When a person decides to become optimal and eats a paleo/primal diet there are many changes that occur to one’s RNA/DNA and to our epigenetic switches. Many of these bio-machinations will take months to give the full hormonal response but there are some potential issues that can exist when a person implements a change to their life. One of the big issues is to initially delineate is what kind of paleo diet are you instituting? Many people eat a lot of grass fed skeletal meat and avoid all offal at first. Others cut their carbs while others carb load based upon their activity levels. Others use a high protein approach to control hunger while others use a low protein approach if they are running a vegetarian regime. This blog will attempt to discuss what someone might consider to supplement if they are eating a standard paleo diet as outlined in “The Paleo Solution or in Primal Blueprint.” Most people making the change to this lifestyle are coming to it from diet that is usually not optimal. Moreover, the USA food supply is so altered that most Americans are not getting the full nutritional value that they could or should get than out counterparts in the rest of the world because of the practices in the food and agricultural industry. These practices have been allowed to occur by the USDA and federal governments inaction on many fronts. Recent decisions favoring Monsanto being able to genetically modify seeds and alfalfa are examples. They have gone after small farmers who are farming organically and trying to sell raw dairy products. They have have also tried to make the lives of companies like Nutiva and Tropical Traditions miserable with regulations to protect genetically modified foods whose origins are usually from Monsanto. Given this legal and regulatory environment the person has to make some adjustments to offset the losses of nutrient density in foods available from this country. I think the world needs to pay attention to this because we are major exporters of our foods globally. This is really bad news for them. We know how bad this is for our country already.

1. DHA/EPA: The reason is simple. Most people start off their lifestyle change with excessive omega 6/3 ratio’s in their diet and tissues. I strongly recommend everyone getting a O6/3 blood assay done prior to making the shift. I did and mine back in 2006 was 37:1. Today its 3:1. I do not believe this would have been possible without the use of supplements because of how badly our food supply is loaded down with O6 and stripped of O3. Even the food sources naturally high in O3’s, like fish and meat, have been stripped by feeding farmed fish and cows corn and soy pellets loaded with O6’s. The levels one should shoot for is based upon your current O6/3 level and your highly sensitive CRP. Most people will fall between 1-4 grams. The more inflammation the higher dose I would consider.

2. A multivitamin is critical because of the various nutrient depletions in our food supply. Few people and their doctors are aware of how deficient we are in essential nutrients. We are down to the fundamental fact that the vast majority of Americans fail to obtain even the tiny amount of nutrients in their diets that the medical establishment itself says are needed. A paleo diet provides a far better mix than the SAD, but when one makes the change you are starting off with a deficit. This is why so many have bad body composition, poor energy levels, and altered hormones. For example, in the January 23, 2008, edition of the Journal of the American Medical Association, the findings from a study that measured vitamin E levels in people 65 years and older was published. The results showed that those with the lowest blood levels of vitaminE were 60% more likely to suffer physical decline over the three-year follow-up period. The same has been found for Vitamin D, Magnesium, Selenium and Iodine levels in various studies. Vitamin A is critical because optimal levels are needed to convert LDL cholesterol to the steroid cascade with T3.

3. Vitamin D3: Vitamin D3 is a pro hormone and is vital to immunity and to other physiologic functions. Vitamin D3 is an important neuro-steroid hormone responsible for many elements in brain development and behavior as well. Vitamin D3 increases brain levels of glutathione, a powerful natural antioxidant that is the body’s most important tool for detoxifying and excreting heavy metals and one that is rapidly consumed during oxidant stress from toxins and other sources. Vitamin D3 is made from LDL cholesterol in the steroid chain. Most vitamin D3 in the American food chain is added and is D2 not D3. This is especially true in dairy products. The active form of vitamin D is D3 and is made in our skin by sunlight. The best dietary source is from fatty fish or other animal products. Few people have good dietary sources of vitamin D3. Vitamin D3 can also be made from sun exposure but the dermatologists have done a masterful job of convincing many they will succumb from skin cancer if this is their major source. So most americans do not get vitamin D3 this way either. This is why we have an epidemic in patients with low vitamin D levels. Most americans fail to even get the low RDA of 400 IU from all sources. I would suggest you read my Vitamin D post here. For this vitamin I suggest a basal dose of 5000IU for most patients. For those who are suboptimal I will push this big time. And I am no fan of 50K of Vitamin D2 a week…….its suboptimal dosing with a suboptimal form of Vitamin D for humans.

