Jiaogulan and Nitric Oxide Protocol

Dr. Eleanor Kellon, VMD, was conducting trials on Jiaogulan, which seems very promising with increasing circulation, reducing inflammation and rejuvenating older horses and lame horses.

To get involved in this study, please answer the questions below and Email Dr. Kellon

If you email Dr. Kellon and don't get an answer, email her again. Sometimes her mailbox fills up, at which point her server bounces emails...so try again! She also has email filters that automatically get re-set to overly tight security every time her software auto-updates, so sometimes emails get lost that way. Just keep trying!

The study is officially over, and with encouraging results, but Dr. Kellon is still willing to work with horse owners wanting to participate. She sent me this on 9-18-2004:

The study per se is over, but I'm still working with people who want to try Jiaogulan. The findings are described below. This summary is actually outdated already. Number of horses with good follow up is now around 150, with just over 50% becoming completely sound, 10% nonresponders (usually because of worsening of their underlying medical condition, or coffin bones that were already severely demineralized), remainder improving 1 to 2 lameness degrees initially.

Laminitis is a complicated problem that can be caused by a variety of mechanisms. Most common are disruptions of the intestinal tract severe enough to cause colic or diarrhea, systemic bacterial infections and metabolic disturbances causing decreased sensitivity to the hormone insulin (similar to diabetes). This problem is called insulin resistance and may result from genetic factors, drugs (corticosteroids), pregnancy, severe stress of any type, systemic bacterial infections or in Cushing’s disease. Symptoms of a genetic tendency toward insulin resistance include easy weight gain, fat deposits along the crest, at the tail base or elsewhere (withers/shoulders or in patches or lumps along the body), fat deposits in the hollows above the eyes. In many cases there will be more than one factor operating. For example, obviously not all pregnant mares get laminitis but if the mare had a genetic tendency toward insulin resistance to begin with the hormonal changes of pregnancy may push her over the edge.

For laminitis treatment to be successful you must:

Identify the cause
Remove the cause or treat it on an ongoing basis
Provide meticulous hoof care, often on a very frequent basis (every 2 to 3 weeks)

Failure to properly address any of these areas will give poor results. For this reason, I cannot recommend use of the Jiaogulan until all these cornerstones of proper treatment are in place. This can lead to people stating the herb is not effective and owners of horses that were in a position to benefit from it end up not trying the herb, when in reality the problem was not the Jiaogulan but rather failure to address the “big picture” correctly.

The Jiaogulan is not a cure all. There are no cure alls in laminitis. If the horse has ongoing and uncontrolled insulin resistance, it will not work. Bringing insulin resistance under control requires treatment of Cushing’s disease if that is present, and a very carefully designed diet with tight mineral balancing. There are also some herbs that will help with insulin resistance and Jiaogulan itself may have favorable effects on insulin resistance but the diet design and mineral balancing comes first. If the horse’s feet are not correctly trimmed and balanced, it will not work.

What the Jiaogulan apparently does is address problems with circulation during laminitis that can contribute to chronic pain and also delay healing in the damaged areas of the feet. Response may be dramatic and within days if the points above have been addressed.

A large number of laminitis horses have collections of blood, serum or infection in their feet that need to exit to the outside and drain. This is a very common cause of ongoing foot pain. If that is the case, the Jiaogulan may cause a temporary “worsening” as those collections are mobilizing that culminates in abscesses surfacing and draining within 1 to 2 weeks. This should be managed by frequent warm soaks of the feet, preferably with Epsom salt.

Horses and ponies respond very individually to Jiaogulan, which calls for dosage adjustments until the optimal dosage is found. Some animals also benefit from supplementation with an amino acid and specific B vitamins that support nitric oxide formation.

The field trial on laminitis in horses and ponies has been completed. Animals included in the results below had all fulfilled the criteria listed above for proper treatment. Of 118 treated with Jiaogulan, 15 horses/ponies (12.7%) failed to respond, or responded initially only to show deteriorating soundness at a later interval. In 12 of these cases, worsening of the underlying medical condition, inability to trim/shoe the feet to a state that prevented further mechanical damage, or an already severely advanced demineralization of the coffin bone were present. In three animals, the reason for poor response was unknown. 57 horses (48.3%) showed complete return to soundness at a walk within 2 days to 2 weeks of starting Jiaogulan. Some of these went through a period of abscess drainage before becoming sound. Although some of the test animals also started to spontaneously trot or even canter on their own, this was not encouraged because of the potential to damage already weakened areas of the foot. The remaining 46 horses (39%) showed obvious improvement of 1 to 2 lameness grades and were stable or continuing to improve at the end of the follow up. These horses all had pre-existing extensive damage to the feet and would require many months to a year to regrow stable laminar attachments.

