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Angiex Doses First Patient in Clinical Trial of AGX101!

Posted by on August 7, 2024 15 comments

I’m pleased to announce that Angiex has dosed the first patient in our Phase 1 clinical trial of AGX101, Angiex’s lead drug.

As some of you know, 9 years ago Shou-Ching and I suspended our blog and health retreat to create Angiex. It’s been a busy and exciting nine years, and I’m looking forward to telling you about the special biology Shou-Ching discovered and the drug we’ve made in the weeks ahead.

But for today, I’m happy to simply savor the accomplishment of finally having the opportunity to test what we’ve made in clinical cancer patients. This is the fruit of 20 years of biology research and 12 years of drug development. Please keep an eye out for upcoming posts, and say a prayer for the success of Angiex and the cancer patients we are treating.

Some links:

AGX101 first patient dosed

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Vitamin C: Should you take it before and after surgery? Part 2

Posted by on April 17, 2014 6 comments

In Part 1, we found that taking vitamin C after orthopedic surgery is a good idea, and that vitamin C could help in other surgical situations as well. But that’s only half the story. Here’s the other half.

Vitamin C as a prooxidant?

The world of vitamin C was tipped upside down in 1998, with the publication of a controversial paper in the prestigous journal Nature entitled “Vitamin C exhibits pro-oxidant properties”. News media was all over it, predictably warning readers to be afraid…very afraid of taking vitamin C supplements. But the paper had a lot of holes, to put it mildly.

The study showed that some DNA was oxidized by vitamin C, but some DNA was also protected from oxidation by vitamin C (with the protection being around ten times greater in magnitude! A fact that was conveniently left out of the paper.). Plus the experimental technique may have oxidized some DNA by itself. So what happens when throngs of angry vitamin C supporters wrote in to the journal? The primary author backtracked, and his reply concluded “our study shows an overall profound protective effect of this vitamin.” Case closed. Or is it?

IRONing out the details…

Vitamin C is neither always an anti-oxidant or always a pro-oxidant, and not all studies are applicable to what goes on in your body. Take lab mice for example. Unlike humans, mice can synthesize vitamin C, and supplementation can paradoxically reduce their vitamin C levels. In humans, study results are mixed, with most showing either an anti-oxidant effect or no effect, and some showing both anti and pro-oxidant effects. Timing could also be an issue. In a study where vitamin C was added before LDL was experimentally oxidized, it displayed antioxidant properties. But vitamin C actually showed prooxidant properties when added AFTER the LDL was mildly oxidized. So what does this mean for surgery?

First things first: if you have iron overload (for example, due to hereditary haemochromatosis), be careful with high doses of vitamin C, especially during times of surgery. Unbound iron can interact with vitamin C to produce oxidative stress. Iron is typically bound to transfer proteins and largely safe from vitamin C, but a portion of iron stores may be released when tissue is injured and blood vessels are compromised. And when is a large mass of tissue injured? Surgery!

For people without iron overload, the implications of iron and vitamin C interactions are not so clear. There doesn’t seem to be much data about the interaction of vitamin C and iron during the surgical and post-surgical period. In vitro and trial evidence conflicts on whether vitamin C protects or chemically reduces (i.e. harms) iron in humans, and evidence is also mixed on whether vitamin C protects or occasionally causes protein glycation. Vitamin C can have differing effects on oxidation of depending on the target (lipids, proteins, or DNA) as well.

So the takeaway here may simply be: avoid taking supplements that contain iron and too many iron-enriched foods around surgery time (unless you are advised to by your doctor), and don’t go much beyond the PHD-recommended vitamin C intake. If you have a crappy diet and think vitamin C will save you, be careful. Overloading on vitamin C after tissue components are already oxidized could theoretically lead to further oxidation.

Crohn’s and Ulcerative Colitis

Crohn’s and ulcerative colitis patients often take vitamin C in combination with iron for anemia. That might be a bad idea, as high doses of iron worsen symptoms in Crohn’s patients. Even a single high dose of iron can cause intestinal lining oxidative damage in healthy individuals, and supplementing with quite small amounts of vitamin C and iron together leads to oxidative damage. Iron-enriched diets increase colon cancer in mice and injected vitamin C combined with iron causes ulcers in rats.

