Glutamine: Reduces Inflammation and Improves Gut Health

L-glutamine is the most abundant amino acid in the human body.  Because we can make it endogenously, it is traditionally called a “non-essential amino acid”, but lately the literature seems to refer to it as a “conditionally essential amino acid” because we have learned that some people, particularly when we are under stress, require more glutamine than our bodies can produce.

Many animal studies and human clinical trials have shown that glutamine can reduce inflammation.  It seems to be especially effective at healing the mucosal lining of the intestine and restoring the hair-like villi which can be severely damage by an inflamed intestinal lining.  It is theorized that glutamine works by restoring the gut barrier and preventing the “leaky gut” syndrome which may result in chronic inflammation spreading throughout the body.

Glutamine is a very safe supplement at doses of <40 grams per day.  A normal therapeutic dose is 5-20 grams a day taken between meals in divided doses.  I generally take 5-10 grams at mid-morning and 5-10 grams at bedtime.  It is available as a capsule or powder.  At the required doses, a powder is probably more convenient and economical.  It is a fine white powder with a slightly sweet taste that is water soluble.  I mix it with water and drink it.

Glutamine is used medically to promote post surgery healing.  It is a popular sports supplement as it promotes the healing of overly stressed muscles and, taken at night on an empty stomach, can stimulate the normal pre-dawn release of human growth hormone.  Some claim that it helps with blood glucose management, but I have seen no research supporting this claim.  Presumably, reducing chronic inflammation should improve many conditions.

Are Your Dining Companions Making You Sick?

“You never dine alone,” according to biologist Jeff Gordon of the Human Gut Microbiome Initiative (HGMI). About 10-100 trillion gut microbes join you every time you eat. The reaction of your dinner guests greatly affects your health which depends not just on what you eat but also on how your intestinal microflora react to it.

Most of us think of diabetes as having a genetic component. Could it be that the genetic makeup of the microbes that have come to inhabit our gut affects us as much or more than our own DNA?

We are born with no microbes in our gut. They are all acquired after birth from our mothers, families, friends and communities. What we eat can radically alter the balance of our microbial communities, sometimes in ways that are very difficult to change. There are over 500 varieties of bacteria in our intestines, but their different attributes are not still fully understood. Science is just beginning to map the genetic code of our intestinal bacteria.

Already, a clear link has been established between obesity and our gut microflora. Fat people have very different gut microbes. Why? It seems to be a function of the bacteria we have been exposed to, what we eat and our degree of obesity. Some of the foods that I rant about in my blog can radically change your gut ecology in a rather short period of time. These changes are not easily reversed. We do know that the gut microflora changes some when people lose weight, so there is hope for improving our gut health and overall health.

Some intestinal bacteria are associated with inflammation and autoimmune disease, including diabetes. Because the role of gut bacteria in disease is complex and our understanding is still incomplete, most scientists caution against attempts to radically change gut ecology by using powerful antibiotics to eliminate intestinal bacteria and then attempting to re-colonize our guts with a healthier microbiological environment. Let me give an example of a man-made disease where tampering with the intestinal environment my lead to more serious risks.

Asthma has become much more prevalent in recent decades. After WW II, our overuse of antibiotics destroyed the common bacterium Helicobacter pylori in the guts of many people. People without H. pylori are much more likely to have asthma, allergies, and acid reflux. Writing on the ecology of human disease, one scientist has postulated that the destruction of this ancient microbe may also be a factor in the post-modern Type II diabetes and obesity epidemics. So, why not reintroduce H. pylori into our GI tracts? As it turns out, this microbe can also lead to ulcers and stomach cancer if it becomes too dominant. Tipping the scale to the other side might be even more damaging. Modern medicine’s weapons of mass microbial destruction are hardly adequate to preserve delicate balances.

Wholistic medicine has suggested that probiotics and prebiotics might help bring GI tracts ravaged by processed foods and modern drugs back into balance. Maybe, but do we really know which probiotic organisms and probiotic substances our bodies need?

Probiotics are micro-organisms which are believed to be beneficial to the human body. Yogurt with its lacto acidophilus and other live cultures has long been believed to strengthen immunity and improve health in general. Many other probiotics have been developed as nutritional supplements but our knowledge about the specific benefits of the hundreds of varieties of bacteria in our gut is currently at best partial. Anyway, yogurt tastes great and makes me feel good.

Prebiotics like fructo-oligosaccharides (FOS), inulin, and beta-glucan are believed to feed the good bacteria in the gut and improve gut health. They can be found in infant formula, nutritional supplements and some foods. I have tried them and found the short-term effects to be more embarrassing than life changing. As they ferment in your intestine, you can become quite pneumatic. One can only hope that these are the sounds of beneficial bacteria feeding well. Prebiotics, however, are not without critics. Some believe that they may also support some strains of harmful bacteria in your gut.

Here’s what we know for sure. High carbohydrate consumption, especially fructose, feed the bad bacteria and can seriously damage your gut ecology. We can also assume that healthy, fresh foods with abundant nutrients and natural fiber will improve the balance of the gut microflora.