Because of the huge volume of requests, I am asking a one time fee of $35 to work with people on getting their Jiaogulan dose correctly established. If you choose not to follow the other requirements for successful laminitis treatment as carefully as they need to be followed, you will be asked to state you understand this could lead to failure of Jiaogulan to help your horse or pony. If your animal has ongoing laminitis where the cause is not known, you should check for insulin resistance. If insulin resistance is found, a careful diet must be designed, with appropriate mineral supplementation. If you want me to help you with that, the fee is $100 and includes both all diet recommendations as well as help with establishing the Jiaogulan dose. You may also choose to attempt to calculate your diet requirements yourself with the help of information in the files at the Yahoo group EquineCushings. http://groups.yahoo.com/group/EquineCushings/

Eleanor M. Kellon, VMD

58 Maple Farm Rd

Ephrata PA 17522

HISTORY

Age, breed, sex:

Current level of work:

Amount of turnout or walking:

Diet:

Hay type and amount in lbs/day:

Is Hay analysis available?

Grain or other feed types and amounts/day in pounds:

List of all supplements, herbs, homeopathics, etc., dose and when started:

List of all drugs, dose and when started:

History of the problem:

Laboratory Findings and Dates:

Barefoot or shoe type:

Are pictures of feet available?

4T test: Moisture, Crude Protein, Ca, P, K, Mg, Na, ADF, Energy Calc, NDF, RFV, NFC, Cu, Fe, Zn, Mn
$26 for cored sample; $28 for un-cored sample. Wrap in plastic and mail to:
Litchfield Labs, 517-542-2915
535 Marshall St., PO Box 457, Litchfield, MI 49252 http://www.litchlab.com/ litchlab@qcnet.net

Results may be returned via email, snail mail, or fax...please specify.

General diet recommendations: mainly mixed grass hay, with an NFC (non-fiber carbohydrate) level below 15. No grain, carrots or apples for fat, cresty, inactive horses. Grain mix for foundered horses, or horses with high insulin levels:

Laminitis of many different causes is associated with acute as well as long term problems with circulation to the feet and clotting in small blood vessels. Hormonal, bacterial toxin, infectious, possibly even allergic, triggers may be involved. One of the root physiological changes that occur is production of large amounts of nitric oxide from white blood cells (the iNOS = inducible nitric oxide synthetase system) but suppression of the low level production of nitric oxide in the lining of blood vessels (the eNOS = endogenous nitric oxide synthetase system). Suppression of vascular nitric oxide production makes the vessels more prone to spasm. Commonly used anti-inflammatory agents such as phenylbutazone can help suppress the high levels of iNOS activity, but in the process also further depress the eNOS system. Production of nitric oxide by the lining of the blood vessels is also essential for the manufacture of endothelial growth factors, hormone like substances that trigger the regrowth of blood vessels into damaged areas.

Supplying nitric oxide to laminitic feet to improve circulation has been of interest for quite a long time. This is the rationale behind trying nitroglycerin patches or cream, and for supplements that contain the amino acid arginine, the precursor of nitric oxide. Unfortunately, these approaches may result in too much nitric oxide production and feed the inflammatory NO pathways as much as the beneficial vascular ones.

This trial is using the Chinese herb Jiaogulan (Gynostemma pentaphyllum). This herb appears to be very effective in supporting vascular eNOS activity while at the same time the anti-inflammatory effects curb the damaging iNOS activity.

DOSE: Recommended dose will be tailored to match the details of your history, above.

- Obviously pinker color to the mucus membranes (check mouth, vulva, conjunctiva)

- Do not use at the same time as bute or flunixine (Banamine) – these may counteract/block the effect

- Use at the same time as other adaptogenic herbs such as ginsengs may either counteract or enhance the effects, requiring dosage adjustments or discontinuation of the other herbs

- Do not use with other peripheral vasodilating drugs such as acepromazine or ACE inhibitors

- Do not use with nitroglycerin or other laminitis supplements without sending me a list of ingredients from those supplements first

- If additional pain or inflammation control is needed after first three days of therapy, contact me for safe options to combine with this herb

Initial results to date have been very encouraging but use of this herb in horses must be considered experimental. Horses appear to be very sensitive to its effects. Stay within dosage limitations and please ask anyone interested in trying this herb to contact me first so that I can review the diet, managements, supplements/drugs etc. and help with establishing a dose. Safety appears to be excellent and there are no reported toxicities or allergic reactions in people but that is always a possibility with ANY herbal, drug – even common dietary ingredients.