The combination of vitamin C, certain metals, and hydrogen peroxide makes up a free-radical generating process called the “Udenfriend system”. Diseased tissue, such as the intestinal tissue in bowel disorders, may contain higher levels of these components. While some in vitro studies show that the Udenfriend system is NOT your friend, others show that it doesn’t cause lipid or protein oxidation in vivo. Without a conclusive answer, it might be prudent to avoid going overboard with vitamin C and iron if you have Crohn’s or UC, especially around surgery.

Other surgeries

There are many different surgeries for many different conditions, and vitamin C hasn’t been studied for most specific examples. One type of surgery that there is evidence for is vascular surgery. In a randomized trial of vascular surgery patients, 2 grams of prophylactic vitamin C was tested for the purpose of decreasing inflammation and tissue damage. It ended up actually increasing oxidative lipid damage, which can lead to further vascular damage. Cardiac surgery can cause tissue injury when blood supply returns after a period of low oxygen. And guess what else happens when blood returns? Extra iron is released from storage, and this iron can theoretically be reduced (damaged) by vitamin C.

Conversely, vitamin C has shown promise for other surgeries. In a study of GI surgery, post-surgical oxidative stress was reduced by taking 500 mg/d of IV vitamin C. Note that IV vitamin C can lead to more than six times higher blood levels than oral intake. Since vitamin C is consumed at high rates during some surgeries, this effect seems logical, and certain patients may be very low in vitamin C before surgery and hence really need a vitamin C boost. Most often, studies combine a few antioxidants rather than testing just one, which makes singling out the effect of vitamin C difficult.

Physical therapy

In some surgeries (e.g. orthopedic surgery), surgery is only the beginning of the treatment. The rest of the treatment comes in the form of grueling, sometimes scream-inducing physical therapy that can last for weeks or months. Since muscles atrophy if a body part isn’t used much before surgery, the post-surgical period is important for muscle growth.

While vitamin C is important for joint healing, there is a small amount of evidence that vitamin C supplementation can interfere with muscle growth. And physical therapy is a combination of growing muscle, healing joints, and re-training the nervous system.

Reactive oxygen species (ROS) are not universally bad, and one of their important functions is to signal the body to increase protein synthesis as part of the mTOR pathway. Vitamin C in extremely large doses inhibits muscle growth (in rats) by quenching not just bad ROS, but helpful ROS as well. In humans the effect is uncertain, as the impact of supplemental vitamin C varies widely by study. Given the importance of vitamin C in wound healing and collagen formation, it’s likely unwise to avoid vitamin C in the post-surgical period. The takeaway may be to avoid massively overloading on antioxidants in general — large amounts of antioxidants other than vitamin C may impair muscle adaptation to exercise. And taking vitamin C to bowel tolerance directly after physical therapy may be both uncomfortable and unwise.

Conclusion

A healthy diet should support the entire endogenous oxidative system, as antioxidants often work together. So as usual, focus on getting a balance of nutrients from your diet, especially before and after surgery when nutrition is critical for healing tissue.

Vitamin C intake should be at least 500 mg/d after surgery in order to avoid the terrible pain condition RSD/CRPS. Moderate doses of vitamin C typically show benefit for oxidation, and are likely helpful before and after surgery. Only very high doses over extended periods or extremely high IV doses have been linked to adverse events like renal failure, and vitamin C studies typically only show prooxidative effects when combined with iron supplementation or in higher doses.






Curing Ankylosing Spondylitis

Posted by on January 4, 2014 112 comments

UPDATE: Steven has a new video update, to which I have added an updated commentary: Update: Attacking Ankylosing Spondylitis with PHD, November 18, 2014. FURTHER UPDATE, September 2015: Steven has created his own website with more information, www.recoveryfromas.com. Check it out!

