Immunity Deep Dive Part-4

Immunity deep dive part Four

If you watch TV, especially during the day, you cannot help but notice that, seemingly every week, there is a new drug to treat plaque psoriasis. According to Drugs.com, there are now 56 drugs to treat this one condition. Plaque psoriasis is not a fatal disease, but the new drugs to treat it can kill you. I am not an anti-drug fanatic. Pharmaceutical companies create products that save lives, but this explosion of new drugs for a condition that for most people is nothing more than an embarrassment… you have to wonder what’s going on.

It starts with the pharma mindset, which I call “drugs for bugs.” This came directly from the dramatic and world-changing effects of antibiotics – which also led to the dramatic overuse of antibiotics, but that’s another story. Point is that drug companies usually start with the assumption that there is something to kill. That is not the case with autoimmune disease, but they just can’t break the habit. I imagine drug companies gathered to brainstorm an approach to autoimmune disease.
“Hmm,” says Bob, “let’s see. The immune system is attacking healthy tissue… I know! Let’s cripple the immune system.” “Brilliant!,” They all shout, and run off to their labs to develop more than 50 drugs to do just that.

If you think I’m being too snarky, watch a few ads for rheumatoid arthritis drugs, where they state that the cause of the problem is an overactive immune system, concluding that their immune-crushing drug is the obvious solution. There are two problems with this. First, of course is potentially fatal side effects associated with suppressing the immune system, ie leaving you defenseless against infections. And second, the premise is wrong. Autoimmune disease does not result from an overactive immune system. It results from a confused immune system. The solution requires a deeper understanding and a more nuanced approach. Natalie (my board-certified doctor wife) has a wonderful way of explaining this to her patients. “These drugs, she says, acting out the scenario with her hands, “are like a hammer; when all you may need is a screwdriver to make a few adjustments.”

Some of the adjustments are diet and lifestyle related, and by lifestyle, I don’t mean that lupus patients should go join a gym and take aerobics classes. But the natural tendency for people in pain is to become inactive, and that only compounds the problem. There are specific types of exercise for different conditions, and in all cases, guidance from a trained professional is important. Yoga is highly recommended for the gentle approach that incorporates a wide range of movements, as well as its stress-management benefits.

In regards to diet, the adjustments include focusing on a wide variety of fresh fruits and vegetables, wild-caught fish and hormone-free poultry; while avoiding pro-inflammatory foods like processed snack foods, saturated fats, dairy and all sugars. Switching from coffee to green tea has been shown to be helpful. Important supplements include omega-3 fatty acids from fish oil, krill or algae sources, vitamin E and most important, vitamin D. To help them remember, Natalie suggests her patients say the word, “auto-immuni-D.”

Then comes the biggest, and no doubt the easiest adjustment. Getting back to the concept of a confused immune system, it’s important to understand that immunity is controlled to a significant degree by signaling molecules called cytokines. Some, like interleukin-6 (IL-6) tell the immune system to “shoot anything that moves.” Others like IL-2, tell the immune system to only go after the bad guys. Leave healthy tissue alone. In the early 1980’s it was found that autoimmune disease is characterized by elevated IL-6 and very low levels of IL-2. Scientists knew that one of the effects of DHEA is to lower IL-6 and elevate IL-2, providing balance to the immune system. So they gave lupus patients DHEA and just about everyone improved. Every subject was able to reduce or stop their prednisone, while achieving the same level of pain control. Then they increased the dose and found that many subjects went into remission.

Was this heralded as a major breakthrough in the treatment of autoimmune disease? No, because DHEA is not a drug. It did spur a number of companies to create similar compounds (known as DHEA analogs) that could be patented. But these did not produce the same benefit as native DHEA. We now know that DHEA also acts as a natural anti-inflammatory in Rheumatoid Arthritis, and that adding DHEA can enable patients to achieve better results with a lower dose of immune-suppressing drugs.