Finally, this is no magic bullet or quick fix. You will not get optimal results unless careful attention is also paid to correct hoof care, correct diet and supplementation, avoidance of laminitis triggers and treatment of any contributing medical conditions, such as Cushings Disease (pituitary tumor).

This group was formed for dissemination of information and sharing of experiences among owners and professionals dealing with Equine Cushings Disease. We also routinely deal with other conditions that have similarities to Cushings disease, and with laminitis in general, since that is a frequent problem of these horses. The amount of information in the files and the archived discussions is huge, and easily overwhelming. This file was put together in an effort to supply basic information/definitions.

CUSHINGS DISEASE: In the classical sense, this refers to a condition characterized by excess production of the hormone cortisol as a result of a tumor in the pituitary gland of the brain which produces high levels of the hormone ACTH. In other species, Cushings Disease just means high production of cortisol, whether due to a brain tumor or not. In other species, pituitary tumors may also produce other hormones, such as Prolactin. Studies are currently underway to determine if this is the case in horses as well.

ACTH: A hormone produced by the pituitary gland that triggers production of cortisol from the adrenal gland.

CORTISOL: A hormone produced by the adrenal gland which is released naturally during times of stress (e.g. excitement, transport, exercise, infections, trauma). When production is abnormally high and sustained, it can result in impaired immune function, resistance to insulin, electrolyte abnormalities and impaired ability to utilize protein in the diet.

INSULIN: A hormone produced by the pancreas which is needed for cells to be able to take in glucose derived from dietary carbohydrates, and to take it amino acids (proteins) to use in manufacture of enzymes, cell structures and muscle.

INSULIN RESISTANCE: A condition where the cells of the body do not respond to insulin like they should. As a result, the pancreas needs to produce more insulin than normal toget glucose and protein into the cells. This is similar to type 2 diabetes in people – the type that does not require insulin. People with insulin resistance commonly also have an elevated blood sugar (blood glucose) level, which we don’t see this in horses except in very severe cases. Insulin resistant horses will have abnormally elevated insulin though. Insulin resistance may be seen as a result of the high cortisol production in classical Cushings Disease. Might also be found in association with hypothyroidism. Ponies and “easy keeper” breeds of horses may also be genetically programmed to be insulin resistant. In that case, it probably should not be considered a disease or disorder per se but does mean you have to be careful with their diet.

PROLACTIN: A hormone produced by the pituitary gland that causes mammary development and production of milk. In people and experimental animals, some pituitary tumors.

LAMINITIS: Inflammation of the laminae – tissues that connect the coffin bone to the hoof wall inside the foot.

FOUNDER: Often used synonymously with laminitis. Some people use the term founder to indicate horses whose coffin bone has come loose from its hoof wall attachments and is displaced.

ROTATION (of the coffin bone): Movement of the coffin bone away from a parallel position with the hoof wall, so that it’s tip is pointed down toward the sole.

SINKER: A form of laminitis where the attachments of the coffin bone are weakened/lost around most of its circumference so that the whole bone sinks down inside the hoof and is putting pressure on the sole.

T4 – The largely inactive form of thyroid hormone. Most commonly done thyroid function test.

PRECUSHINGS: A term used to describe horses that may have some symptoms of Cushings disease but cannot be confirmed to have it on laboratory testing.

These vary greatly depending on the severity of the laminitis. From least severe to most they include:

- Standing with the front feet further in front of the body than normal and the hind feet further under the body than normal

- Hind end muscles tightly bunched up (shifting most of their weight to the hindquarters)

- Pulses in the arteries running over the sesamoid bones at the back of the ankle are very strong and pounding

- Appearance of rings on the feet that are close together at the toe but get progressively wider over the quarters and heels

- Abnormal fat deposits, such as a cresty neck or lumpy, cellulite-like fat at the tail base. These fat deposits will usually persist even if the horse loses weight elsewhere on his body

- Advanced symptoms include increased thirst and urination, loss of body condition, especially muscle, weakness, low energy levels

VERY nonspecific and many overlap considerably with those of insulin resistance. Slow shedding/longer than normal coat may be seen. Energy levels poor, exercise tolerance poor. Horse may be irritable and sensitive to touch. Cannot be diagnosed with any certainty by symptoms alone. Need to do blood tests.