Ankylosing spondylitis is a fearsome disease. The Mayo Clinic states:

Ankylosing spondylitis is an inflammatory disease that can cause some of the vertebrae in your spine to fuse together. This fusing makes the spine less flexible and can result in a hunched-forward posture. A severe case of ankylosing spondylitis can make it impossible for you to lift your head high enough to see forward….

Inflammation also can occur in other parts of your body — such as your eyes and bowels.

There is no cure for ankylosing spondylitis, but treatments can decrease your pain and lessen your symptoms.

But the “no cure” part is probably mistaken. Yesterday I received an email from Steven Morgan:

Hey Paul,

Your website and book saved my ass and gave me a chance to recover from Ankylosing Spondylitis, no small feat.  I made a video about it here:  http://www.youtube.com/watch?v=qvgjJTLrM3M

There was a thread on your site about high cholesterol and possible causes when going Paleo.  That thread was HUGE in my recovery….  My cholesterol fell over 200 points in two months!

Anyhow, you’re the best.  Thank you!

Cheers,

Steven

Here’s Steven’s story:

In a follow-up email, Steven elaborated:

My health is fantastic lately!  I’m still able to push the edges of what I can tolerate, and am enjoying eating butter, some white-rice based gluten-free breads, some vegetables, and occasionally cheddar cheese.  Sure beats just the 5 foods I took on my trip!  Well, to be honest, after several months of just eating coconut, cacao, pemmican, fish, and white rice, I grew quite fond of it all.  It’s amazing how your palate can change.

I gave Steven a few suggestions that I think would help anyone with AS:

  • Nutrition:
    • Vitamin A (1/4 to 1/3 lb liver per week plus spinach, sweet potatoes, yams, carrots, persimmons)
    • Vitamin D from sun and supplements.
    • Vitamin C
    • Collagen from soups and stews with joints, bones, tendons, and tripe.
    • Zinc and iodine.
  • Circadian rhythm entrainment
  • Intermittent fasting

Steven wants to share experiences with other ankylosing spondylitis sufferers; he asked me to “let folks know I’d be happy to connect; I’m especially interested in connecting with other people who have AS!” You can reach Steven by email at stevenmorganjr@gmail.com.

Conclusion

The Mayo Clinic is correct that medicine offers no cure for ankylosing spondylitis; but diet and lifestyle may do better. AS is probably an infectious condition caused by a pathogenic gut flora. Improved immune function and remodeling of the gut microbiome ought to be able to work a cure.

Steven experimented with a no-starch diet, but had better results on something more PHD like. As we’ve discussed, eating carbs is important for formation of the intestinal mucosal barrier and for proper immune function. A very low-carb diet often delivers short-term relief by starving pathogens, but it doesn’t support a probiotic gut flora and can bring long-term problems from suppressed immunity and impaired gut barrier integrity. That often leads to food sensitivities like those Steven suffered from. It’s better to obtain sufficient dietary carbohydrates to support a healthy gut. White rice is often one of the easier carbs to start with.

Thanks for writing, Steven! Your experiences and video should give hope to AS sufferers everywhere!






Toward a Proof of the PHD

Posted by on June 18, 2013 13 comments

I hope all of our readers enjoyed a happy and healthy Father’s Day.

We had two PHD-related sources of happiness this weekend. On Friday and Saturday we filmed a documentary for Korea’s SBS TV, which will air July 7 in Korea. And then, over the course of the weekend, we heard a number of positive reader stories.

I’d like to share those stories, as a warmup to telling you about about a new venture that will, we expect, create many more health successes.

Reader Results

John Parker is 70 years old and looks fantastic on PHD:

John_Parker_age_70

Well done John!

Antoniette Descisciolo-Rozean is losing weight with ease:

Week 4 Update:

Another half pound bites the dust woot woot!! 😀 😀 😀

This may not sound like a lot to many people, but I don’t have a ton of weight to lose, and I’ve NEVER lost weight as painlessly and naturally as I have on this plan!

I can absolutely do this plan for life and never feel deprived. I still have not counted one calorie, nor have not felt hunger once.

