Table of Contents

Herbs, spices and other plants as supplements

Many herbs and spices contain chemicals which can have immunomodulatory effects. For Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) patients, consumption of herbs and spices in meals is acceptable, but, generally speaking, MP patients should avoid herbs and spices in tablet or capsule form taken as supplements. This advisory is particularly emphatic for herbal remedies marketed as affecting the immune system.

Specific kinds

Often enough, individuals report feeling better after taking a certain herb or supplement. One of the liabilities of such consumption is that it is impossible to know how a supplement, which itself may contain hundreds of chemicals, affects the nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription. and modulates the immune response. In some cases, however, there is such evidence, so that it can be stated a bit more definitively why ingesting excess quantities of a particular herb or a supplement is, in fact, counterproductive to MP patients.

Cinnamon

Cinnamon is a popular supplement. If it lowers blood sugar, cholesterol and triglycerides by 20% as touted, it may have other effects on the body also. MP patients should limit cinnamon supplementation to avoid unknown interactions with the MP medications and the immune system. MP patients who want to improve their blood lipid profiles should try the low-carb insulin resistant diet. Cholesterol, triglycerides and even blood sugar should normalize as the inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. resolves.

Curcumin, tumeric, curry and mustard

MP patients are advised to avoid significant use of curcumin as well as its derivatives. A 2010 by Choi et al. showed that curcumin decreases androgen receptor expression in a dose-dependent manner.1) According to a 2006 Food Technology article:

Twelve scientific, peer-reviewed publications since 1999 suggest that curcumin, the major yellow pigment in tumeric, curry and mustard, may potentiate apoptosis or inhibit growth of selected cancer cells or function as a COX-2 inhibitor in several in-vitro and animal models.

Cucurmin certainly appears to impact the immune system, and therefore it is possible that high usage may increase IP in an unpredictable way. 2) 3)

Garlic

Garlic contains a chemical called allicin, which is a natural antibiotic.4) Allicin is known to inhibit bacterial cell growth. Garlic tablets taken as a supplement may interact unpredictably with MP medications and could be potentially detrimental. Eating moderate amounts of garlic as part of one's diet, however, is probably not detrimental to progress on the MP.

Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

We identified four anti-inflammatory sulfur-containing compounds from garlic, and their chemical structures were identified as Z- and E-ajoene and oxidized sulfonyl derivatives of ajoene. The sulfur compounds inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and the expression of the pro-inflammatory cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. tumor necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide (LPS)-activated macrophages. 5)

The optimum conditions for the formation of E- and Z-ajoene from garlic juice 6)

The treatment of macrophages with ajoene resulted in the activation of JNK, induction of ROS synthesis and accumulation of ROS, possibly leading to the activation of ER stress and autophagy. These results reveal the mechanism of the antimycobacterial effects of ajoene against Mtb H37Rv. Our findings might facilitate the development of novel therapies for patients with TB 7)

In vitroA technique of performing a given procedure in a controlled environment outside of a living organism - usually a laboratory., Ajoene is toxic for several tumoral cell lines, and exert an antiproliferative effect on T. cruzi and murine malaria parasites. Here we show that Ajoene strongly inhibited the proliferation induced in human lymphocytes by the mitogens phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and anti-CD3, and the capping formation induced in B lymphocytes by anti-IgM antibodies. On macrophages, Ajoene was also found to partially inhibit the lypopolysaccharide-induced production of Tumor Necrosis Factor (TNF), and to decrease the phagocytic activity of thioglycolate-elicited mouse peritoneal macrophages for IgG-opsonized, human erythrocytes. Ajoene also partially prevented the lytic effect of human and rabbit TNF on Actinomycin D-treated WEHI 164 cells. These results strongly suggest that Ajoene is a potent modulator of membrane-dependent functions of immune cells. 8)

Ajoene induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB 9)

In this study, we identified 18 essential oils (at 0.2% concentration) that are more active than 40 µM daptomycin (a persister drug control that could eradicate B. burgdorferi stationary phase cells), from which 10 essential oils stand out as having a remarkable activity even at 0.1% concentration (Table 1). Among them, garlic essential oil exhibited the best activity as shown by the lowest residual viability of B. burgdorferi at 0.1%. 10)

Grapefruit seed extract

Grapefruit seed extract is a powerful, broad-spectrum antimicrobial and anti-viral agent and is therefore contraindicated.

Grapefruit juice inhibits CYP3A4 - mediated drug metabolism drug-grapefruit interactions This interaction can lead to increases in bioavailability and corresponding increases in serum drug levels. 11)

Milk thistle

Right upper quadrant pain (which corresponds to the liver's location) is often relieved with the use of Silymarin/milk thistle, which is available in capsule form. Milk thistle is made from Silybum marianum seeds. Some researchers believe that milk thistle supplements have a detoxifying action reducing toxicity of the liver.12)

With herbs such as this, it is difficult to measure the active ingredient potency. Since it all comes from plants, they vary with growing conditions. For that reason, some brands may seem to work better than others.

