more solid foods and always wonder what I should be giving him. He mostly gravitates towards fatty meats on the bone, dairy, fats, and fruit. Doesn't mind veggies or tubers as long as they have butter or coconut oil on them, spits out anything with liver, seafood, or egg yolk in it (much to my chagrin,) and of course, it mostly breast fed. Is there any research on child health and macronutrient ratios in the formative years? How much D should children be getting? If you had to do it all over again how would you have fed your children?

  2. Christina October 5, 2011 at 5:13 pm - Reply

    Thanks for throwing in the role of b's in depression. Brilliant stuff. I wonder how many people on PPI's are walking around depressed and with poor cartilage.

  3. BeingVenus October 5, 2011 at 5:55 pm - Reply

    Interesting N-1. I found that after going paleo (a month after giving birth) and supplementing B's my Breast milk turned a beigey yellow color. I'm sure that we are starting life from the very beginning in many cases, deficient in these important vitamins. One need only look at the difference in color between store bought pasteurized cow milk and raw grassfed cow milk.

  4. Cody October 5, 2011 at 6:21 pm - Reply

    Doc, I have this flu. I gave up coffee when I took up strict paleo a few weeks ago and my energy levels are extremely low.

    I feel tired and foggy (similar to low blood sugar episodes) and any kind of activity is uncomfortable, even walking up stairs. My muscles almost kind of hurt.

    I am on Vitamins A, C, D3, E, K2, Sublingual B complex, and Minerals Magnesium and Selenium, as well as Ubiquinol. I drink Tulsi Tea in the morning, take Ashwaganda first thing in the morning on an empty stomach, and also take a gram of milk thistle and a gram of Turmeric. At night, I take valerian before bed if I don't feel tired (~3 times per week).

    I eat zero carb. Breakfast is a 73/27 ground beef patty and eggs along with a shake of coconut milk and 2 raw eggs.

    Light or no lunch.

    Dinner is fatty meat and sometimes pork rinds.

    I drink water and sometimes Zevia.

    Only weight loss has been water weight thus far. I started at 456 lbs 5 years ago, and currently weigh ~325. Lost my weight using low carb/psmf and am stuck.

    I know that you cannot answer specific health questions, but in general, when one experiences this "flu" what supplements, herbs, etc. help the most?

    Also, in my shoes, what tests would you have done? What should I look for? Any chance you do phone consultations?

  5. steve October 5, 2011 at 6:21 pm - Reply

    Histones that are methylated on certain residues can act epigenetically to repress or activate gene expression.

    How is this related to Atopic problems- hay fever,eczema, and how would you suggest addressing these problems?

    Thanks.

    • Jack October 5, 2011 at 6:28 pm - Reply

      @Steve They are related and this will be covered in coming blogs. Next up we are going to get more clinical in the blog.

  6. Cody October 5, 2011 at 6:27 pm - Reply

    I would like to know as well (Steve's question) as my daughter suffers from horrible asthma, allergies, and eczema.

  7. BeingVenus October 5, 2011 at 7:02 pm - Reply

    @Cody I had childhood asthma, and generally bad breathing as an adult until I went paleo and started megadosing my vitamin D. Get lots of coconut oil and vitamin D in to you daughter. I didn't find my symptoms going away (tight chest, snoring, colds) went away until my D levels were around 65. I also take vitamin K2, zinc, drink a crap ton of green tea, magnesium, and eat lots of offal and shellfish.

  8. Cú Chul October 5, 2011 at 7:27 pm - Reply

    What are the best sources of methionine? Art De Vany recommends BCAA powder on a paleo diet while trying to build muscle–"Powder is the only way to get 5-10 grams. The BCAAs may be only 4 amino acids or may have many. Read the label. I would like to see methionine among the ingredients; the Axis brand lacks it. Methionine fuses proteins together to make tissues."

    I have not been able to find an unsweetened BCAA powder including methionine.