This brings my total loss at close to ten pounds on one month. I am so completely happy with this!!

My husband, who doesn’t need to lose weight, is trimming up. Though he’s lost no weight, his waist is trimming up, his chest is getting more solid, etc.

He has only cut out grains/legumes and has not changed his routine (which is naturally active), yet is experiencing these surprising improvements!

He was previously getting stiffness in his joints, and that has nearly disappeared!

Aaron Macomber has lost 53 pounds and feels ten years younger:

January to June, I’m down 53 pounds on the PHD. I also weight train for 1-1.5hrs 4 days a week, no cardio training at all. I weighed 238lbs when I started and now weigh 185, and still dropping! I’m 40 years old and I feel and look better than I did when I was 30 (now just figure out how to re-grow hair :).

The better part of the story is that the inflammation that I was constantly suffering with is reduced so much it’s incredible! My hands and feet used to ache at the end of the day, and they just don’t anymore. I used to be hot all the time, and was popping advil like they were breath mints, and I just don’t have a need for that anymore. I am still dropping 1-2lbs a week and packing on the muscle fairly fast. I will be seeing my abs for the first time in my life within the next few months and have gone from a 38-40 waist to a 32 already.

Both Antoniette and Aaron left Amazon reviews – thank you very much!

Gill is only two weeks into PHD, but has some results already:

In desperation one night I trawled the web and found your website and thought it was worth a shot. Within a matter of days of kicking gluten for good (not that I ate much wheat anyway but we scots eat a lot of oats) and starting magnesium/selenium/iodine supplements I felt 50% better. Given my deteriorating health over the preceding two years, this was a HUGE improvement. My sinuses, whilst still far from perfect, are feeling considerably better.  My energy levels, whilst still not what they used to be, have definitely picked up.  This is after a fortnight.  I am so excited that I might actually keep improving!!

June is healing:

I have started eating this style of eating introducing bone broths, organ meats, coconut oil, eliminating vegetable oils, sugar amongst other things. One big change I am finding is at 59 I was having problems with the skin on my hands, every little knock cause a a heamatoma type of bruising under the skin, an obvious sign that the collagen in my skin was lacking. Today I gave my hand a big knock & there is only a small bruise.

Also I am having less problems with my knees, so I am sold on the paleo/high fat style of eating.

I haven’t lost a lot of weight but it is stable & body fat percentage is reducing slowly. On a low fat, moderate protein diet my body fat percentage just kept going up & up.

Thank you for your book & the information it provides.

Richard Parker had inflammatory bowel disease for 35 years, now it’s gone:

I have been following the PHD for about 5 months. I had a serious flare of IBD over the Christmas holidays. For several years I had been able to control my symptoms to tolerable levels but this flare was beyond my control with my old diet. I first started with a broth diet for 2 weeks, then elimination diet before I discovered PHD. I lost 30 pounds in a month, which is mot particularly healthy before starting the PHD at the end of January. Several things truly shocked me on PHD that helped. Being able to tolerate fat, cutting down on fruit was good, elimination wheat and whole grain was good, eating egg yolks didn’t raise my cholesterol, eating liver and liking it and switching to goat dairy helped. I had been on a low fat, whole grain, yogurt, low animal protein, probiotic and Chia seed fiber diet before. The Chia seeds had been my savior to slow down the diarrhea. I still eat Chia seeds but just sprinkle them on salads. Today my digestion and elimination system is better than it has been in 35 years. My triglycerides have dropped from 153 to 72. My HDL has risen to 45 after 30 years of HDL between 27 and 35. I drink bone broth every day as I eat 3 egg yolks. The only probiotic I take now is Live Zing Salad. I also take most of the supplements recommended but take them on faith that Paul knows what he is talking about here too. I have never been able to say that I know a supplement has helped. But I wouldn’t stop anything I am doing for fear that the good changes I have experienced would end.