4. Vitamin K2: In my practice I see a lot of osteoporosis as a spine surgeon. This vitamin is one I test for quite often and in my estimation there is a bigger epidemic in vitamin K2 levels than there is in Vitamin D3. The american diet is virtually depleted of K2. It is found best in raw dairy products but raw dairy is hardly available anywhere in the US. The pasteurization process virtually eliminates any K2 during this chemical process. Vitamin K is also found in green leafy veggies like Kale and spinach but its levels in non organic versions are dramatically altered. What does Vitamin K do to make it so important? Vitamin K is the cofactor for the enzyme, γ-glutamyl carboxylase, which converts specific glutamic acid residues in a number of substrate proteins to γ-carboxyglutamic acid (Gla) residues, which then serve to form calcium-binding groups in these proteins and are essential for their biologic activity. Carboxylation thus activates this family of Gla-proteins, which are involved in numerous essential activities throughout the body, including blood coagulation, bone metabolism, vascular repair, prevention of vascular calcification, regulation of cell proliferation, and signal transduction.

While osteoporosis is its own epidemic due to leptin resistance, heart disease is the number one killer of men and women in the USA. A clinical study from Rotterdam, Holland revealed a correlation between long term adequate Vitamin K2 intake and a lower incidence of calcification of the wall of the aorta. Arteries with no plaques have been shown to have a massive increases in Vitamin K2 concentration in their walls and plaques when compared to arteries with arterial plaques. Vitamin K2 depletion is critical in developing heart disease as seen in many longer term studies, like Framingham and the Nurse’s Study. There is a link of Vitamin K depletion in CVD, AD, and in liver cancer from viral hepatitis. Vitamin K is also recycled in the gut and uses the gallbladder as a conduit along with the enzyme VKOR. So in people without a gallbladder there is a very real risk of Vitamin K depletion. Most patients I have checked with a history of cholecystectomy also tend to have very low HDL levels and leaky gut. This is a big clinical pearl I look for. The lowered HDL level allows for poor endotoxin clearance in the portal circulation, and this increases the plasma’s ability to oxidize sdLDL cholesterol also a factor in development of heart disease as well. The daily dose needed by humans is only 45mcgs per day. Even with this low requirement we see a major epidemic in depleted vitamin K levels. Most vitamin K2 is made from the gut bacteria provided there is not dysbiosis. If there is then the clinical situation is worse. The best clinical measure of this is arterial calcification in the face of frank osteoporosis with a low HDL and elevated LDL. Most patents show a high sdLDL on VAP testing as well. There are three isoforms of K but my favorite for bone and heart are K2 MK-4 subfraction. I think a mix of all isoforms is good for most people (K2 in mcgs doses are fine for regular patients) but for my bone and heart patients with calcified vessels I put them on high dose K2 with MK-4 subfraction. Dosing can range 5-45mgs for these people.

5. PQQ: Many paleo folks may not even know what this is. I call it the long sought-after “exercise in pill form.” PQQ is pyrroloquinoline quinone and is probably the most important B vitamin when one is making the change from a sugar burning metabolism (SAD) to a fat burning furnace (paleo/primal). When I first began to blog I started with a deep mitochondrial series. I think many questioned why I did so. Well, if your change to a paleo diet it is really not maximized unless your mitochondria are optimal first. This was shown in the leptin series as well at the muscle level (Oprah post). In my Optimized Life practice, this is one of the first clinical moves I make to light the pilot light of the mitochondria. PQQ has two major effects that make it critical. One is that it stimulatory to mitochondrial biogenesis. If you read my mitochondrial series from June of 2011 you will see why this is critical to reengineer a human to optimal. Since I have written extensively about leptin, energy efficiency is critical to optimization. If one is energy deficient due to leptin resistance (hormone cascade disruption) or due to poor mitochondrial function (inability to make energy well) there is little chance of getting someone to optimal quickly. My leptin Rx solves the steroid cascade problem. PQQ is the tune up that the furnace needs. Remember that our mitochondria are the engines that drive our metabolisms. If one is devoid of energy we call that person a cadaver. If one is lacking in energy they are either leptin resistant or the owner of a bunch of bad mitochondria. Most people on a non paleo diet have a Nissan Sentra engine in their Ferrari body. There is a huge energy mismatch of what their bodies want to do and what they really can do. This obviously effects basic functions and the ability to exercise too.