  9. Jack October 5, 2011 at 7:39 pm - Reply

    This blog I wrote in July really plays into the B Vitamin story and methylation story found in todays post…….so if you have autoimmune disease read this link. You may start seeing how these concepts are married biologically.

    http://jackkruse.com/why-leaky-guts-lead-to-ms/

  10. Jack October 5, 2011 at 7:44 pm - Reply

    @Cu Chulainn Art is right about building muscle. BCCA's are very insulinogenic and stimulate the AMPk pathways……but there is no data that chronic use is good. In fact there is a lot data that says chronic use of BCCA's stimulates insulin and IGF1 pathways as we age and this limitis longevity. My take on this I am OK with increasing IGF1 and mTOR pathways (both not good in most papers on longevity) provided that the surrounding cellular terroir is very antiinflammatory. This means a very low plasma and tissue o6/3 ratio and a brain, liver and muscle layer that is supremely leptin Sensitive. To get this the first step is to make sure one is leptin sensitive……it underpins all longevity and optimization and why it sits at levee two in my quilt. People who are extremely LS can handle BCCA's. Art is one of those people. There are not too many 70 year old Art DeVany's or Jeff Life's around. I am to be one of them. Making sure your O6/3 ratio and HS CRP are small are among the best ways to guarantee that outcome in my view.

  11. Jack October 5, 2011 at 7:45 pm - Reply

    The best source of methionine to me is grass fed red meat. Not BCCA's because BCCA's are all processed.

  12. Jack October 5, 2011 at 7:46 pm - Reply

    @Being Venus……totally agree with you on the Vitamin D and coconut oil. There is no better way to increase ones immunity faster.

  13. Jack October 5, 2011 at 7:48 pm - Reply

    @Cody……you really need to read the monster MDA thread. The answers to your problem are all there. If you follow the Leptin RX you will eventually get to your goals. It however is going to take a long time because the backround cellular inflamamtion will slow the underlying reset of the hypothalamus. If you want to step it you will have to test. I have written extensively about the testing in most of my writings and in my optimizing labs blog. You might want to check it out.

  14. Cody October 5, 2011 at 8:11 pm - Reply

    Yes, I'm following your Leptin RX. Even before true paleo. I've been doing it for 2 months.

    Thanks for the hints!

  15. Cody October 5, 2011 at 8:17 pm - Reply
  16. Cody October 5, 2011 at 8:18 pm - Reply

    Sorry, I believe it is this one:

    http://www.marksdailyapple.com/forum/thread32345….

  17. Cú Chul October 5, 2011 at 8:45 pm - Reply

    five years ago I had arthroscopic surgery on my knee, removing arthritic damage & cleaning up a meniscus tear & loss of 1/3 of ACL–doctor says all three kinds of damage will inevitably progress–anything I can do to arrest this progression?

  18. steve October 5, 2011 at 11:49 pm - Reply

    Jeff Life? Dr. Life uses Human growth hormone i believe. Are you an advocate of it-Cenegenics?

    Thanks

    • Jack October 6, 2011 at 12:30 am - Reply

      @Steve I am advocate of optimal. If you are growth hormone deficient by testing, I see zero problem using it. The part that few seem to know is that very few people qualify for growth hormone because they dont test for it correctly. As a neurosurgeon who see many tumors and trauma in and around the hypothalamus I have seen huge homeruns from GH replacement. In fact, one of my fellow physicians had an unfortunate issue occur to them and they needed it after having an arginine suppression test done. No one can get growth hormone now with out proper testing in our country. This has changed the situation that existed in years past when anyone with money could buy GH. You must have a medical indication to get it now.

      The docs transformation to optimal health has been nothing short of a miracle. They went from the brink of retirement to back to full time work. And this doc is a paleo physician too. I say this with major pride. We need as many paleo docs as we can get. This person also had heart failure and there VO2 max has improved dramatically with treatment. I view GH treatment just like I look at insulin treatment for a T2D.

  19. Dru October 6, 2011 at 1:06 am - Reply

    What about using GH for the sole purpose of cartilage/tendon regeneration?

  20. Andrea October 6, 2011 at 11:40 am - Reply

    So it's beef stock and supplements and homocysteine testing for cartilage rehab?

    But what about the connection between Leptin and cartilage? There is some stuff on pubmed)(starting with a french publication in 2003).

    Is Leptinresistance bad for cartilage and can Leptin Sensitivity help?

    Or is the damage from your mother during pregnancy being LR? Or is it lack of breastfeeding because the child doesn't get the Leptin from milk?