- Abnormal hair coat (longer than normal, often curly) that does not shed out normally in the spring

- Any or all of the symptoms listed above for insulin resistance and/or hypothyroidism

BLOOD ACTH: Used to diagnose classical Cushings disease, where ACTH will be greatly elevated. Higher than normal levels may also be found in stressed horses, and possibly in aged horses, but not to the same degree.

CORTISOL RHYTHM TEST: Screening test for Cushings disease. May be both false positive and false negative results. False positives can be as high as 35%. Involves sampling twice on one day (AM and PM)

DEXAMETHASONE SUPPRESSION TEST: Screening test for Cushings disease. Involves injection of the corticosteroid drug dexamethasone. Risk of causing or worsening laminitis. Felt to be diagnostic by some veterinarians, but potential for false positives and negatives well described in other species, and may be the same in the horse. Involves collection of samples over 8 to 12 hour period

TRH STIMULATION TEST: Test for Cushings disease that is probably highly diagnostic. Involves injection of TRH, which will cause a cortisol peak in a horse with a pituitary tumor. Post-injection sample drawn at 15 to 30 minutes after TRH.

COMBINED DEXAMETHASONE SUPPRESSION/TRH STIMULATION: Test for Cushings disease – involves both tests as above.

URINARY CORTISOL:CREATININE RATIO: Test done on urine as a screen for Cushings disease. Not 100% diagnostic, but highly suggestive. More accurate than blood cortisol levels in detecting increased production of cortisol.

- Cyproheptadine – a drug which helps correct chemical imbalance in the brain by suppressing high serotonin levels,which is high with pituitary tumors.

- Pergolide (brand name Permax, generics available) – drug which helps correct chemical imbalance in the brain by boosting activity of dopamine, low with pituitary tumors. Most effective treatment but some risk of side effects.

- Vitex agnus-castus (aka Chasteberry). Herb with pharmacological activity similar to that of pergolide. Much less clinical experience with this than with pergolide but works well for some horses.

- Effective treatment also involves other measures to directly address insulin resistance, hypothyroidism and laminitis if these are present. See below.

- Most important is control of the starch and sugar level in the diet. This means eliminating ALL grains, pelleted feeds made with grains (read the ingredients on the label), supplements with a grain base, carrots, apples and access to grass. (Some stages of grass growth and/or specific grass species may be OK for some horses. Need to determine on an individual basis.)

- Feeding of grass hay only, or grass hay with some soaked beet pulp to replace grain. Some horses are OK with small amounts of rice bran as well (2 oz/lb of beet pulp).

- Analysis of hay to make sure NSC (nonstructural carbohydrate levels – primarily sugars in hays) is below 10% for any insulin resistant horse

- Analysis of mineral levels in hay to allow selection or mixing of a supplement that specifically provides what the horse needs (see other files)

- Provision of a thyroid supplement such as Thyro-L (levothyroxine sodium), at least initially

- Provision of adequate amounts of minerals in the diet to support thyroid function

- Treat Cushings Disease, insulin resistance, hypothyroidism as above to eliminate those triggers of laminitis

- Expert hoof care is CRITICAL, involves trimming to realign any mal-position of the coffin bone as a result of damage to the laminae and trimmings at frequent enough intervals to maintain this correction

Gut disturbances, and Pro-biotics

Many foundered horses have had gut disturbances resulting in a massive die-off of the benign intestinal bacteria. As these bacteria begin to decay inside the gut en masse, they generate toxins; these toxins can get into the bloodstream and trigger laminitis. Pro-biotic supplementation is always a good idea. There are two products Dr. Kellon recommends: Ration Plus and Equine Generator. Her comments on the differences between the two products:

“The difference between Ration Plus and Equine Generator is that Ration Plus contains growth factors that encourage the good bacteria, no actual bacteria in it, while the EquineGenerator contains generous amounts of live bacteria to replace populations.”

Equine Generator: http://www.bio-vet.com/equineproducts.htm

Ration Plus for Horses: http://www.rationplus.com/purchase_horse2.html

You would use Equine Generator initially if a massive die-off of intestinal bacteria is suspected, and then keep the horse on Ration Plus routinely. It doesn't hurt a thing to be on it permanently.

Dr. Kellon is currently offering
several nutrition courses online:
http://www.drkellon.com/coursedescriptions.html
NRC Plus, Nutrition as Therapy, Nutrition for Performance horses, Cushings and Insulin Resistance, Understanding Bloodwork, and Neuro & muscular Disorders.

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