The second major is glycation control from AGE’s and ALE’s. One of the major unspoken benefits of going paleo is the huge change in dietary carnosine intake. What is carnosine you ask? Carnosine is a multifunctional dipeptide that also interferes with the glycation process. Carnosine has been shown to inhibit glycation early in the process, thus helping protect against further damage as we age. Carnosine is found in large amounts in red meat. When one makes the change to paleo the substrate for electrons in our food is red grass fed meat loaded with carnosine. A person eating regular american diet is filled with mitochondria not optimally equipped to handle an acute change to massive carnosine. Some other little known facts in our community about carnosine is that its levels fall off rather dramatically in humans as we age. It has also been shown in research that high levels of carnosine are also seen clinically with humans with long telomere lengths.  (http://www.ncbi.nlm.nih.gov/pubmed/15474517)  This means they live longer lives. Longer telomeres are directly tied to mitochondrial health and optimal functioning. This biology was worked out by Nobel Prize winner Elizabeth Blackburn’s lab at UCSF in 2009. So it is clear that having great mitochondria is critical if you are going to make the superior substrate jump in a paleo lifestyle. It makes no sense biologically to eat great if your biological engine cannot harness that power to change your body. I recommend a higher dose for all paleo’s……20mgs a day. If I eat a lot of meat and coconut oil because I worked out hard I will go even higher.

6. Co Enzyme Q10: This one should be obvious given what I just told you about number 5. CoQ10 is a co factor in mitochondrial electron transfer and it many stress reaction biochemically in the body. So having this in excess is needed when we are going to be providing better nutrient density to the mitochondria to make more energy so we can increase our exercise ability. Exercise increases our oxidation from stress hormones. Most often exercise is hormetic when things are in balance. When there is a CoQ10 depletion by neolithic diseases, statins, or by being generally out of shape we need to increase dietary supplementation to optimize a paleo diet. CoQ10 comes in two formulations, Ubiquinone and Ubiquinol. One is an oxidized form and the other a reduced form. You can also tell by its cost. Ubiquinol is three times more costly because it is difficult to make in the reduced optimal form. Ubiquinol contains two hydroxyl (OH) groups instead of just one. This advantage allows it to bond with water molecules and makes it more readily absorbable by our mitochondria in our cells for energy production. Moreover, ubiquinol is the biologically superior form of CoQ10 because it’s an electron donor, which makes it a very effective neutralizer of free radicals and the only form of CoQ10 that scavenges lipid peroxyl radicals that can damage the polyunsaturated fatty acids of your cell membranes. In my view, this is a massive benefit when you’re eating paleo. Depletion of cellular CoQ10 will not even support basic cellular function. A Paleo diet and higher activity level require optimal mitochondrial and cellular function.

Remember that the heart muscle is critical to increase activity levels we want in a paleo lifestyle. Heart disease is a major killer in our country namely because of our diet. Findings at the 5th Annual International CoQ10 Symposium held in Kobe, Japan, demonstrated the superiority of ubiquinol in a group of seriously ill patients with advanced-stage cardiac disorders. If this can help people close to death with severe heart failure it is clearly critical to any human looking to optimize their life with a dietary change. This study revealed that clinically ill patients who suffered from severe heart failure readily absorbed ubiquinol CoQ10 into their bloodstreams (acutely and chronically by blood assays) and showed improvements in all health parameters. Another key point; those with autoimmune disease or hashimoto’s really need to use only ubiquinol because they can’t convert well from ubiquinone to ubiquinol due to low B6 and B12 levels. They need higher dosing often.