    In short: what to do in which order to optimize cartilage besides healthy eating and movement? And what if someone has chronic inflammation from food sensitivities? No chance for cartilage healing?

  21. Jeff October 6, 2011 at 1:47 pm - Reply

    Doc, the lab normals I've seen for homocysteine are 0-15, mine is at 8. That still seems a little on the high side. Where do you like to see those levels?

    I eat about 4 servings of liver per month, and sometimes supplement B complex. If I take even 100%RDA of the Bs for more than 2 days in a row I can't sleep and feel wired. Is that a sign of some other issue?

    thanks

  22. pam October 6, 2011 at 7:48 pm - Reply

    quote from Jack: "This is why we use homocysteine levels as a clinical marker for problems in methyl transfer reactions. This is especially true in the cardiovascular system for poor energy utilization. It is also why I generally do not recommend supplementing with SAMe at all."

    Interesting observation. Because for 2 years I played with various doses of all Bs, but only the addition of 200mg SAMe finally brought my homocysteine below 10 (now at 8). So I'll watch that this doesn't backfire in time.

  23. Cody October 6, 2011 at 8:19 pm - Reply

    Here is the good doc's recipe for dealing with the low carb or paleo flu from http://www.marksdailyapple.com/forum/thread32345-

    The gut issue and depression is tied to serotonin stores. When you go paleo and do the leptin reset you are immediately changing the serotonin level in your small bowel. Carbs metabolize to serotonin in the small bowel and are sotred there for use later in the brain. The rest of the serotonin is sent to the brain by way of the pineal gland. The rest is stored there. When darkness is preceived by the retina a signal is sent to the pineal to convert the 40% stored serotonin to melatonin. It takes four hours of darkness for this to occur. Hence the reason you need to keep in dark lit conditions as soon as possible when you cant sleep. Its a way to jump start the conversion. Once the conversion occurs the serotonin in th epineal is used and replenished by the gut stores…….so if you are rapidly eliminating carbs…….from the paleo diet and leptin reset you feel the pinch. This is what you all call the paleo flu……..you can offset it two ways…….4-6 weeks of 200mgs of 5htp A serotonin precursor…….or replacing the brain signal to the gut to give up more serotonin it does not have……this is done by the incretin neurons. They immediately get turned off by MCT in the proximal small gut. That is how coconut oil works. It has no effect on serotonin stores but makes you feel better.

  24. Laurie Herscher October 7, 2011 at 7:29 pm - Reply

    Hi Jack,

    It's your radiation oncology buddy from AHS here. I have another question about a patient I'm seeing that ties in with this blog so I'm commenting (please tell me if it's not appropriate here). Patient is a 65 y/o morbidly obese woman with gastroesophageal cancer who will be getting neoadjuvant chemoradiation then possibly surgery if her surgeon thinks she's medically operable–her problem is she is essentially wheel-chair bound because of severe osteoarthritis and severe lower extremity weakness (when she moves, it hurts so now she doesn't move; she told me she's been worked up for lupus, lyme disease…)Her surgeon told her she needs to get buffed up for surgery and recommended pulmonary rehab. Based on this blog, I want to recommend to her B complex, magnesium, eat lots of eggs. I hesitate to recommend SAMe because of her cancer. I'm not looking for optimal here, just better. She's on synthroid, too, so I was going to check her thyroid studies. Amazingly, she's not on a statin. I also think she could benefit from ubiquinol. Am I on the right track? Anything else you would recommend? Thanks much, Laurie