Supplements - A Stepwise Approach

Before being diagnosed with diabetes over 14 years ago, the only supplement I was taking was a multi-vitamin. I added a couple of capsules of fish oil daily and, as I read more, I experimented with more supplements. Usually, I will start with a smaller dose and gradually build to a larger therapeutic dose. By adding new supplements one at a time gradually, I am able to ascertain how the supplements are working for me.

Only once did I have a strongly negative reaction to a supplement. That was the herbal extract ephedra which contains ephedrine, a powerful stimulant that greatly benefits weight loss but with some very negative side effects. I figured out it was not for me ... long before FDA banned it. I cannot think of any other supplement in the last two decades which has been implicated in seriously negative side effects. Supplements do not have a record of serious side effects like pharmaceuticals which have even resulted in death in rare cases. Nonetheless, sensitive people may find they have problems with mega doses of some supplements. Alpha lipoic acid is an example of an excellent supplement for diabetics that I need to be careful with. I used to take 3 x 600mg a day which I regard as the maximum reasonable dose. ALA is very acidic and I found that large 600mg capsules sometimes gave me a little heartburn. Now, I take 4 x 300mg/day with no problems.

I do take many supplements. I do believe that therapeutic doses are often mega doses. I do not think that anybody should add more than one new supplement at a time and it is best to increase dosage gradually.

Will supplements dramatically improve your health? I do hear accounts of significant improvement related to supplements, especially fish oil and Vitamin D3, but most supplements are an act of faith. I take my supplements regularly and I notice nothing. It seems as if nothing has happened -- nothing at all. No heart disease, no neuropathy, no retinopathy, no kidney disease -- nothing at all.

And that's why I take supplements.

Supplements for Diabetics

I do not know anybody who takes more supplements than me. Frankly, supplements are the realm of charlatans and weak science, so it is not easy to ascertain what really works. The industry is not nearly as profitable as the pharmaceutical industry and rarely is there commercial motivation to fund serious scientific research. I do contract manufacturing of supplements for Chinese companies at a California facility, so there's my bias ... and the source of a little bit of expertise.

My personal philosophy is that if there is convincing research suggesting a supplement may be helpful in meeting my health goals, if the supplement is not toxic or harmful at doses anywhere near what I take and it is not cost prohibitive, I will use it. I do not do this lightly. All my decisions are well researched and I urge friends to do the same. Supplements are certainly not as risky as pharmaceuticals with their many known side effects, but one must still consider the benefits and risks. I have used supplements since being diagnosed with diabetes more than 14 years ago and still have no diabetic complications ... despite some questionable lifestyle choices over the years. Maybe supplements work.

Below are the supplements which are commonly used by diabetics. I list them in priority order based on how effective I believe they are in promoting diabetic health.

Supplements which may prevent Diabetic Complications –

Omega-3 from fish oil – At least 4000mg a day of EPA & DHA omega-3 in divided doses. Reduces high triglycerides and C-reactive protein levels which are associated with the onset of heart disease and neuropathy in diabetics.

Vitamin D3 – Most diabetics are deficient in Vitamin D3 and should be tested. Generally, diabetics need to supplement with 4000-10,000 IU a day to attain optimal serum D3 levels which are known to prevent diabetes, improve insulin sensitivity, reduce heart risk and prevent many other chronic diseases.

Alpha Lipoic Acid – 600-1800mg a day in divided doses. Highly acidic, it may result in heartburn is some people. Known to prevent neuropathy and some claim it relieves symptoms of neuropathy. May lower BGs in some people. Strong inhibitor of of advanced glycation end-products (AGEs).

Biotin – 8-18mg a day in divided doses. Should be taken with Alpha Lipoic Acid as taking either individually may result in a deficiency of the other. May lower BGs in some people.

Vitamin B1 (thiamine) – 300-1200mg a day in divided doses. Mega-doses of B1 have been shown in some clinical studies to prevent diabetic neuropathy and kidney disease. As thiamine is water soluble, it quickly washes out of the body and is not very bio-available. The lipid soluble version of B1, benfotiamine is believed to be more bio-available but is relatively expensive.

Quercetin – About 500mg a day. This common flavonoid reduces levels of sorbitol which may accumulate in diabetics leading to neuropathy, nephropathy or retinopathy.

Vitamin K2 as menaquinone – 45-200mcg a day. Assists the body in effectively utilizing calcium. Prevents arterial calcification which leads to heart disease.

Vitamin B12 – 1000-2000mcg a day. Mega doses taken sublingually under the tongue as a lozenge may relieve symptoms of neuropathy and chronic fatigue. Some doctors administer it intravenously. Methylcobalamin is the form believed to be best absorbed and utilized. Those taking Metformin are more likely to have a deficiency if not supplementing.

Evening Primrose Oil – 1-4 grams a day. EPO is one of the richest sources of GLA which may prevent and/or ease the symptoms of diabetic neuropathy. EPO also lowers BGs in some people.

N-Acetyl Cysteine (NAC) – 500-1800mg a day in divided doses. NAC is a very effective inhibiter of AGE formation. Some studies found that NAC protects pancreatic beta-cells from glucotoxicity.