For quick relief (especially when the digestive system is not working well), liquid milk thistle drops, which are usually available from a local health food store, may be helpful. Drops can be used in addition to the capsules, if needed.

The Natural Medicines Comprehensive Database describes safety and drug interactions that anyone considering its use may want to review.

Olive leaf extract

Olive leaf extract (not to be confused with olive oil) is touted as an anti-viral, especially to patients suffering from CFS. Olive leaf extract may contain vitamin D according to at least one application for patent. As a result, MP patients should not consume olive leaf extract. (The use of olive oil is not contraindicated, however.)

Carnosic acid docking into the Vitamin D Receptor

Oregano oil

Oregano oil is immunomodulatory and is it's use while on the MP is contraindicated. (The moderate use of oregano as an herb in cooking is usually OK, however.) Additionally, there has been one report of Tachycardia (fast heartbeat) and severe IP during that a short course of oregano oil (less than a week). However, it did apparently put a lung-based fungal infection into remission.

Rosemary and sage

Rosemary and sage, among other herbs, contain high levels of carnosic acid. To the right is a picture of 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. as it docks into the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response., along with a superimposition of the diterpene carnosic acid.

Carnosic Acid will displace 1,25-D (and Benicar) from the VDR in a concentration-dependent manner. It is a total antagonist of the VDR. It will therefore suppress innate immunityThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease..

The calculated affinity is high, at Ki = 54 nanomolar, about the same as the less effective ARBs and statins. As a result, only a very small amount of carnosic acid is needed to produce a negative effect.

EFA and Unsaturated oils

Unsaturated oils, especially polyunsaturates, weaken the immune system's function in ways that are similar to the damage caused by radiation, hormone imbalance, cancer, aging, or viral infections.

article by Ray Peat

Essential fatty acids (EFA) are, according to the textbooks, linoleic acid and linolenic acid, and they are supposed to have the status of “vitamins,” which must be taken in the diet to make life possible. However, we are able to synthesize our own unsaturated fats when we don't eat the “EFA,” so they are not “essential.” The term thus appears to be a misnomer. [M. E. Hanke, “Biochemistry,” Encycl. Brit. Book of the Year, 1948.]

===== Notes and comments ===== broke 2006 Food Technology article

Just another thought. I've experimented with oregano oil while on the MP. Its one of the few supplements that I've played with. I couldn't take more than a small amount once every week or two as the IP was very strong.

Carvacrol, which is highly concentrated in oregano oil, is an antibiotic efflux pump inhibitor so it may serve to greatly amplify the effects of existing abx as it prevents bacteria from pumping abx out from within their cell membranes. It is also bacteriostatic and/or bacteriocidal for a host of bacteria including staph and mycobacteria avium paratuberculosis. It also inhibits or kills fungus.

/Phillyguy

From: BIGDOG Date: 2011-03-27 22:00:50 Reply: https://www.marshallprotocol.com/reply.php?topic_id=14054

Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes

Bannwart CF, Peraçoli JC, Nakaira-Takahagi E, Peraçoli MT.

Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, Botucatu, SP, Brazil.

Abstract

Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from Silybum marianum, which has anti-inflammatory, hepatoprotective and anticarcinogenic properties. Monocytes obtained from healthy individuals were incubated with silibinin to evaluate cell viability, hydrogen peroxide (H(2)O(2)) release and tumour necrosis factor-alpha (TNF-α) production by these cells. The duration of treatment and different silibinin concentrations had no significant effect on cell viability. Monocytes showed a dose-dependent inhibitory effect on H(2)O(2) release by phorbol myristate acetate-stimulated monocytes in silibinin concentrations ranging from 6.25 to 50 µg mL(-1). Significant inhibition of TNF-α production by lipopolysaccharide-stimulated monocytes was observed at concentrations of 12.5, 50 and 100 µg mL(-1) of silibinin.

These results suggest that silibinin exerts antioxidant and anti-inflammatory properties on human monocytes through an inhibitory effect on H(2)O(2) release and on TNF-α production, respectively.

PMID: 20981616

VERY interested on the bolded section… where it inhibits inflammation and oxide production. It may work by STOPPING the natural killer behaviours and tools of our immune system.

If someone could get this whole study, I would greatly appreciate the chance to read it.

:)

From: BIGDOG Date: 2011-03-27 22:06:44 Reply: https://www.marshallprotocol.com/reply.php?topic_id=14054

Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model.

Murata N, Murakami K, Ozawa Y, KinoS***a N, Irie K, Shirasawa T, Shimizu T.

Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive impairment and the formation of senile plaques. Silymarin, an extract of milk thistle, has long been used as a medicinal herb for liver diseases. Here we report marked suppression of amyloid β-protein (Aβ) fibril formation and neurotoxicity in PC12 cells after silymarin treatment in vitro. In vivoA type of scientific study that analyzes an organism in its natural living environment. studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice. These behavioral changes were associated with a decline in Aβ oligomer production induced by silymarin intake. These results suggest that silymarin is a promising agent for the prevention of AD.

PMID: 21071836

Drug Metab Dispos. 2000 Nov;28(11):1270-3. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC. Department of Pharmaceutical Sciences School of Pharmacy, Pennsylvania, USA. rv+@pitt.edu Abstract Milk thistle extract is one of the most commonly used nontraditional therapies, particularly in Germany. Milk thistle is known to contain a number of flavonolignans. We evaluated the effect of silymarin, on the activity of various hepatic drug-metabolizing enzymes in human hepatocyte cultures. Treatment with silymarin (0.1 and 0.25 mM) significantly reduced the activity of CYP3A4 enzyme (by 50 and 100%, respectively) as determined by the formation of 6-beta-hydroxy testosterone and the activity of uridine diphosphoglucuronosyl transferase (UGT1A6/9) (by 65 and 100%, respectively) as measured by the formation of 4-methylumbelliferone glucuronide. Silymarin (0.5 mM) also significantly decreased mitochondrial respiration as determined by MTT reduction in human hepatocytes. These observations point to the potential of silymarin to impair hepatic metabolism of certain coadministered drugs in humans. Indiscriminate use of herbal products may lead to altered pharmacokinetics of certain drugs and may result in increased toxicity of certain drugs. PMID: 11038151

Herbs and Spices

I was reading pgeeks progress reports and read his comment that black pepper blocked CYP3A4 and therefore was a spice to be avoided. In checking the link he had included in another post there were 55 spices looked at. I was hoping someone could evaluate the study results presented here:

https://www.jstage.jst.go.jp/article/bpb/33/12/1977/_pdf

December 2010 Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity

Pharmacokinetic or pharmacodynamic interactions between herbal medicines or food constituents and drugs have been studied as crucial factors determining therapeutic efficacy and outcome. Most of these interactions are attributed to inhibition or induction of activity of cytochrome P450 (CYP) metabolic enzymes. Inhibition or induction of CYP enzymes by beverages, including grapefruit, pomegranate, or cranberry juice, has been well documented. Because spices are a common daily dietary component, other studies have reported inhibition of CYP activity by spices or their constituents/derivatives. However, a systematic evaluation of various spices has not been performed. In this study, we investigated effects of 55 spices on CYP3A4 and CYP2C9 activity. Cinnamon, black or white pepper, ginger, mace, and nutmeg significantly inhibited CYP3A4 or CYP2C9 activity. Furthermore, bioassay-guided fractionation of mace (Myristica fragrans) led to isolation and structural characterization of a new furan derivative (1) along with other 16 known compounds, including an acylphenol, neolignans, and phenylpropanoids. Among these isolates, (1S,2R)-1-acetoxy-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4- dimethoxyphenyl)propane (9) exhibited the most potent CYP2C9 inhibitory activity with an IC50 value compara- ble to that of sulfaphenazole, a CYP2C9 inhibitor. Compound 9 competitively inhibited CYP2C9-mediated 4'- hydroxylation of diclofenac. The inhibitory constant (Ki) of 9 was determined to be 0.037mM. Compound 9 was found to be 14-fold more potent than was sulfaphenazole. pgeek Support Team

mvanwink5 wrote: Herbs and Spices I was reading pgeeks progress reports and read his comment that black pepper blocked CYP3A4 and therefore was a spice to be avoided. In checking the link he had included in another post there were 55 spices looked at. I was hoping someone could evaluate the study results presented here: There's a chart in that paper that shows the effects of all the spices they tested on the two enzymes. There's anecdotal evidence for some of the herbs that the duration of the effects is several hours. (A google search for the name of spice + name of enzyme often pulls up discussion in other forums.)

My reaction to this has been to cut back on the amount of spices I eat, along with the frequency. (Specifically in my case I no longer put large amounts of cinnamon in yoghurt several times a day, and have spice-free porridge for breakfast.) This should have dramatically reduced any resulting enzyme inhibition.

I don't avoid spices completely or limit them to monthly or even weekly ingestion; I still eat them daily but in small amounts, and I think this is probably possible for many people. (Particularly if they de-emphasise the more active spices, and keep frequency of ingestion down to once-daily. If the information on duration of activity is reasonably accurate, this would leave the enzymes functional for 20+ hours in a 24 hour period).

But if someone who eats spicy foods daily is feeling bad on the MP, it's probably worth reducing or eliminating them to see if it helps. (Particularly if they're spices with some enzyme inhibitive activity identified in this or other papers.)

===== References =====

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