    • Jack October 8, 2011 at 4:12 am - Reply

      @Laurie Please text me your number. I deleted it by accident. Your case is a good one. I think you are reading it well but let me give you a couple more things to consider. She is on synthroid. Remember what I told you about synthetics vs bioidenticals? Or better yet remember Matt LaLondes lecture at AHS. Synthetic never equals bioidentical. SO I would switch her to T3 like cytomel or Nature thyroid. Since she has cancer she is also likely not going to convert T4 to T3 either. Synthroid is a T4 only drug. It requires transformation 80% of the time in liver and 20% in the small bowel. So here two more big problems. Synthroid in cancer (high TNF alpha and IL6) cause T4 to become reverse T3 which is a competive inhibitor to T3 and it shuts down her thyroid totally. This destroys her Vitamin D levels, pregnenolone, DHEA, sex steroids, and progesterone……all not good. And she has a high GI cancer…….too boot……so her T3 from the gut is not happening either. This will lead to a very high LDL and low HDL level. Since her rev T3 is high we need to really knock her hard with omega three's to improve plasma and tissue O3 ratios. This will help gut repair, help lower rev T3 too. I would also load her with Selenium and iodine to max out her thyroid. Check her serum ferritin if it is low she may need some Iron too for thyroid. As for your work on her……she need very high dose curcumin before you give her radiation or chemo. (it sensitizes cancer to effects of both) I would also load her up with lots of resveratrol……..as much as she can afford. I would also put her on 1200 mgs of Mg a day divided and four B complexes a day and high dose Vitamin C……….Let me know how it goes and text me your number.

  25. Andrea October 8, 2011 at 7:04 am - Reply

    Dr. Kruse,
    so what is the connection between cartilage optimization/degeneration and Leptin Resistance?

  26. pam October 8, 2011 at 11:20 am - Reply

    quote: "Check her serum ferritin if it is low she may need some Iron too for thyroid."

    Since I saw conflicting information about, what are the levels of ferritin you're recommending for optimal thyroid functioning?

  27. Jack October 8, 2011 at 2:02 pm - Reply

    @jane. Regarding your niacin email. It is a B vitamin and not in my top ten. I use it when its called for. I think too many functional docs go hog wild with it. If you are an hypomethylator (seems your are) you will get niacin toxic at much lower doses than other folks. I have one person who became a strawberry with 50 mgs and they had a horrible homocysteine level. In cases like that i consider a change to betaine hcl (also a methyl donor) and load the diet with fermentable carbs and coconut oil to force a microbiome evolutionary change. (LOL) Takes about 6-12 months for 68% of people. This maneuver increases K2 gut bacterial production, decreases fungal types, improves gut lining and mucous and stool caliber and regularity. The main physiologic effect is it increases the formation of butyric acid in distal gut and really helps those with diverticulitis, ibd, crohns, uc, and eosinophilic esophagitis which is now a full blown epidemic in kids and young adults in usa.

  28. Jack October 8, 2011 at 2:05 pm - Reply

    @andrea. Leptin problems are the source of all cartilage problems. This is a foundational pillars in how i treat back and neck pain. More on that much later. Take a look here:

    http://www.aaos.org/news/aaosnow/sep10/research4.asp
    http://arthritis-research.com/content/12/3/R95

  29. Jack October 8, 2011 at 2:09 pm - Reply

    @pam. It completely depends upon the backround clinical picture……most paleos have a ton of dietary fe from meats….but most SAD eating patients with hashimoto's have to really be careful with Fe, Se, and I. Zn and Mg levels too. Thyroid screws more clinicians uo than any other endocrine response. Its is our metabolic "gas pedal" while our leptin sensitivity at the liver level is the ferraris engine. The thermostat is hypothalamic leptin optimaztion.

  30. pam October 8, 2011 at 2:39 pm - Reply

    I'm a male vegetarian with ferritin levels from 76 two years ago, via 56, to the most recent with 94 ng/ml.

    In hair tissue Fn, Se and Mg have all decreased from last year – however, only Na and K a bid below the reference range – and despite having supplemented all of these minerals at usually sufficient amounts.

    No thyroid antibodies, but slightly enlarged thyroid with good response to 12mg/d iodine. But still very far from optimal with TSH 2.06, fT3 2.07 and fT4 1.83.

    So in my case, shout I be satisfied with a ferritin at least above 70? – would above 100 still be better? – Or as still others recommend, with arteriosclerosis one better get it below 35?

  31. Jack October 8, 2011 at 11:15 pm - Reply

    @Jeff I think it could be something else. You might even be a hypomethylator.

  32. Jack October 8, 2011 at 11:25 pm - Reply

    @Pam If the thyroid is enlarging you can try to out supplement the real problem but I don't think you will be successful long term. The reason you are not absorbing them is the real issue. You likely will have to go supraphysiologic in your supplementation to overcome your dietary limitations.

  33. pam October 9, 2011 at 12:00 am - Reply

    Thanks. Could I take it to mean a ferritin above 100 would be better?