Lycopene – 10-20mg a day of this powerful antioxidant is very cardioprotective and inhibits the formation of AGEs. The main dietary source is cooked tomatoes, but you would need to consume an entire 6 oz. can of tomato paste to get 16mg of lycopene (and 32g of carb including 13g of fructose!), so I go for the 20mg softgels with zero carb.

Carnosine – 100-1000mg a day in 1-3 doses before meals. One of the strongest inhibitors of the advanced glycation end-products (AGEs) which lead to many complications. In the diet, this amino acid is found only in animal protein.

Supplements with may help Lower BGs –

Chromium – 200-1000mg a day may improve glucose tolerance in pre-diabetics and T2 diabetics, especially if they have a chromium deficiency. Improves lipid profile in some people.

Zinc – 15-25mg a day. Many diabetics are deficient in zinc. May improve glucose metabolism, especially in people with a known deficiency.

Magnesium – 500-600mg a day. May improve insulin sensitivity.

Vitamin D3, ALA, Biotin, EPO – Mentioned above, also may help lower BGs in some diabetics.

Supplements for General Health –

Multi-Vitamin and Mineral – Choose a product that requires at least two tablets or capsules per day to get an adequate dosage. Choose one high in B vitamins but no more than 400mg of folic acid. Vitamin A should be from betacarotene not retinol. Do not get MVMs with iron unless you have a known deficiency.

CoQ10 – 100-200mg a day, 200-300mg a day for people taking statins. Especially important for people who take statins which deplete CoQ10.

Limiting AGEs, Limiting Complications

Imagine a juicy piece of barbecued meat, marinated in a sweet BBQ sauce and grilled over flaming charcoal until it is a nice brown color with crispy pieces on the outside. Sounds good? Imagine your internal organs processed in the same way and you have a picture of the formation of advanced glycation end-products (AGEs), one of the most harmful processes associated with chronic inflammation. AGEs are the products of sugars and proteins binding together and, in the human cells, it is damage that cannot be undone. While all human tissue is subject to damage by AGEs, the lining of blood vessels in diabetics is especially sensitive leading to heart disease, long-lived nerve cells rapidly accumulate damage resulting in neuropathy, microvascular destruction leads to retinopathy and nephropathy, and AGEs are implicated in the destruction of beta cells in the pancreas. Where do these AGEs come from?

Exogenous AGEs come from your food and drink. Basically, any food preparation with high heat that involves browning is creating AGEs … browned meats, bread crust, caramel coloring in processed foods, and even my beloved dark roast coffee beans. Raw foods and foods cooked in the presence of water contain far less AGEs. Water prevents the proteins and sugars from binding. An example would be a raw chicken breast which contains a moderate amount of AGEs with 7686 units. If you boil it, you will increase the AGEs about 50%, microwaving increases AGEs two-fold, broiling increases AGEs eight-fold, and frying will multiply AGEs ten-fold. It’s not just about meat. Roasted nuts are one of the highest sources of AGEs. Healthy fresh butter has four times as much AGEs by weight as roasted meat. In general, processed meat and other processed foods are much higher in AGEs. See list of AGEs in common foods here.

Advocates of raw vegan diets point out that this way of eating has far less AGEs because raw fruits and vegetables have very little AGEs and cooked meat is never consumed. Makes sense in theory, but studies of long-term vegetarians have shown that they actually have similar or higher levels of plasma AGEs than people eating normal American diets. How can this be? It seems that vegans eat a relatively high carb diet with lots of fructose from fruits and zero carnisone or taurine from meat. This brings us to the other source of AGEs.

Endogenous AGEs are produced in the human body when sugars bind with proteins. Diabetics are especially susceptible to this process which is believed to be the source of most diabetic complications. The best way for diabetics to lower their plasma AGEs level is to lower their A1c which correlates highly with AGEs. As AGEs are a product of inflammation, they also correlate highly with CRP. Limiting carbohydrate in the diet is one of the best ways to minimize the production of AGEs. One sugar is especially deadly – fructose, which is far too abundant in the modern diet. According to Wikipedia:

Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel.

Meat, as I have explained, can be cooked into a high-AGEs food, but it is also a source of two substances that inhibit the production of AGEs in the human body. The amino acids carnosine and taurine are only available in animal protein. For this reason, a low carb diet with little fructose and abundant animal protein may be the best diet for diabetics trying to limit damaging AGEs. Ironic, as cooked meat is one of the highest sources of exogenous AGEs.

Besides carnosine and taurine, there are several nutritional supplements which reduce the production of AGEs. The vitamins benfotiamine (lipid soluble thiamine), alpha lipoic acid (ALA) and lycopene (found in tomatoes) are well known as beneficial in preventing diabetic complications. Some phytonutrients are helpful including quercetin, EGCG (green tea extract), curcumin (turmeric extract), resveratrol (found in red wine) and others.

How to reduce AGEs? Keep your blood sugar low, eat low-carb, enjoy fresh raw veggies, cook with water, limit browned foods, avoid fructose like the plague, restrict processed foods, get enough animal protein, and consider supplements to inhibit the production of AGEs.