Bill Rafter found that PHD helped him deal with cancer:

About 6 months ago I learned that I had metastatic prostate cancer.  The treatment recommended was hormone therapy and targeted radiation.  The hormone (androgen deprivation) therapy tricks the brain into suppressing testosterone production.  The effects are a total suppression of sexual drive, hot flashes similar to those experienced by menopausal women, and the feeling that one is an old, old man.  The lack of sexual function I could deal with, and the hot flashes just seemed like a good sweat.  But, at 65 and still athletic, I found the last one particularly brutal, and questioned whether I wanted treatment at all.

A friend gave me a good book on cancer, recommending an all-out approach rather than the sequential attempts favored by most oncologists.  Nutrition was a major part of the approach.  I then trolled my friends for books on nutrition and one commented that PHD was the best he had ever read.  I am overwhelmed by what it has done for me.

After reading PHD, I immediately adopted the recommendations in full, with the exception of fasting.  I then went thru 44 radiation treatments, and never felt fatigue, a common symptom.  No more old man feelings, and no thoughts of quitting treatment.  Hot flashes are completely gone, which really puzzles the oncologists. Everyone wants to know what stopped the hot flashes.  The trouble is that because I adopted everything at once, there is no way to identify that which contributed most.  But that’s not all.

Ever since grade school I have been a nailbiter.  I knew the habit was caused by a chemical imbalance, rather than behavioral, but could never figure out what.  But since adopting PHD, my fingernails have grown to the extent that filing them is annoying.  That makes me wonder that if PHD brought my system into balance, how many other imbalanced people could also benefit.  Those people could manifest their imbalance otherwise, say with abuse of alcohol or drugs.

This reduction in cancer therapy side effects may be more significant than mere symptomatic relief. Cancer therapies generally have a very narrow margin between hurting the cancer and hurting normal tissue. A diet that enables normal cells to tolerate cancer therapies better may allow more effective doses of therapy to be used, potentially significantly improving odds of remission.

There are many other great stories on the PHD Facebook group. Our thanks to all who share their results!

Toward a Proof of the PHD

I strongly believe that PHD is, indeed, the most healthful human diet. The science is solid. Moreover, diet seems to have a large influence on health, so adopting PHD can lead to dramatic health improvements. Personal experience, and reader stories like those above, give me confidence in those claims.

But how can we prove PHD to skeptics?

Self-reported reader results don’t convince skeptics because they are an incomplete and biased sample. Those who have good results are enthusiastic and excited and take the time to report their success. Skeptics can always wonder whether there were an equal number of readers with poor results who simply didn’t report their negative experiences. To prove a diet, it is necessary to compile unbiased evidence from a complete sample.

For some time, I’ve been looking ways to generate compelling evidence. At the Ancestral Health Symposium in 2012, I organized a panel discussion (“New Technologies, New Opportunities”) looking at how new technologies such as quantified self tools with automatic data collection via Wifi could help us generate unbiased data on the effects of different diets and lifestyles.

Others in the ancestral health community are also attacking this problem. For example, Gary Taubes and collaborators have created NuSI in an effort to fund clinical trials testing the effects of low-carb diets.

Now, happily, thanks to a new partnership which I’ll announce on Thursday, we are going to have an opportunity to do a fair and unbiased test of PHD’s effectiveness. In fact, it’s already underway. At a secret location in Austin, Texas for the last four to eight weeks, a half dozen people with serious health concerns have been following the PHD diet and lifestyle advice. Every one of them has experienced health improvements. Among the results:

  • A woman who in February was walking with a cane, taking pain medications, and scheduled for knee and hip surgeries is now walking with no difficulty and has stopped her pain medications. A longtime Sjogren’s sufferer, she now has tears. She has lost two inches from her waist, is sleeping better, is happier, and has more energy.
  • A diabetic with fasting blood glucose of 160 now has fasting blood glucose in the 90s. He has lost 7 pounds and 4 inches from his waist.

I will share further details on Thursday, as we still have work to do before a formal launch and announcement. Let me just say – I am excited; I am optimistic that we can make a huge difference in the lives of a number of people; and I believe we will be able to generate convincing proof that a natural diet and lifestyle, along the lines of PHD, is the path to good health.

More coming soon!