ACTION STEPS:
If you suffer from any autoimmune disorder, instruct (do not ask) your doctor to measure your blood level of DHEA sulfate (serum DHEAS) . Most likely, you will be in double digits, when the optimum range for women is 200 to 350 mcg/dL. For men, research supports a DHEA sulfate range from 300 to 450 mcg/dL. Tell your doctor that you want to play a more active role in your care, and that includes attention to diet, exercise and supplementation with DHEA.

Now, circling back to plaque psoriasis, the unanswered question is, why use powerful immune-crushing drugs that leave you vulnerable to infection (including flu and Coronavirus)? Why use a sledgehammer when a screwdriver will do? I believe it is because the profit margins on these new drugs are astronomical, so once again, I imagine the board room scenario. Chairman: “We’re making carloads of money with these drugs for rheumatoid arthritis, lupus and MS. But there must be a way to sell even more.” Bob: “well, psoriasis has an autoimmune aspect that we can exaggerate, er, I mean highlight.” Chairman: “Excellent! get marketing on it right away!”

For a free download of Stephen Cherniske’s e-book, The Case for DHEA, go to My2048.com

References:

1. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Molecular Aspects of Medicine. Volume 33, Issue 1, February 2012, Pages 107-118. Dayong Wu, Junpeng Wang, Munkyong Pae, Simin Nikbin Meydani

2. Tumor necrosis factor inhibits conversion of DHEA sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: A prerequisite for local androgen deficiency. Arthritis & Rheumatology. 02 June 2005. https://doi.org/10.1002/art.21112 Claudia Weidler, et al.

3. Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am J Obstet Gynecol 1993; 169:1536-9. Casson PR, Anderson RN, Herrod HG, et al.

4. Dehydroepiandrosterone treatment of women with mild to moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46(11):2924-7. Chang DM, Lan JL, Lin HY, Luo SF.

5. Effects of DHEA on corticosteroid requirements of women with systemic lupus erythematosus; a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2002; 46(7):1820-9.
Petri MA, Lahita RG, Van Vollenhoven RF, et al.

6. Autoimmunity, dehydroepiandrosterone (DHEA), and stress.
Journal of Adolescent Health. 2002;30S:37–43. Kenneth E Schwartz.

7. Serum Dehydroepiandrosterone (DHEA) and DHEA Sulfate Are Negatively Correlated with Serum Interleukin-6 (IL-6), and DHEA Inhibits IL-6 Secretion from Mononuclear Cells in Man in Vitro: Possible Link between Endocrinosenescence and Immunosenescence. The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 6, 1 June 1998, Pages 2012–2017,
R. H. Straub, et al.
https://doi.org/10.1210/jcem.83.6.4876

8. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4279-84. Baulieu EE, Thomas G, Legrain et al.

9. Effects of oral DHEA on single-dose pharmacokinetics of oral prednisone and cortisol suppression in normal women. J Clin Pharmacol 2001; 41(11):1195-205. Meno-Tetang GM, Blum RA, Schwartz KE, Jusko WJ.

10. Arginine, glutamine, and DHEA reverse the immunosuppressive effect of prednisone during gut-derived sepsis Crit Care Med 1997 Jul;25(7):1207-14. Gennari R, Alexander JW.

11. Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosis: relation to other adrenal hormones. J Rheumatol 2003; 30(2):269-75. Vogl D, Falk W, Dorner M, Scholmerich J Straub RH

12. Adrenal gland hypofunction in active polymyalgia rheumatica; effect of glucocorticoid treatment on adrenal hormones and interleukin-6. J Rheumatol 2002; 29(4):748-56. Cutolo M, et al

13. Patients with refractory Crohn’s disease or ulcerative colitis respond to DHEA: a pilot study. Aliment Pharmacol Ther 2003; 17(3):409-14. Andus T, Klebl F, et al.

14. Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases – substitutes of adrenal and sex hormones. Z Rheumatol 2002; 59:Suppl 2:108-118. Straub RH, Scholmerich J, Zietz B.

15. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). 2011 May;3(5):533-42. Weiss EP, Villareal DT, Fontana L, Han DH, Holloszy JO.

 

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