    • Jack October 9, 2011 at 12:53 am - Reply

      Pam in your case you might consider it even higher. If you supplement with Iron make sure you do it with Vitamin C at same time.

  34. Andrea October 9, 2011 at 8:07 am - Reply

    OK, so I will wait for your next posts about Leptin & cartilage. I just fed Google scholar with "leptin" and "cartilage" and I got 552 hits for the year 2011 only! I will do a little reading. Sigh…..It's strenuous to be your own MD because your MDs give shit about health and therefore have not much knowledge except about "treatments" (drugs and surgery).

  35. Jack October 9, 2011 at 10:01 pm - Reply

    @Being Venus I think you should also take a re look at this blog on transgenerational epigenetics I wrote a while back and really read the cites. You may gain a real incite into why I am a stickler for the age of six. Moreover, I am an ardent believer in neuroplasticity but it appears when it comes to the hypocretin neurons they are a tougher nut to rewire.

    ttp://jackkruse.com/developmental-origins-of-disease/

  36. Jack October 9, 2011 at 10:03 pm - Reply

    @Andrea I fell prey to that as well with my knee injury so I took the situation into my own hands and read up on all of it. I am glad to say it may have saved my life as well as my knee.

  37. Andrea October 10, 2011 at 8:50 pm - Reply

    Thanks for the links Doc. The "Leptin-Cartilage" Papers already pile up on my desk. Should I measure my serum leptin level? It seems to be tricky: Some Leptin helps cartilage repair, to much of it seems to be dangerous. Sooooo….how much is too much?

    I am in trouble because besides cartilage problems I got a nasty food sensitivity (histamine intolerance) and this means: chronic low grade inflammation. Very bad for any healing whatsoever. Paleo Diet doesn't heölp so I will try Dr. Natasha Campbell-McBrides GAPS Diet. She says: Fix the gut and most food sensitivities and "allergies" will take care of themselves. I hope it's true. So it's basically only meat stock for several days.

    Greetings from your ….uhm..maybe 6th reader in Germany. Just kidding – I am sure we are more. 🙂

  38. Lo October 10, 2011 at 10:19 pm - Reply

    How does one know whether you are a hypo or hyper methylator? I've been taking 800mg of SAMe for at least a year now to help with mood stability (and it works! LOL!) so I'm loathe to ditch it… but I also don't want to cause other issues. Are there tests I should ask my doc to run?

    Everything else you mention here I've got a decent handle on (I think) as far as supplementation (I take a multi, D3, Mg, Zi, PQQ, B-complex, B-12, C, CoQ10, Resveratrol, adrenal support, L-theanine, Tryptophan, Niacinamide, Melatonin and I drink a good amount of green tea most days.

    I'm also recovering from shoulder surgery (torn RC) and I want to leverage my diet to help the healing (I'm 46, so, not a spring chicken any longer… but far from "old" 😉 so I am eating cleaner than ever… no added sugars, limited nuts, loads of grassfed/finished beef, pastured pork, pastured eggs, pastured butter, pastured cream (in my one cup of decaf), wild salmon, shrimp, and tons of local, organic veggies (though, I'm having to switch to "conventional organic" because our growing season is over for all but cool weather crops.

    Anything else I should be doing?

    Thank you so much for sharing your expertise with all of us. Your blog is incredibly informative and inspirational!!

  39. Jack October 11, 2011 at 1:26 am - Reply

    @lo. Depends on disease state. In cancer, autoimmunity and HIV its pretty easy. One can use an HERV test. For someone who does not have those diseases we can use glutathione levels which will be low, with low SAMe levels and high homocysteine levels. I hope this answers you Lo.

  40. Lo October 11, 2011 at 3:16 pm - Reply

    So, I have Hashimotos (which is auto-immune, right?) so I should ask for an HERV test? And that will tell me how I methylate? What sort of numbers do I look for?

    Or should I just do the glutathion levels?

    Thank you!

  41. My Program | Against The Grain June 16, 2012 at 8:22 am - Reply

    […] C is 150mg/day.  Reason for taking: I won’t try to summarize the benefits of B vitamins, as there are many.  Suffice it to say they’re good if you have a tendency toward depression (as I do), and are […]

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