7. Minerals Selenium, Iodine, and Iron: This threesome are critical for thyroid function. The most common clinical scenario I see is thyroid disfunction. This is critical because if the thyroid is not working well T3 is likely not going to be available to convert LDL cholesterol to the hormones the brain uses to control our 20 trillion cells. Remember that T3 and Vitamin A is co factors in the conversion of LDL cholesterol to the steroid cascade. The first we will discuss is iron. Clinically, Iron is not important to supplement because the paleo diet is extremely robust in iron. But many of us forget our diet is only as good as what we absorb. If gut dysbiosis is present (usually is to some degree) or there is a lot of fructose in the diet iron absorption is a real problem. When one eats a lot of fructose in juices or in fruit (or HFCS products) you will increase your absorption of iron in the gut while also increasing your serum albumin. High iron levels are not good. High albumin levels can cause our free testosterone or estrogen levels to dramatically fall because the increased albumin binds them much like SHBG does in obesity or in hypothyroidism. None of this is good for optimal.

For the thyroid gland to produce the most active form of the thyroid hormone T3, selenium is essential but also helps regulate the amount of hormone that is produced. Remember T3 is a co factor in steroid cascades and also in reversing muscle leptin resistance at UCP3. We need 200 mcgs a day. Most don’t eat it. One brazil nut a day can do the trick. If you don’t eat them then I recommend a supplement every other day of 200 mcgs. Its dirt cheap and easy to find. Selenium is also critical in many stress related processes. Selenium is active in prevention of oxidative stress. Selenium works with a group of nutrients that include vitamin E, vitamin C, glutathione, and vitamin B3, to prevent oxidative stress. I wrote about selenium here in more detail.

Severe iodine deficiency can cause hypothyroidism. But many physicians believe iodine deficiency is rare in the United States and other developed countries since the addition of iodine to salt. I am not so sure about this. Again, just because its in salt does not mean we absorb it. I have found women are most at risk for poor absorption. One clinical finding I always ask about is the presence of fibrocystic breast disease. When it is present I immediately think the woman is likely suffering from an undiagnosed iodine deficiency. I distinctly remember in medical school seeing a woman’s fibrocystic disease cured in less than an hour by an ancient physician who taught us how to examine a women’s breasts. She had volunteered to be a guinea pig for us during our medical education, and on this day we could not examine her without making her scream and cry because her breasts were so tender to palpation. Our MD proctor was about 80 years old and he too was a volunteer helping us learn our craft. He stopped me from examining her breasts and asked her a few questions and then he asked us to leave the room. He applied Lugol’s solution to her vulva and her nipples and we were able to examine her without any pain a half hour later. It made a huge impression on me. He asked her if she was on any thyroid meds and if she had bad energy or weight gain. A lack of iodine was the source of her painful breasts. Her labs did not reveal any major issues when we saw her. I never forgot this lesson on the thyroid.

When one begins eating a paleo diet your nutrient density and food substrate improve so your iodine needs go up as your mitochondria are being asked to do more. So with a paleo diet you get a relative iodine deficiency for the first 3-6 months of the adaptation of the diet. I always as my patients to eat shrimp twice a week for the first 6 months or to supplement with a kelp pill every third day. That seems to do the trick for most people. Iodine 200-300 mcgs every other day if you eat seafood once a week. If you eat it more frequently you likely don’t need any supplementation. Se is one brazil nut a day or 200 mcgs a day. Fe is 325 mgs a day and take it with a vitamin C to increase its absorption and make you less nauseous.

8. Magnesium: Remember from the mitochondrial series or the Gnoll’s post that Magnesium is a co factor in making every last bit of ATP in the mitochondria. So if you don’t have optimal magnesium you are not going to be energy positive or optimal. T2D have the lowest levels of Mg I have ever seen. When people begin to eat paleo they usually are depleted in magnesium. They complain of poor sleep and develop constipation and muscle aches pretty often when they first adopt a paleo diet within the first few weeks. I offset this with a pretty hefty supplemented dose of Magnesium malate usually two hours prior to bed. If they need more I add a morning dose. This should never be taken with AM Vitamin D3 because they compete with one another for absorption. I am also a big believer in the use of Epsom salts topically in those with big depletion risks. There is another big benefit that comes with topical epsom salt use and that is increasing the sulfur intake topically as well. Those neolithic diseases include T2D, sleep apnea sufferers, restless leg syndrome, and those with fibromyalgia. Sulfur intake is notoriously poor in vegetarian diets and helps explain why they suffer from so many skin and connective tissue disorders (psoriasis, eczema, dandruff, folliculitis (infected hair follicles), warts, and pityriasis versicolor, vitalize are some). Sulfur is an important component of our body’s proteins. It is present in our hair, skin, nails and tendons, and plays a critical role in maintaining the integrity and elasticity of connective tissues too. After adopting a paleo diet, if the patient still complains of persistent skin issues I usually suspect a sulphur deficiency and recommend Epsom salt baths. Sulfur is an element that is part of four amino acids called methionine, cysteine, cystine and taurine. Sulfur is found in many animal meats and eggs, so longer term it need not to be supplemented on a long term paleo diet. This is very common in veggie to paleo conversions because they are so deficient and tend not to become ravenous carnivores right off the bat. So this is a real nice way to get some sulfur into your body to get optimal. If you need more you can consider a sulfur supplement like dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM). I like Magnesium malate 800 mgs two hours prior to bed. If you need more add 400 in the AM or eat dark chocolate daily.

9. B Vitamin Complex with Vitamin C added: They sell this really cheap in Sam’s Warehouse Club. IF you want a better source look for a B complex that includes S-adenosylmethionine (SAMe) too! If you do SAMe is usually in a B complex formulation because SAMe should be taken with cofactors vitamin B12 and folic acid. Our body requires methionine and vitamin B-12 to synthesize SAMe (also a Sulfur containing protein), a substance that is involved with the production of DNA. DNA is hereditary material in humans and animals found in the nucleus and mitochondria of nearly every cell in our body. The only people I do not recommend taking SAMe is those with bipolar disease. Published research shows that methylation defects create a variety of DNA/RNA age-related problems including neuronal and hepatic dysfunction. When we go paleo we are trying to optimize the liver and brain so this co factor is vital. Optimal methylation is critical for health and also a major factor in neolithic diseases like cancer and heart disease. In my view, you can not take enough B vitamins. They are critical. Always get your B12 level checked. Always try to make sure it is above 1000 on your testing. This is critical for optimal thyroid functioning.

10. DHEA/MELATONIN: Most people have sleep disturbances that I see prior to becoming paleo. The reason is usually a bad diet that causes spikes in inflammatory cytokines due to many factors. Sleep is critical to become optimal. This is when all cellular repair is done by our body. This process is governed by a cellular process called autophagy. Poor sleep is consistently seen with high levels of IL-6 in sleep research studies. DHEA levels tend to fall in both sexes dramatically after the age of 27 and directly correlate with poor sleep. DHEA decreases IL-6 in a dose dependent fashion but its use must be done with consultation with a physician. Many people use melatonin on their own for sleep but many do not understand the complex neural wiring between the brain, gut and pineal gland that must be taken into account before adding this to your routine. I find these two very useful in the first six months of a making a change to a paleo lifestyle. I use blood and salivary testing for tough cases to make a decision on care. I can not over emphasize how critical reestablishing optimal sleep is to this lifestyle. Melatonin you can start with low dose at 2-3mgs two hours before bed and titrate for effect. Highest I have taken myself was 20 mgs when I had serious jet lag. DHEA for guys I base it on labs but most can take 50-100mgs safely. The ladies should use the 7 keto version of DHEA and I would keep it below 50mgs a day without testing.

Dr. Jack Kruse

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